diff --git a/jar/biojava-1.9.6b.jar b/jar/biojava-1.9.6b.jar new file mode 100644 index 0000000..68a3631 Binary files /dev/null and b/jar/biojava-1.9.6b.jar differ diff --git a/src/bzh/plealog/dbmirror/reader/DBUtils.java b/src/bzh/plealog/dbmirror/reader/DBUtils.java index 57bae61..efde36a 100755 --- a/src/bzh/plealog/dbmirror/reader/DBUtils.java +++ b/src/bzh/plealog/dbmirror/reader/DBUtils.java @@ -820,7 +820,7 @@ private static void analyseEmblIDLine(String idLine, IBankSequenceInfo si) { /** * Returns a SequenceInfo object from a Uniprot sequence. */ - private static IBankSequenceInfo returnUPSeqInfo(Sequence seq, boolean isEmbl) { + public static IBankSequenceInfo returnUPSeqInfo(Sequence seq, boolean isEmbl) { IBankSequenceInfo si; String value; Annotation annotItem; @@ -1075,6 +1075,12 @@ public static void retrieveUPFeatures(FeatureTable ft, Sequence seq, iter = seq.features(); while (iter.hasNext()) { feat = (Feature) iter.next(); + //Fuzzy Location from Biojava: not handled by BeeDeeM + if ((feat.getLocation().getMin()<0 || + feat.getLocation().getMin()==Integer.MAX_VALUE || + feat.getLocation().getMax()<0 || + feat.getLocation().getMax()==Integer.MAX_VALUE)) + continue; strLoc = gff.formatLocation(feat); fLoc = analyseFeatureLocation(strLoc, id != null ? id : "seqId", -adjust); if (fLoc == null) @@ -1139,7 +1145,7 @@ private static String cutSequence(String seq, int from, int to) { * * @return a feature table. */ - private static FeatureTable returnUPFeatureTable(Sequence seq, String id, + public static FeatureTable returnUPFeatureTable(Sequence seq, String id, int start, int stop, boolean remap) { FeatureTable ft; diff --git a/src/test/unit/AllTests.java b/src/test/unit/AllTests.java index 5fc486b..52b2c35 100644 --- a/src/test/unit/AllTests.java +++ b/src/test/unit/AllTests.java @@ -47,7 +47,8 @@ PAnnotateBlastResultTest.class, CmdLineQueryTest.class, PFTPLoaderTest.class, - BankJsonTest.class + BankJsonTest.class, + UniprotFormatTest.class }) public class AllTests { diff --git a/src/test/unit/UniprotFormatTest.java b/src/test/unit/UniprotFormatTest.java new file mode 100644 index 0000000..f77d56d --- /dev/null +++ b/src/test/unit/UniprotFormatTest.java @@ -0,0 +1,306 @@ +/* Copyright (C) 2019-2022 Patrick G. Durand + * + * This program is free software: you can redistribute it and/or modify + * it under the terms of the GNU Affero General Public License as published by + * the Free Software Foundation, either version 3 of the License, or + * (at your option) any later version. + * + * You may obtain a copy of the License at + * + * https://www.gnu.org/licenses/agpl-3.0.txt + * + * This program is distributed in the hope that it will be useful, + * but WITHOUT ANY WARRANTY; without even the implied warranty of + * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the + * GNU Affero General Public License for more details. + */ +package test.unit; + +import static org.junit.Assert.assertEquals; +import static org.junit.Assert.assertNotNull; +import static org.junit.Assert.assertTrue; + +import java.io.BufferedReader; +import java.io.File; +import java.io.FileReader; +import java.text.MessageFormat; +import java.util.Enumeration; +import java.util.HashSet; +import java.util.Iterator; + +import org.biojava.bio.seq.Feature; +import org.biojava.bio.seq.Sequence; +import org.biojava.bio.seq.SequenceIterator; +import org.biojava.bio.seq.io.SeqIOTools; +import org.junit.After; +import org.junit.AfterClass; +import org.junit.Before; +import org.junit.BeforeClass; +import org.junit.Test; + +import bzh.plealog.bioinfo.api.data.feature.FeatureTable; +import bzh.plealog.bioinfo.data.sequence.IBankSequenceInfo; +import bzh.plealog.dbmirror.reader.DBUtils; + +@SuppressWarnings("deprecation") +public class UniprotFormatTest { + // change in Uniprot data format (Feature Table) introduce in release 2019_12 + // see https://www.uniprot.org/news/2019/12/18/release#text%5Fft + // We use an update release of Biojava legacy 1.9 from + // https://github.com/pgdurand/biojava-legacy.git + + private static String up_file_new = "019R_FRG3G_nf.dat"; + private static int expect_feat_new = 12; + + @SuppressWarnings("unused") + private static String up_file_old = "019R_FRG3G_of.dat"; + @SuppressWarnings("unused") + private static int expect_feat_old = 8; + + private static String current_file = up_file_new; + private static int current_feats = expect_feat_new; + + private static final boolean TEST_ENTIRE_SWISS = false; + private static String SWISS_PATH = + "/tmp/biobanks/p/Uniprot_SwissProt/current/Uniprot_SwissProt/uniprot_sprot.dat"; + private static final boolean DISPLAY_ID = true; + + private static HashSet featBiojavaLocRef; + + @BeforeClass + public static void setUpBeforeClass() throws Exception { + UtilsTest.configureApp(); + featBiojavaLocRef = new HashSet(); + featBiojavaLocRef.add("chain-1-129-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("mod_res-1-1-/IsoformId=\"P68250-2\" /note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("chain-2 147 483 647-245-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("chain-31-137-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("chain-1-55-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("transit-1--2 147 483 648-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("chain-69-255-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("chain-1-24-/note=\"toto\" /evidence=\"titi\""); + featBiojavaLocRef.add("signal-1--2 147 483 648-/note=\"toto\" /evidence=\"titi\""); + } + + @AfterClass + public static void tearDownAfterClass() throws Exception { + } + + @Before + public void setUp() throws Exception { + } + + @After + public void tearDown() throws Exception { + } + public static final MessageFormat FEATURE_FORMAT = new MessageFormat("{0}-{1}-{2}-{3}"); + private String featureToString(Feature feat) { + String f = FEATURE_FORMAT.format(new Object[] { + feat.getType().toLowerCase(), + feat.getLocation().getMin(), + feat.getLocation().getMax(), + feat.getAnnotation().getProperty("swissprot.featureattribute").toString().trim()}); + //System.out.println(" " + f); + return f; + } + // Method used to encode BeeDeeM Feature properties in order to compare them with BioJava ones + private String getDescription(bzh.plealog.bioinfo.api.data.feature.Feature feat) { + Enumeration enumQ = feat.enumQualifiers(); + while(enumQ.hasMoreElements()) { + bzh.plealog.bioinfo.api.data.feature.Qualifier qual = enumQ.nextElement(); + if (qual.getName().equalsIgnoreCase(feat.getKey())) { + return qual.getValue(); + } + } + return "?"; + } + //Method used to encode BioJava Feature properties in order to compare them with BeeDeeM ones + private String featureToString(bzh.plealog.bioinfo.api.data.feature.Feature feat) { + String f = FEATURE_FORMAT.format(new Object[] { + feat.getKey(), + feat.getFrom(), + feat.getTo(), + getDescription(feat)}); + //System.out.println(" " + f); + return f; + } + + @SuppressWarnings("rawtypes" ) + private void testSequence(Sequence seq, int curFeats) { + IBankSequenceInfo si; + FeatureTable ft; + HashSet featBiojava, featBeeDeeM; + assertNotNull(seq); + if (DISPLAY_ID) { + System.out.println("> " + seq.getName()); + } + Iterator iterF = seq.features(); + featBiojava = new HashSet(); + while (iterF.hasNext()) { + Feature feat = (Feature) iterF.next(); + if ( + !(feat.getLocation().getMin()<0 || + feat.getLocation().getMin()==Integer.MAX_VALUE || + feat.getLocation().getMax()<0 || + feat.getLocation().getMax()==Integer.MAX_VALUE) + ) { + //BeeDeeM does not handle fuzzy locations + featBiojava.add(featureToString(feat)); + } + } + if (curFeats!=-1) { + assertEquals(featBiojava.size(), curFeats); + } + // get sequence info + si = DBUtils.returnUPSeqInfo(seq, false); + // get feature table; BeeDeeM always add source and protein features w/t what Biojava does provide + // (source contains taxon info, protein contains protein description and db_xrefs) + ft = DBUtils.returnUPFeatureTable(seq, si.getId(), 0, 0, false); + + assertEquals(featBiojava.size(), ft.features()-2); + Enumeration enumF = ft.enumFeatures(); + featBeeDeeM = new HashSet(); + while(enumF.hasMoreElements()) { + bzh.plealog.bioinfo.api.data.feature.Feature feat = enumF.nextElement(); + featBeeDeeM.add(featureToString(feat)); + } + for(String f : featBeeDeeM) { + if (featBiojava.contains(f)) { + featBiojava.remove(f); + } + } + assertEquals(featBiojava.size(), 0); + } + + @Test + public void testUniprotFormatChange() { + System.out.println(">> testUniprotFormatChange"); + // Uniprot format manual: https://web.expasy.org/docs/userman.html + // Test Uniprot data format, i.e. Feature Table encoded as: + //FT DOMAIN 128 409 Protein kinase. + //FT NP_BIND 134 142 ATP (By similarity). + // From Uniprot release 76 and above, Features are encoded as: + //FT CHAIN 1..851 + //FT /note="Putative serine/threonine-protein kinase 019R" + //FT /id="PRO_0000410576" + + String file = UtilsTest.getTestFilePath("databank", "uniprot", current_file); + try (BufferedReader reader = new BufferedReader(new FileReader(file))) { + Sequence seq; + + + // read the Uniprot File + SequenceIterator iter = SeqIOTools.readSwissprot(reader); + assertTrue(iter.hasNext()); + seq = iter.nextSequence(); + testSequence(seq, current_feats); + } catch (Exception ex) { + System.err.println("unable to read UniProt file: " + file + ": " + ex); + } + } + + @Test + public void testLargeFile() { + System.out.println(">> testLargeFile"); + + String file = UtilsTest.getTestFilePath("databank", "uniprot", "uniprot_new.dat"); + try (BufferedReader reader = new BufferedReader(new FileReader(file))) { + Sequence seq; + // read the Uniprot File + SequenceIterator iter = SeqIOTools.readSwissprot(reader); + while(iter.hasNext()) { + seq = iter.nextSequence(); + testSequence(seq, -1); + } + } catch (Exception ex) { + System.err.println("unable to read UniProt file: " + file + ": " + ex); + } + } + + @Test + public void testUniqueFile() { + //specific test to debug entire SwissProt + //Use this URL to get specifi entry: + // https://www.uniprot.org/uniprot/C0HLM8.txt + System.out.println(">> testUniqueFile"); + String file = UtilsTest.getTestFilePath("databank", "uniprot", "single-up-test.dat"); + try (BufferedReader reader = new BufferedReader(new FileReader(file))) { + Sequence seq; + // read the Uniprot File + SequenceIterator iter = SeqIOTools.readSwissprot(reader); + while(iter.hasNext()) { + seq = iter.nextSequence(); + testSequence(seq, -1); + } + } catch (Exception ex) { + System.err.println("unable to read UniProt file: " + file + ": " + ex); + } + } + + @SuppressWarnings("rawtypes") + @Test + public void testAllLocationTypes() { + //specific test to check all types of Uniprot FT locations + System.out.println(">> testUniqueFile"); + String file = UtilsTest.getTestFilePath("databank", "uniprot", "locations-up-test.dat"); + try (BufferedReader reader = new BufferedReader(new FileReader(file))) { + HashSet featBiojava; + Sequence seq; + // read the Uniprot File + SequenceIterator iter = SeqIOTools.readSwissprot(reader); + while(iter.hasNext()) { + seq = iter.nextSequence(); + /**/ + + assertNotNull(seq); + if (DISPLAY_ID) { + System.out.println("> " + seq.getName()); + } + Iterator iterF = seq.features(); + featBiojava = new HashSet(); + while (iterF.hasNext()) { + Feature feat = (Feature) iterF.next(); + //BeeDeeM does not handle fuzzy locations + featBiojava.add(featureToString(feat)); + } + assertEquals(featBiojava.size(), 9); + for (String str : featBiojavaLocRef) { + featBiojava.remove(str); + } + assertEquals(featBiojava.size(), 0); + } + } catch (Exception ex) { + System.err.println("unable to read UniProt file: " + file + ": " + ex); + } + } + + @Test + public void testEntireSwissProt() { + if (!TEST_ENTIRE_SWISS) + return; + System.out.println(">> testEntireSwissProt"); + + //not really a bad error + if (new File(SWISS_PATH).exists() == false) { + System.err.println("File not found: " + SWISS_PATH); + return; + } + int counter=0; + try (BufferedReader reader = new BufferedReader(new FileReader(SWISS_PATH))) { + Sequence seq; + // read the Uniprot File + SequenceIterator iter = SeqIOTools.readSwissprot(reader); + while(iter.hasNext()) { + seq = iter.nextSequence(); + testSequence(seq, -1); + counter++; + if (counter % 10000 == 0) { + System.out.println("Sequences reviewed: " + counter); + } + } + } catch (Exception ex) { + System.err.println("unable to read UniProt file: " + SWISS_PATH + ": " + ex); + } + System.out.println("Total Sequences: " + counter); + } +} diff --git a/tests/junit/databank/uniprot/019R_FRG3G_nf.dat b/tests/junit/databank/uniprot/019R_FRG3G_nf.dat new file mode 100644 index 0000000..70e3e67 --- /dev/null +++ b/tests/junit/databank/uniprot/019R_FRG3G_nf.dat @@ -0,0 +1,119 @@ +ID 019R_FRG3G Reviewed; 851 AA. +AC Q6GZV6; +DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot. +DT 19-JUL-2004, sequence version 1. +DT 23-FEB-2022, entry version 82. +DE RecName: Full=Putative serine/threonine-protein kinase 019R; +DE EC=2.7.11.1; +GN ORFNames=FV3-019R; +OS Frog virus 3 (isolate Goorha) (FV-3). +OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Megaviricetes; +OC Pimascovirales; Iridoviridae; Alphairidovirinae; Ranavirus. +OX NCBI_TaxID=654924; +OH NCBI_TaxID=30343; Dryophytes versicolor (chameleon treefrog). +OH NCBI_TaxID=8404; Lithobates pipiens (Northern leopard frog) (Rana pipiens). +OH NCBI_TaxID=45438; Lithobates sylvaticus (Wood frog) (Rana sylvatica). +OH NCBI_TaxID=8316; Notophthalmus viridescens (Eastern newt) (Triturus viridescens). +RN [1] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RX PubMed=15165820; DOI=10.1016/j.virol.2004.02.019; +RA Tan W.G., Barkman T.J., Gregory Chinchar V., Essani K.; +RT "Comparative genomic analyses of frog virus 3, type species of the genus +RT Ranavirus (family Iridoviridae)."; +RL Virology 323:70-84(2004). +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- +CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- +CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, +CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- +CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, +CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; +CC EC=2.7.11.1; +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein +CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AY548484; AAT09678.1; -; Genomic_DNA. +DR RefSeq; YP_031597.1; NC_005946.1. +DR PRIDE; Q6GZV6; -. +DR GeneID; 2947739; -. +DR KEGG; vg:2947739; -. +DR Proteomes; UP000008770; Genome. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. +DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:RHEA. +DR InterPro; IPR014901; 2-cysteine_adaptor. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR017441; Protein_kinase_ATP_BS. +DR InterPro; IPR008271; Ser/Thr_kinase_AS. +DR Pfam; PF08793; 2C_adapt; 5. +DR Pfam; PF00069; Pkinase; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. +PE 3: Inferred from homology; +KW ATP-binding; Kinase; Nucleotide-binding; Reference proteome; +KW Serine/threonine-protein kinase; Transferase. +FT ACT_SITE 608 +FT /note="Proton acceptor" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, +FT ECO:0000255|PROSITE-ProRule:PRU10027" +FT CHAIN 1..851 +FT /note="Putative serine/threonine-protein kinase 019R" +FT /id="PRO_0000410576" +FT DOMAIN 456..851 +FT /note="Protein kinase" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT NP_BIND 462..470 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT REGION 1..24 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 61..91 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 104..160 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 190..216 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 340..400 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT COMPBIAS 198..212 +FT /note="Basic residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT COMPBIAS 341..380 +FT /note="Polar residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT BINDING 485 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +SQ SEQUENCE 851 AA; 92929 MW; 5FB497EDDDD37D89 CRC64; + MATNYCDEFE RNPTRNPRTG RTIKRGGPVF RALERECSDG AARVFPAAAV RGAAAARAAS + PRVAAASPCP EFARDPTRNP RTGRPIKRGG PVFRALEREC ADYGGASPRR VSPARAFPNR + RVSPARRQSP AEAAEASPCP EFARDPTRNP RTGRTIKRGG PTYRALEAEC ADYGRLSPIR + SPWSDWSSTG LSPFRSHMRK SPARRSPARR SPARRSLARY TEHLTSDSET EVDYDARNVI + RSQVGPGGVC ERFAADPTRN PVTGSPLSRN DPLYTDLMEI CKGYPDTPLT KSLTGEGTDD + DTCEAFCRDP TRNPVTGQKM RRNGIEYQMF AEECDCSGIS RPSGVSRTSG TSGSSGSSAS + SRPPNSFEAP GASSRPPNSF EASGAARVPG TPSVSRGEPR WMSSISTRHN YDESNPMSVA + FRLRHVKDIR KFLRTVRPGR SGFCATDKGG WLGSAAVSDN VIGQGSWGSV HMVKFRDFPE + EFVVKEAVLM SVSEKHRYKP TVVWDEWAAG SVPDEVVVNN MVTEIAATGM TPFVPLTAGA + GACDSCNPQL LEKAAKVTKC YLQAMEAADF SLDRVLPTMS PDQAASALAQ ILLGLQSLQT + TLGIMHNDIK AHNILVKRVP PGGYWKVTDS FNGQVFYIPN EGYLCMLADY GVVRLVKPAV + GMDTLYGTRN ARFVPRDVGR WGKGAGTEYV VTPIRSKISV VVRGGRFVGV EPNKAVRYWK + NTDTSKVGDV ITTNNVFYMG YDIEPDMQVQ LDDTNSFPVW ESRGDVADCV RTFVGGKRAS + QPGFHRLFYK KTGSAWEKAA ETVAKQNPLF SGFTLDGSGL KYIRAATACA YIFPGMAVPR + PGEREIESFT M +// diff --git a/tests/junit/databank/uniprot/019R_FRG3G_of.dat b/tests/junit/databank/uniprot/019R_FRG3G_of.dat new file mode 100644 index 0000000..eba4781 --- /dev/null +++ b/tests/junit/databank/uniprot/019R_FRG3G_of.dat @@ -0,0 +1,92 @@ +ID 019R_FRG3G Reviewed; 851 AA. +AC Q6GZV6; +DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot. +DT 19-JUL-2004, sequence version 1. +DT 13-NOV-2019, entry version 75. +DE RecName: Full=Putative serine/threonine-protein kinase 019R; +DE EC=2.7.11.1; +GN ORFNames=FV3-019R; +OS Frog virus 3 (isolate Goorha) (FV-3). +OC Viruses; Iridoviridae; Alphairidovirinae; Ranavirus. +OX NCBI_TaxID=654924; +OH NCBI_TaxID=30343; Dryophytes versicolor (chameleon treefrog). +OH NCBI_TaxID=8404; Lithobates pipiens (Northern leopard frog) (Rana pipiens). +OH NCBI_TaxID=8316; Notophthalmus viridescens (Eastern newt) (Triturus viridescens). +OH NCBI_TaxID=45438; Rana sylvatica (Wood frog). +RN [1] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RX PubMed=15165820; DOI=10.1016/j.virol.2004.02.019; +RA Tan W.G., Barkman T.J., Gregory Chinchar V., Essani K.; +RT "Comparative genomic analyses of frog virus 3, type species of the +RT genus Ranavirus (family Iridoviridae)."; +RL Virology 323:70-84(2004). +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- +CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- +CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; +CC EC=2.7.11.1; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- +CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, +CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; +CC EC=2.7.11.1; +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr +CC protein kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. +CC ----------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC ----------------------------------------------------------------------- +DR EMBL; AY548484; AAT09678.1; -; Genomic_DNA. +DR RefSeq; YP_031597.1; NC_005946.1. +DR GeneID; 2947739; -. +DR KEGG; vg:2947739; -. +DR Proteomes; UP000008770; Genome. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. +DR InterPro; IPR014901; 2-cysteine_adaptor. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR017441; Protein_kinase_ATP_BS. +DR InterPro; IPR008271; Ser/Thr_kinase_AS. +DR Pfam; PF08793; 2C_adapt; 5. +DR Pfam; PF00069; Pkinase; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. +PE 3: Inferred from homology; +KW ATP-binding; Complete proteome; Kinase; Nucleotide-binding; +KW Reference proteome; Serine/threonine-protein kinase; Transferase. +FT CHAIN 1 851 Putative serine/threonine-protein kinase +FT 019R. +FT /FTId=PRO_0000410576. +FT DOMAIN 456 851 Protein kinase. {ECO:0000255|PROSITE- +FT ProRule:PRU00159}. +FT NP_BIND 462 470 ATP. {ECO:0000255|PROSITE- +FT ProRule:PRU00159}. +FT COMPBIAS 53 59 Poly-Ala. +FT ACT_SITE 608 608 Proton acceptor. {ECO:0000255|PROSITE- +FT ProRule:PRU00159, ECO:0000255|PROSITE- +FT ProRule:PRU10027}. +FT BINDING 485 485 ATP. {ECO:0000255|PROSITE- +FT ProRule:PRU00159}. +SQ SEQUENCE 851 AA; 92929 MW; 5FB497EDDDD37D89 CRC64; + MATNYCDEFE RNPTRNPRTG RTIKRGGPVF RALERECSDG AARVFPAAAV RGAAAARAAS + PRVAAASPCP EFARDPTRNP RTGRPIKRGG PVFRALEREC ADYGGASPRR VSPARAFPNR + RVSPARRQSP AEAAEASPCP EFARDPTRNP RTGRTIKRGG PTYRALEAEC ADYGRLSPIR + SPWSDWSSTG LSPFRSHMRK SPARRSPARR SPARRSLARY TEHLTSDSET EVDYDARNVI + RSQVGPGGVC ERFAADPTRN PVTGSPLSRN DPLYTDLMEI CKGYPDTPLT KSLTGEGTDD + DTCEAFCRDP TRNPVTGQKM RRNGIEYQMF AEECDCSGIS RPSGVSRTSG TSGSSGSSAS + SRPPNSFEAP GASSRPPNSF EASGAARVPG TPSVSRGEPR WMSSISTRHN YDESNPMSVA + FRLRHVKDIR KFLRTVRPGR SGFCATDKGG WLGSAAVSDN VIGQGSWGSV HMVKFRDFPE + EFVVKEAVLM SVSEKHRYKP TVVWDEWAAG SVPDEVVVNN MVTEIAATGM TPFVPLTAGA + GACDSCNPQL LEKAAKVTKC YLQAMEAADF SLDRVLPTMS PDQAASALAQ ILLGLQSLQT + TLGIMHNDIK AHNILVKRVP PGGYWKVTDS FNGQVFYIPN EGYLCMLADY GVVRLVKPAV + GMDTLYGTRN ARFVPRDVGR WGKGAGTEYV VTPIRSKISV VVRGGRFVGV EPNKAVRYWK + NTDTSKVGDV ITTNNVFYMG YDIEPDMQVQ LDDTNSFPVW ESRGDVADCV RTFVGGKRAS + QPGFHRLFYK KTGSAWEKAA ETVAKQNPLF SGFTLDGSGL KYIRAATACA YIFPGMAVPR + PGEREIESFT M +// diff --git a/tests/junit/databank/uniprot/locations-up-test.dat b/tests/junit/databank/uniprot/locations-up-test.dat new file mode 100644 index 0000000..1299feb --- /dev/null +++ b/tests/junit/databank/uniprot/locations-up-test.dat @@ -0,0 +1,174 @@ +ID 1433B_BOVIN Reviewed; 246 AA. +AC P68250; P29358; Q0VCL1; +DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot. +DT 23-JAN-2007, sequence version 2. +DT 23-FEB-2022, entry version 120. +DE RecName: Full=14-3-3 protein beta/alpha; +DE AltName: Full=Protein kinase C inhibitor protein 1; +DE Short=KCIP-1; +DE Contains: +DE RecName: Full=14-3-3 protein beta/alpha, N-terminally processed; +GN Name=YWHAB; +OS Bos taurus (Bovine). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; +OC Bovinae; Bos. +OX NCBI_TaxID=9913; +RN [1] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). +RC STRAIN=Hereford; TISSUE=Fetal pons; +RG NIH - Mammalian Gene Collection (MGC) project; +RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. +RN [2] +RP PROTEIN SEQUENCE OF 2-246. +RX PubMed=1671102; DOI=10.1016/0022-2836(91)90616-e; +RA Isobe T., Ichimura T., Sunaya T., Okuyama T., Takahashi N., Kuwano R., +RA Takahashi Y.; +RT "Distinct forms of the protein kinase-dependent activator of tyrosine and +RT tryptophan hydroxylases."; +RL J. Mol. Biol. 217:125-132(1991). +RN [3] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). +RA Jones J.M., Niikura T., Pinke R.M., Guo W., Molday L., Leykam J., +RA McConnell D.G.; +RT "Expression of 14-3-3 proteins in bovine retinal photoreceptors."; +RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. +RN [4] +RP FUNCTION. +RX PubMed=7931346; DOI=10.1046/j.1471-4159.1994.63051908.x; +RA Tanji M., Horwitz R., Rosenfeld G., Waymire J.C.; +RT "Activation of protein kinase C by purified bovine brain 14-3-3: comparison +RT with tyrosine hydroxylase activation."; +RL J. Neurochem. 63:1908-1916(1994). +CC -!- FUNCTION: Adapter protein implicated in the regulation of a large +CC spectrum of both general and specialized signaling pathways. Binds to a +CC large number of partners, usually by recognition of a phosphoserine or +CC phosphothreonine motif. Binding generally results in the modulation of +CC the activity of the binding partner. Negative regulator of +CC osteogenesis. Blocks the nuclear translocation of the phosphorylated +CC form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on +CC cyclin D1 expression resulting in blockage of neuronal apoptosis +CC elicited by SRPK2. Negative regulator of signaling cascades that +CC mediate activation of MAP kinases via AKAP13. +CC {ECO:0000250|UniProtKB:P31946, ECO:0000269|PubMed:7931346}. +CC -!- SUBUNIT: Homodimer (By similarity). Interacts with SAMSN1 and PRKCE (By +CC similarity). Interacts with AKAP13. Interacts with SSH1 and +CC TORC2/CRTC2. Interacts with ABL1; the interaction results in +CC cytoplasmic location of ABL1 and inhibition of cABL-mediated apoptosis. +CC Interacts with ROR2 (dimer); the interaction results in phosphorylation +CC of YWHAB on tyrosine residues. Interacts with GAB2. Interacts with YAP1 +CC (phosphorylated form). Interacts with the phosphorylated (by AKT1) form +CC of SRPK2. Interacts with PKA-phosphorylated AANAT. Interacts with +CC MYO1C. Interacts with SIRT2 (By similarity). Interacts with the 'Thr- +CC 369' phosphorylated form of DAPK2 (By similarity). Interacts with +CC PI4KB, TBC1D22A and TBC1D22B. Interacts with the 'Ser-1134' and 'Ser- +CC 1161' phosphorylated form of SOS1 (By similarity). Interacts (via +CC phosphorylated form) with YWHAB; this interaction occurs in a protein +CC kinase AKT1-dependent manner (By similarity). Interacts with SLITRK1. +CC Interacts with SYNPO2 (phosphorylated form); YWHAB competes with ACTN2 +CC for interaction with SYNPO2 (By similarity). Interacts with RIPOR2 (via +CC phosphorylated form); this interaction occurs in a chemokine-dependent +CC manner and does not compete for binding of RIPOR2 with RHOA nor blocks +CC inhibition of RIPOR2-mediated RHOA activity (By similarity). Interacts +CC with MARK2 and MARK3 (By similarity). Interacts with TESK1; the +CC interaction is dependent on the phosphorylation of TESK1 'Ser-439' and +CC inhibits TESK1 kinase activity (By similarity). Interacts with MEFV (By +CC similarity). {ECO:0000250|UniProtKB:P31946, +CC ECO:0000250|UniProtKB:Q9CQV8}. +CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31946}. +CC Melanosome {ECO:0000250|UniProtKB:P31946}. +CC -!- ALTERNATIVE PRODUCTS: +CC Event=Alternative initiation; Named isoforms=2; +CC Comment=It is uncertain whether isoform Short is produced by +CC alternative initiation or another biological event.; +CC Name=Long; +CC IsoId=P68250-1; Sequence=Displayed; +CC Name=Short; +CC IsoId=P68250-2; Sequence=VSP_018631; +CC -!- PTM: The alpha, brain-specific form differs from the beta form in being +CC phosphorylated. Phosphorylated on Ser-60 by protein kinase C delta type +CC catalytic subunit in a sphingosine-dependent fashion. {ECO:0000250}. +CC -!- SIMILARITY: Belongs to the 14-3-3 family. {ECO:0000305}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; BC120112; AAI20113.1; -; mRNA. +DR EMBL; AF043736; AAC02090.1; -; mRNA. +DR PIR; S13467; S13467. +DR RefSeq; NP_777219.2; NM_174794.2. +DR SMR; P68250; -. +DR STRING; 9913.ENSBTAP00000022411; -. +DR iPTMnet; P68250; -. +DR PaxDb; P68250; -. +DR PeptideAtlas; P68250; -. +DR PRIDE; P68250; -. +DR GeneID; 286863; -. +DR KEGG; bta:286863; -. +DR CTD; 7529; -. +DR eggNOG; KOG0841; Eukaryota. +DR HOGENOM; CLU_058290_1_0_1; -. +DR InParanoid; P68250; -. +DR OrthoDB; 1176818at2759; -. +DR TreeFam; TF102003; -. +DR Proteomes; UP000009136; Unplaced. +DR GO; GO:0005737; C:cytoplasm; ISS:AgBase. +DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. +DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:AgBase. +DR GO; GO:0019904; F:protein domain specific binding; ISS:AgBase. +DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB. +DR GO; GO:0034613; P:cellular protein localization; IBA:GO_Central. +DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB. +DR GO; GO:0006605; P:protein targeting; ISS:AgBase. +DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. +DR Gene3D; 1.20.190.20; -; 1. +DR InterPro; IPR000308; 14-3-3. +DR InterPro; IPR023409; 14-3-3_CS. +DR InterPro; IPR036815; 14-3-3_dom_sf. +DR InterPro; IPR023410; 14-3-3_domain. +DR PANTHER; PTHR18860; PTHR18860; 1. +DR Pfam; PF00244; 14-3-3; 1. +DR PIRSF; PIRSF000868; 14-3-3; 1. +DR PRINTS; PR00305; 1433ZETA. +DR SMART; SM00101; 14_3_3; 1. +DR SUPFAM; SSF48445; SSF48445; 1. +DR PROSITE; PS00796; 1433_1; 1. +DR PROSITE; PS00797; 1433_2; 1. +PE 1: Evidence at protein level; +KW Acetylation; Alternative initiation; Cytoplasm; Direct protein sequencing; +KW Isopeptide bond; Nitration; Phosphoprotein; Reference proteome; +KW Ubl conjugation. +FT MOD_RES P68250-2:1 +FT /note="toto" +FT /evidence="titi" +FT TRANSIT 1..? +FT /note="toto" +FT /evidence="titi" +FT CHAIN ?..245 +FT /note="toto" +FT /evidence="titi" +FT SIGNAL <1..? +FT /note="toto" +FT /evidence="titi" +FT CHAIN 31..?137 +FT /note="toto" +FT /evidence="titi" +FT CHAIN ?69..255 +FT /note="toto" +FT /evidence="titi" +FT CHAIN 1..>24 +FT /note="toto" +FT /evidence="titi" +FT CHAIN <1..>129 +FT /note="toto" +FT /evidence="titi" +FT CHAIN <1..55 +FT /note="toto" +FT /evidence="titi" +SQ SEQUENCE 246 AA; 28081 MW; CABA32314D86800D CRC64; + MTMDKSELVQ KAKLAEQAER YDDMAAAMKA VTEQGHELSN EERNLLSVAY KNVVGARRSS + WRVISSIEQK TERNEKKQQM GKEYREKIEA ELQDICNDVL QLLDKYLIPN ATQPESKVFY + LKMKGDYFRY LSEVASGDNK QTTVSNSQQA YQEAFEISKK EMQPTHPIRL GLALNFSVFY + YEILNSPEKA CSLAKTAFDE AIAELDTLNE ESYKDSTLIM QLLRDNLTLW TSENQGDEGD + AGEGEN +// diff --git a/tests/junit/databank/uniprot/single-up-test.dat b/tests/junit/databank/uniprot/single-up-test.dat new file mode 100644 index 0000000..8cd06fb --- /dev/null +++ b/tests/junit/databank/uniprot/single-up-test.dat @@ -0,0 +1,468 @@ +ID 11S1_ELAGV Reviewed; 12 AA. +AC C0HLM8; +DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot. +DT 26-FEB-2020, sequence version 1. +DT 10-FEB-2021, entry version 3. +DE RecName: Full=Globulin 1 {ECO:0000303|Ref.1}; +DE AltName: Full=11S globulin seed storage protein 1 {ECO:0000305}; +DE Contains: +DE RecName: Full=Globulin 1 basic chain {ECO:0000305}; +DE Flags: Fragment; +OS Elaeis guineensis var. tenera (Oil palm). +OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; +OC Spermatophyta; Magnoliopsida; Liliopsida; Arecaceae; Arecoideae; Cocoseae; +OC Elaeidinae; Elaeis. +OX NCBI_TaxID=51953; +RN [1] {ECO:0000305} +RP PROTEIN SEQUENCE. +RA Tapal A., Martin A., Kaul Tiku P.; +RT "Oil palm (Elaeis guineensis var. tenera) kernel globulin: Proteomic +RT characterization."; +RL Submitted (OCT-2019) to UniProtKB. +CC -!- FUNCTION: Seed storage protein. {ECO:0000250|UniProtKB:A0A222NNM9}. +CC -!- SUBUNIT: Hexamer; each subunit is composed of an acidic and a basic +CC chain derived from a single precursor and linked by a disulfide bond. +CC {ECO:0000250|UniProtKB:A0A222NNM9}. +CC -!- SIMILARITY: Belongs to the 11S seed storage protein (globulins) family. +CC {ECO:0000305}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR Proteomes; UP000504607; Genome assembly. +DR GO; GO:0045735; F:nutrient reservoir activity; IEA:UniProtKB-KW. +PE 1: Evidence at protein level; +KW Direct protein sequencing; Disulfide bond; Reference proteome; +KW Seed storage protein; Storage protein. +FT CHAIN 1..>12 +FT /note="Globulin 1 basic chain" +FT /evidence="ECO:0000305" +FT /id="PRO_0000448941" +FT DISULFID 7..? +FT /note="Interchain (between acidic and basic chains)" +FT /evidence="ECO:0000250|UniProtKB:A0A222NNM9" +FT NON_TER 12 +FT /evidence="ECO:0000305" +SQ SEQUENCE 12 AA; 1402 MW; 82741C1D1EBEAB41 CRC64; + GLEETYCSMK IK +// +ID 1433B_BOVIN Reviewed; 246 AA. +AC P68250; P29358; Q0VCL1; +DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot. +DT 23-JAN-2007, sequence version 2. +DT 23-FEB-2022, entry version 120. +DE RecName: Full=14-3-3 protein beta/alpha; +DE AltName: Full=Protein kinase C inhibitor protein 1; +DE Short=KCIP-1; +DE Contains: +DE RecName: Full=14-3-3 protein beta/alpha, N-terminally processed; +GN Name=YWHAB; +OS Bos taurus (Bovine). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; +OC Bovinae; Bos. +OX NCBI_TaxID=9913; +RN [1] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). +RC STRAIN=Hereford; TISSUE=Fetal pons; +RG NIH - Mammalian Gene Collection (MGC) project; +RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. +RN [2] +RP PROTEIN SEQUENCE OF 2-246. +RX PubMed=1671102; DOI=10.1016/0022-2836(91)90616-e; +RA Isobe T., Ichimura T., Sunaya T., Okuyama T., Takahashi N., Kuwano R., +RA Takahashi Y.; +RT "Distinct forms of the protein kinase-dependent activator of tyrosine and +RT tryptophan hydroxylases."; +RL J. Mol. Biol. 217:125-132(1991). +RN [3] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). +RA Jones J.M., Niikura T., Pinke R.M., Guo W., Molday L., Leykam J., +RA McConnell D.G.; +RT "Expression of 14-3-3 proteins in bovine retinal photoreceptors."; +RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. +RN [4] +RP FUNCTION. +RX PubMed=7931346; DOI=10.1046/j.1471-4159.1994.63051908.x; +RA Tanji M., Horwitz R., Rosenfeld G., Waymire J.C.; +RT "Activation of protein kinase C by purified bovine brain 14-3-3: comparison +RT with tyrosine hydroxylase activation."; +RL J. Neurochem. 63:1908-1916(1994). +CC -!- FUNCTION: Adapter protein implicated in the regulation of a large +CC spectrum of both general and specialized signaling pathways. Binds to a +CC large number of partners, usually by recognition of a phosphoserine or +CC phosphothreonine motif. Binding generally results in the modulation of +CC the activity of the binding partner. Negative regulator of +CC osteogenesis. Blocks the nuclear translocation of the phosphorylated +CC form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on +CC cyclin D1 expression resulting in blockage of neuronal apoptosis +CC elicited by SRPK2. Negative regulator of signaling cascades that +CC mediate activation of MAP kinases via AKAP13. +CC {ECO:0000250|UniProtKB:P31946, ECO:0000269|PubMed:7931346}. +CC -!- SUBUNIT: Homodimer (By similarity). Interacts with SAMSN1 and PRKCE (By +CC similarity). Interacts with AKAP13. Interacts with SSH1 and +CC TORC2/CRTC2. Interacts with ABL1; the interaction results in +CC cytoplasmic location of ABL1 and inhibition of cABL-mediated apoptosis. +CC Interacts with ROR2 (dimer); the interaction results in phosphorylation +CC of YWHAB on tyrosine residues. Interacts with GAB2. Interacts with YAP1 +CC (phosphorylated form). Interacts with the phosphorylated (by AKT1) form +CC of SRPK2. Interacts with PKA-phosphorylated AANAT. Interacts with +CC MYO1C. Interacts with SIRT2 (By similarity). Interacts with the 'Thr- +CC 369' phosphorylated form of DAPK2 (By similarity). Interacts with +CC PI4KB, TBC1D22A and TBC1D22B. Interacts with the 'Ser-1134' and 'Ser- +CC 1161' phosphorylated form of SOS1 (By similarity). Interacts (via +CC phosphorylated form) with YWHAB; this interaction occurs in a protein +CC kinase AKT1-dependent manner (By similarity). Interacts with SLITRK1. +CC Interacts with SYNPO2 (phosphorylated form); YWHAB competes with ACTN2 +CC for interaction with SYNPO2 (By similarity). Interacts with RIPOR2 (via +CC phosphorylated form); this interaction occurs in a chemokine-dependent +CC manner and does not compete for binding of RIPOR2 with RHOA nor blocks +CC inhibition of RIPOR2-mediated RHOA activity (By similarity). Interacts +CC with MARK2 and MARK3 (By similarity). Interacts with TESK1; the +CC interaction is dependent on the phosphorylation of TESK1 'Ser-439' and +CC inhibits TESK1 kinase activity (By similarity). Interacts with MEFV (By +CC similarity). {ECO:0000250|UniProtKB:P31946, +CC ECO:0000250|UniProtKB:Q9CQV8}. +CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31946}. +CC Melanosome {ECO:0000250|UniProtKB:P31946}. +CC -!- ALTERNATIVE PRODUCTS: +CC Event=Alternative initiation; Named isoforms=2; +CC Comment=It is uncertain whether isoform Short is produced by +CC alternative initiation or another biological event.; +CC Name=Long; +CC IsoId=P68250-1; Sequence=Displayed; +CC Name=Short; +CC IsoId=P68250-2; Sequence=VSP_018631; +CC -!- PTM: The alpha, brain-specific form differs from the beta form in being +CC phosphorylated. Phosphorylated on Ser-60 by protein kinase C delta type +CC catalytic subunit in a sphingosine-dependent fashion. {ECO:0000250}. +CC -!- SIMILARITY: Belongs to the 14-3-3 family. {ECO:0000305}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; BC120112; AAI20113.1; -; mRNA. +DR EMBL; AF043736; AAC02090.1; -; mRNA. +DR PIR; S13467; S13467. +DR RefSeq; NP_777219.2; NM_174794.2. +DR SMR; P68250; -. +DR STRING; 9913.ENSBTAP00000022411; -. +DR iPTMnet; P68250; -. +DR PaxDb; P68250; -. +DR PeptideAtlas; P68250; -. +DR PRIDE; P68250; -. +DR GeneID; 286863; -. +DR KEGG; bta:286863; -. +DR CTD; 7529; -. +DR eggNOG; KOG0841; Eukaryota. +DR HOGENOM; CLU_058290_1_0_1; -. +DR InParanoid; P68250; -. +DR OrthoDB; 1176818at2759; -. +DR TreeFam; TF102003; -. +DR Proteomes; UP000009136; Unplaced. +DR GO; GO:0005737; C:cytoplasm; ISS:AgBase. +DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. +DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:AgBase. +DR GO; GO:0019904; F:protein domain specific binding; ISS:AgBase. +DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB. +DR GO; GO:0034613; P:cellular protein localization; IBA:GO_Central. +DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB. +DR GO; GO:0006605; P:protein targeting; ISS:AgBase. +DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. +DR Gene3D; 1.20.190.20; -; 1. +DR InterPro; IPR000308; 14-3-3. +DR InterPro; IPR023409; 14-3-3_CS. +DR InterPro; IPR036815; 14-3-3_dom_sf. +DR InterPro; IPR023410; 14-3-3_domain. +DR PANTHER; PTHR18860; PTHR18860; 1. +DR Pfam; PF00244; 14-3-3; 1. +DR PIRSF; PIRSF000868; 14-3-3; 1. +DR PRINTS; PR00305; 1433ZETA. +DR SMART; SM00101; 14_3_3; 1. +DR SUPFAM; SSF48445; SSF48445; 1. +DR PROSITE; PS00796; 1433_1; 1. +DR PROSITE; PS00797; 1433_2; 1. +PE 1: Evidence at protein level; +KW Acetylation; Alternative initiation; Cytoplasm; Direct protein sequencing; +KW Isopeptide bond; Nitration; Phosphoprotein; Reference proteome; +KW Ubl conjugation. +FT MOD_RES P68251-2:1 +FT /note="N-acetylmethionine" +FT /evidence="ECO:0000269|PubMed:1317796" +FT CHAIN 1..246 +FT /note="14-3-3 protein beta/alpha" +FT /id="PRO_0000367899" +FT INIT_MET 1 +FT /note="Removed; alternate" +FT /evidence="ECO:0000250|UniProtKB:P31946, +FT ECO:0000269|PubMed:1671102" +FT CHAIN 2..246 +FT /note="14-3-3 protein beta/alpha, N-terminally processed" +FT /id="PRO_0000000001" +FT SITE 58 +FT /note="Interaction with phosphoserine on interacting +FT protein" +FT /evidence="ECO:0000250" +FT SITE 129 +FT /note="Interaction with phosphoserine on interacting +FT protein" +FT /evidence="ECO:0000250" +FT MOD_RES 1 +FT /note="N-acetylmethionine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 2 +FT /note="N-acetylthreonine; in 14-3-3 protein beta/alpha, N- +FT terminally processed" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 2 +FT /note="Phosphothreonine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 5 +FT /note="N6-acetyllysine" +FT /evidence="ECO:0000250|UniProtKB:P27348" +FT MOD_RES 51 +FT /note="N6-acetyllysine; alternate" +FT /evidence="ECO:0000250|UniProtKB:P27348" +FT MOD_RES 60 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:Q9CQV8" +FT MOD_RES 70 +FT /note="N6-acetyllysine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 84 +FT /note="3'-nitrotyrosine" +FT /evidence="ECO:0000250|UniProtKB:Q9CQV8" +FT MOD_RES 106 +FT /note="3'-nitrotyrosine" +FT /evidence="ECO:0000250|UniProtKB:Q9CQV8" +FT MOD_RES 117 +FT /note="N6-acetyllysine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 186 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:P68251" +FT MOD_RES 232 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT CROSSLNK 51 +FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with +FT G-Cter in SUMO2); alternate" +FT /evidence="ECO:0000250|UniProtKB:P27348" +FT VAR_SEQ 1..2 +FT /note="Missing (in isoform Short)" +FT /evidence="ECO:0000303|Ref.3" +FT /id="VSP_018631" +FT CONFLICT 101 +FT /note="Q -> E (in Ref. 1; AAI20113)" +FT /evidence="ECO:0000305" +FT MOD_RES P68250-2:1 +FT /note="N-acetylmethionine" +FT /evidence="ECO:0000250" +SQ SEQUENCE 246 AA; 28081 MW; CABA32314D86800D CRC64; + MTMDKSELVQ KAKLAEQAER YDDMAAAMKA VTEQGHELSN EERNLLSVAY KNVVGARRSS + WRVISSIEQK TERNEKKQQM GKEYREKIEA ELQDICNDVL QLLDKYLIPN ATQPESKVFY + LKMKGDYFRY LSEVASGDNK QTTVSNSQQA YQEAFEISKK EMQPTHPIRL GLALNFSVFY + YEILNSPEKA CSLAKTAFDE AIAELDTLNE ESYKDSTLIM QLLRDNLTLW TSENQGDEGD + AGEGEN +// +ID 1433B_SHEEP Reviewed; 193 AA. +AC P68251; P29358; +DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot. +DT 23-JAN-2007, sequence version 2. +DT 02-JUN-2021, entry version 97. +DE RecName: Full=14-3-3 protein beta/alpha; +DE AltName: Full=Protein kinase C inhibitor protein 1; +DE Short=KCIP-1; +DE Contains: +DE RecName: Full=14-3-3 protein beta/alpha, N-terminally processed; +DE Flags: Fragments; +GN Name=YWHAB; +OS Ovis aries (Sheep). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; +OC Caprinae; Ovis. +OX NCBI_TaxID=9940; +RN [1] +RP PROTEIN SEQUENCE (ISOFORM SHORT), AND ACETYLATION AT MET-1 (ISOFORM SHORT). +RC TISSUE=Brain; +RX PubMed=1317796; DOI=10.1111/j.1432-1033.1992.tb16946.x; +RA Toker A., Sellers L.A., Amess B., Patel Y., Harris A., Aitken A.; +RT "Multiple isoforms of a protein kinase C inhibitor (KCIP-1/14-3-3) from +RT sheep brain. Amino acid sequence of phosphorylated forms."; +RL Eur. J. Biochem. 206:453-461(1992). +RN [2] +RP PROTEIN SEQUENCE OF 3-24 (ISOFORM LONG). +RC TISSUE=Brain; +RX PubMed=2143472; DOI=10.1111/j.1432-1033.1990.tb19138.x; +RA Toker A., Ellis C.A., Sellers L.A., Aitken A.; +RT "Protein kinase C inhibitor proteins. Purification from sheep brain and +RT sequence similarity to lipocortins and 14-3-3 protein."; +RL Eur. J. Biochem. 191:421-429(1990). +RN [3] +RP PHOSPHORYLATION AT SER-149, AND IDENTIFICATION BY MASS SPECTROMETRY. +RX PubMed=7890696; DOI=10.1074/jbc.270.11.5706; +RA Aitken A., Howell S., Jones D., Madrazo J., Patel Y.; +RT "14-3-3 alpha and delta are the phosphorylated forms of raf-activating 14- +RT 3-3 beta and zeta. In vivo stoichiometric phosphorylation in brain at a +RT Ser-Pro-Glu-Lys motif."; +RL J. Biol. Chem. 270:5706-5709(1995). +RN [4] +RP ACETYLATION AT THR-2, AND IDENTIFICATION BY MASS SPECTROMETRY. +RA Aitken A., Patel Y., Martin H., Jones D., Robinson K., Madrazo J., +RA Howell S.; +RT "Electrospray mass spectroscopy analysis with online trapping of +RT posttranslationally modified mammalian and avian brain 14-3-3 isoforms."; +RL J. Protein Chem. 13:463-465(1994). +RN [5] +RP INTERACTION WITH AANAT. +RX PubMed=11427721; DOI=10.1073/pnas.141118798; +RA Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H., +RA Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T., +RA Beauverger P., Ferry G., Boutin J.A., Klein D.C.; +RT "Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3- +RT binding switch in melatonin synthesis."; +RL Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001). +CC -!- FUNCTION: Adapter protein implicated in the regulation of a large +CC spectrum of both general and specialized signaling pathways. Binds to a +CC large number of partners, usually by recognition of a phosphoserine or +CC phosphothreonine motif. Binding generally results in the modulation of +CC the activity of the binding partner. Negative regulator of +CC osteogenesis. Blocks the nuclear translocation of the phosphorylated +CC form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on +CC cyclin D1 expression resulting in blockage of neuronal apoptosis +CC elicited by SRPK2. Negative regulator of signaling cascades that +CC mediate activation of MAP kinases via AKAP13. +CC {ECO:0000250|UniProtKB:P31946}. +CC -!- SUBUNIT: Homodimer (By similarity). Interacts with SAMSN1 and PRKCE (By +CC similarity). Interacts with AKAP13. Interacts with SSH1 and +CC TORC2/CRTC2. Interacts with ABL1; the interaction results in +CC cytoplasmic location of ABL1 and inhibition of cABL-mediated apoptosis. +CC Interacts with ROR2 (dimer); the interaction results in phosphorylation +CC of YWHAB on tyrosine residues. Interacts with GAB2. Interacts with YAP1 +CC (phosphorylated form). Interacts with the phosphorylated (by AKT1) form +CC of SRPK2 (By similarity). Interacts with PKA-phosphorylated AANAT +CC (PubMed:11427721). Interacts with MYO1C. Interacts with SIRT2 (By +CC similarity). Interacts with the 'Thr-369' phosphorylated form of DAPK2 +CC (By similarity). Interacts with PI4KB, TBC1D22A and TBC1D22B. Interacts +CC with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By +CC similarity). Interacts (via phosphorylated form) with YWHAB; this +CC interaction occurs in a protein kinase AKT1-dependent manner (By +CC similarity). Interacts with SLITRK1. Interacts with SYNPO2 +CC (phosphorylated form); YWHAB competes with ACTN2 for interaction with +CC SYNPO2 (By similarity). Interacts with RIPOR2 (via phosphorylated +CC form); this interaction occurs in a chemokine-dependent manner and does +CC not compete for binding of RIPOR2 with RHOA nor blocks inhibition of +CC RIPOR2-mediated RHOA activity (By similarity). Interacts with MARK2 and +CC MARK3 (By similarity). Interacts with TESK1; the interaction is +CC dependent on the phosphorylation of TESK1 'Ser-430' and inhibits TESK1 +CC kinase activity (By similarity). Interacts with MEFV (By similarity). +CC {ECO:0000250|UniProtKB:P31946, ECO:0000250|UniProtKB:Q9CQV8, +CC ECO:0000269|PubMed:11427721}. +CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31946}. +CC Melanosome {ECO:0000250|UniProtKB:P31946}. +CC -!- ALTERNATIVE PRODUCTS: +CC Event=Alternative initiation; Named isoforms=2; +CC Comment=It is uncertain whether isoform Short is produced by +CC alternative initiation or another biological event.; +CC Name=Long; +CC IsoId=P68251-1; Sequence=Displayed; +CC Name=Short; +CC IsoId=P68251-2; Sequence=VSP_018636; +CC -!- PTM: Form alpha differs from form beta in being phosphorylated. +CC Phosphorylated on Ser-60 by protein kinase C delta type catalytic +CC subunit in a sphingosine-dependent fashion (By similarity). +CC {ECO:0000250}. +CC -!- SIMILARITY: Belongs to the 14-3-3 family. {ECO:0000305}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR SMR; P68251; -. +DR iPTMnet; P68251; -. +DR OMA; KGCQLAR; -. +DR Proteomes; UP000002356; Unplaced. +DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. +DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB. +DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB. +DR Gene3D; 1.20.190.20; -; 2. +DR InterPro; IPR000308; 14-3-3. +DR InterPro; IPR023409; 14-3-3_CS. +DR InterPro; IPR036815; 14-3-3_dom_sf. +DR InterPro; IPR023410; 14-3-3_domain. +DR PANTHER; PTHR18860; PTHR18860; 2. +DR Pfam; PF00244; 14-3-3; 2. +DR SMART; SM00101; 14_3_3; 1. +DR SUPFAM; SSF48445; SSF48445; 1. +DR PROSITE; PS00796; 1433_1; 1. +DR PROSITE; PS00797; 1433_2; 1. +PE 1: Evidence at protein level; +KW Acetylation; Alternative initiation; Cytoplasm; Direct protein sequencing; +KW Isopeptide bond; Nitration; Phosphoprotein; Reference proteome; +KW Ubl conjugation. +FT CHAIN 1..193 +FT /note="14-3-3 protein beta/alpha" +FT /id="PRO_0000367905" +FT INIT_MET 1 +FT /note="Removed; alternate" +FT /evidence="ECO:0000250|UniProtKB:P68250" +FT CHAIN 2..193 +FT /note="14-3-3 protein beta/alpha, N-terminally processed" +FT /id="PRO_0000000009" +FT SITE 58 +FT /note="Interaction with phosphoserine on interacting +FT protein" +FT /evidence="ECO:0000250" +FT SITE 92 +FT /note="Interaction with phosphoserine on interacting +FT protein" +FT /evidence="ECO:0000250" +FT MOD_RES 1 +FT /note="N-acetylmethionine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 2 +FT /note="N-acetylthreonine; in 14-3-3 protein beta/alpha, N- +FT terminally processed" +FT /evidence="ECO:0000269|Ref.4" +FT MOD_RES 2 +FT /note="Phosphothreonine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 5 +FT /note="N6-acetyllysine" +FT /evidence="ECO:0000250|UniProtKB:P27348" +FT MOD_RES 51 +FT /note="N6-acetyllysine; alternate" +FT /evidence="ECO:0000250|UniProtKB:P27348" +FT MOD_RES 60 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:Q9CQV8" +FT MOD_RES 70 +FT /note="N6-acetyllysine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT MOD_RES 84 +FT /note="3'-nitrotyrosine" +FT /evidence="ECO:0000250|UniProtKB:Q9CQV8" +FT MOD_RES 149 +FT /note="Phosphoserine" +FT /evidence="ECO:0000269|PubMed:7890696" +FT MOD_RES 183 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:P31946" +FT CROSSLNK 51 +FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with +FT G-Cter in SUMO2); alternate" +FT /evidence="ECO:0000250|UniProtKB:P27348" +FT VAR_SEQ 1..2 +FT /note="Missing (in isoform Short)" +FT /evidence="ECO:0000305" +FT /id="VSP_018636" +FT NON_CONS 84..85 +FT /evidence="ECO:0000305" +FT NON_CONS 150..151 +FT /evidence="ECO:0000305" +FT NON_TER 193 +SQ SEQUENCE 193 AA; 22054 MW; 923914FE5226E608 CRC64; + MTMDKSELVQ KAKLAEQAER YDDMAAAMKA VTEQGHELSN EERNLLSVAY KNVVGARRSS + WRVISSIEQK TERNEKKQQM GKEYKMKGDY FRYLSEVASG DNKQTTVSNS QQAYQEAFEI + SKKEMQPTHP IRLGLALNFS VFYYEILNSP EAIAELDTLN EESYKDSTLI MQLLRDNLTL + WTSENQGDEG DAG +// diff --git a/tests/junit/databank/uniprot/uniprot_new.dat b/tests/junit/databank/uniprot/uniprot_new.dat new file mode 100644 index 0000000..63174a8 --- /dev/null +++ b/tests/junit/databank/uniprot/uniprot_new.dat @@ -0,0 +1,2422 @@ +ID KKCC1_RAT Reviewed; 505 AA. +AC P97756; Q64572; Q794E3; +DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot. +DT 01-MAY-1997, sequence version 1. +DT 23-FEB-2022, entry version 149. +DE RecName: Full=Calcium/calmodulin-dependent protein kinase kinase 1; +DE Short=CaM-KK 1; +DE Short=CaM-kinase kinase 1; +DE Short=CaMKK 1; +DE EC=2.7.11.17; +DE AltName: Full=CaM-kinase IV kinase; +DE AltName: Full=Calcium/calmodulin-dependent protein kinase kinase alpha; +DE Short=CaM-KK alpha; +DE Short=CaM-kinase kinase alpha; +DE Short=CaMKK alpha; +GN Name=Camkk1; +OS Rattus norvegicus (Rat). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; +OC Murinae; Rattus. +OX NCBI_TaxID=10116; +RN [1] +RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-230 AND 291-310, +RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH CALMODULIN, AND TISSUE +RP SPECIFICITY. +RC TISSUE=Brain; +RX PubMed=7642608; DOI=10.1074/jbc.270.33.19320; +RA Tokumitsu H., Enslen H., Soderling T.R.; +RT "Characterization of a Ca2+/calmodulin-dependent protein kinase cascade. +RT Molecular cloning and expression of calcium/calmodulin-dependent protein +RT kinase kinase."; +RL J. Biol. Chem. 270:19320-19324(1995). +RN [2] +RP NUCLEOTIDE SEQUENCE [MRNA]. +RC TISSUE=Brain; +RX PubMed=8827455; DOI=10.1093/oxfordjournals.jbchem.a021365; +RA Okuno S., Kitani T., Fujisawa H.; +RT "Evidence for the existence of Ca2+/calmodulin-dependent protein kinase IV +RT kinase isoforms in rat brain."; +RL J. Biochem. 119:1176-1181(1996). +RN [3] +RP PROTEIN SEQUENCE OF 4-13; 20-38; 50-60; 137-148; 196-210; 275-288; 291-311; +RP 333-340; 351-360; 365-382; 389-397; 405-408; 440-444; 458-468 AND 473-478, +RP FUNCTION IN PHOSPHORYLATION OF CAMK1 AND CAMK4, AND AUTOPHOSPHORYLATION. +RX PubMed=8631893; DOI=10.1074/jbc.271.18.10806; +RA Edelman A.M., Mitchelhill K.I., Selbert M.A., Anderson K.A., Hook S.S., +RA Stapleton D., Goldstein E.G., Means A.R., Kemp B.E.; +RT "Multiple Ca(2+)-calmodulin-dependent protein kinase kinases from rat +RT brain. Purification, regulation by Ca(2+)-calmodulin, and partial amino +RT acid sequence."; +RL J. Biol. Chem. 271:10806-10810(1996). +RN [4] +RP SUBCELLULAR LOCATION. +RX PubMed=8929978; DOI=10.1016/0304-3940(96)12317-x; +RA Nakamura Y., Okuno S., Kitani T., Otake K., Sato F., Fujisawa H.; +RT "Distribution of Ca2+/calmodulin-dependent protein kinase kinase alpha in +RT the rat central nervous system: an immunohistochemical study."; +RL Neurosci. Lett. 204:61-64(1996). +RN [5] +RP CHARACTERIZATION, AND REGION. +RX PubMed=9335539; DOI=10.1021/bi971348i; +RA Tokumitsu H., Wayman G.A., Muramatsu M.-A., Soderling T.R.; +RT "Calcium/calmodulin-dependent protein kinase kinase: identification of +RT regulatory domains."; +RL Biochemistry 36:12823-12827(1997). +RN [6] +RP PHOSPHORYLATION AT THR-108 AND SER-458, MUTAGENESIS OF THR-108 AND SER-458, +RP AND PHOSPHORYLATION BY PRCAKA. +RX PubMed=9195898; DOI=10.1074/jbc.272.26.16073; +RA Wayman G.A., Tokumitsu H., Soderling T.R.; +RT "Inhibitory cross-talk by cAMP kinase on the calmodulin-dependent protein +RT kinase cascade."; +RL J. Biol. Chem. 272:16073-16076(1997). +RN [7] +RP FUNCTION IN PHOSPHORYLATION OF AKT1. +RX PubMed=9859994; DOI=10.1038/25147; +RA Yano S., Tokumitsu H., Soderling T.R.; +RT "Calcium promotes cell survival through CaM-K kinase activation of the +RT protein-kinase-B pathway."; +RL Nature 396:584-587(1998). +RN [8] +RP PHOSPHORYLATION AT SER-74 AND THR-108, MUTAGENESIS OF SER-74 AND THR-108, +RP PHOSPHORYLATION BY PRCAKA, AND TISSUE SPECIFICITY. +RX PubMed=10187789; DOI=10.1074/jbc.274.15.10086; +RA Matsushita M., Nairn A.C.; +RT "Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by +RT cAMP-dependent protein kinase."; +RL J. Biol. Chem. 274:10086-10093(1999). +RN [9] +RP MUTAGENESIS OF ARG-172 AND ARG-177, DOMAIN RP, AND INTERACTION WITH CAMK4. +RX PubMed=10336483; DOI=10.1074/jbc.274.22.15803; +RA Tokumitsu H., Takahashi N., Eto K., Yano S., Soderling T.R., +RA Muramatsu M.-A.; +RT "Substrate recognition by Ca2+/Calmodulin-dependent protein kinase kinase. +RT Role of the arg-pro-rich insert domain."; +RL J. Biol. Chem. 274:15803-15810(1999). +RN [10] +RP SUBCELLULAR LOCATION. +RX PubMed=10651863; DOI=10.1046/j.1460-9568.2000.00883.x; +RA Sakagami H., Umemiya M., Saito S., Kondo H.; +RT "Distinct immunohistochemical localization of two isoforms of +RT Ca2+/calmodulin-dependent protein kinase kinases in the adult rat brain."; +RL Eur. J. Neurosci. 12:89-99(2000). +RN [11] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-475, AND +RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RX PubMed=22673903; DOI=10.1038/ncomms1871; +RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., +RA Olsen J.V.; +RT "Quantitative maps of protein phosphorylation sites across 14 different rat +RT organs and tissues."; +RL Nat. Commun. 3:876-876(2012). +RN [12] +RP STRUCTURE BY NMR OF 438-463 IN COMPLEX WITH CA(2+)/CALMODULIN, MUTAGENESIS +RP OF PHE-459 AND PHE-463, AND REGION. +RX PubMed=10467092; DOI=10.1038/12271; +RA Osawa M., Tokumitsu H., Swindells M.B., Kurihara H., Orita M., +RA Shibanuma T., Furuya T., Ikura M.; +RT "A novel target recognition revealed by calmodulin in complex with Ca2+- +RT calmodulin-dependent kinase kinase."; +RL Nat. Struct. Biol. 6:819-824(1999). +CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that belongs to a +CC proposed calcium-triggered signaling cascade involved in a number of +CC cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. +CC Involved in regulating cell apoptosis. Promotes cell survival by +CC phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2- +CC antagonist of cell death. {ECO:0000269|PubMed:7642608, +CC ECO:0000269|PubMed:8631893, ECO:0000269|PubMed:9859994}. +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- +CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- +CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, +CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- +CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, +CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; +CC EC=2.7.11.17; +CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of +CC calmodulin may relieve intrasteric autoinhibition. Partially inhibited +CC upon phosphorylation by PRCAKA/PKA. May be regulated through +CC phosphorylation by CAMK1 and CAMK4. {ECO:0000269|PubMed:7642608}. +CC -!- SUBUNIT: Interacts with CAMK4 and calmodulin. +CC {ECO:0000269|PubMed:10336483, ECO:0000269|PubMed:10467092, +CC ECO:0000269|PubMed:7642608}. +CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. +CC -!- TISSUE SPECIFICITY: Mostly expressed in the brain with higher levels in +CC cortex and hippocampus. Lower expression levels were detected in +CC striatum, nucleus accumbens and cerebellum (at protein level). Abundant +CC in forebrain, weaker in cerebellum and also detected in thymus and +CC spleen. {ECO:0000269|PubMed:10187789, ECO:0000269|PubMed:7642608}. +CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding +CC region and may be involved in intrasteric autoinhibition. +CC {ECO:0000269|PubMed:10336483}. +CC -!- DOMAIN: The RP domain (arginine/proline-rich) is involved in the +CC recognition of CAMKI and CAMK4 as substrates. +CC {ECO:0000269|PubMed:10336483}. +CC -!- PTM: Appears to be autophosphorylated. Phosphorylated at multiple sites +CC by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to +CC Ca(2+)/calmodulin. May be phosphorylated by CAMK1 and CAMK4. +CC {ECO:0000269|PubMed:10187789, ECO:0000269|PubMed:9195898}. +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein +CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; L42810; AAC42070.1; -; mRNA. +DR EMBL; AB023658; BAA75246.1; -; mRNA. +DR EMBL; S83194; AAB46910.1; -; mRNA. +DR PIR; A57156; A57156. +DR RefSeq; NP_113850.1; NM_031662.1. +DR PDB; 1CKK; NMR; -; B=438-463. +DR PDBsum; 1CKK; -. +DR BMRB; P97756; -. +DR SMR; P97756; -. +DR BioGRID; 248789; 3. +DR IntAct; P97756; 4. +DR MINT; P97756; -. +DR STRING; 10116.ENSRNOP00000025009; -. +DR iPTMnet; P97756; -. +DR PhosphoSitePlus; P97756; -. +DR PaxDb; P97756; -. +DR GeneID; 60341; -. +DR KEGG; rno:60341; -. +DR CTD; 84254; -. +DR RGD; 62023; Camkk1. +DR eggNOG; KOG0585; Eukaryota. +DR InParanoid; P97756; -. +DR OrthoDB; 1044255at2759; -. +DR PhylomeDB; P97756; -. +DR BRENDA; 2.7.11.17; 5301. +DR Reactome; R-RNO-111932; CaMK IV-mediated phosphorylation of CREB. +DR Reactome; R-RNO-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde. +DR Reactome; R-RNO-9619229; Activation of RAC1 downstream of NMDARs. +DR EvolutionaryTrace; P97756; -. +DR PRO; PR:P97756; -. +DR Proteomes; UP000002494; Unplaced. +DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. +DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. +DR GO; GO:0005516; F:calmodulin binding; IDA:RGD. +DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:RGD. +DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. +DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:RHEA. +DR GO; GO:0032147; P:activation of protein kinase activity; IDA:RGD. +DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. +DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:RGD. +DR GO; GO:0006468; P:protein phosphorylation; TAS:RGD. +DR IDEAL; IID50177; -. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR017441; Protein_kinase_ATP_BS. +DR InterPro; IPR008271; Ser/Thr_kinase_AS. +DR Pfam; PF00069; Pkinase; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. +PE 1: Evidence at protein level; +KW 3D-structure; ATP-binding; Calmodulin-binding; Cytoplasm; +KW Direct protein sequencing; Kinase; Methylation; Nucleotide-binding; +KW Nucleus; Phosphoprotein; Reference proteome; +KW Serine/threonine-protein kinase; Transferase. +FT CHAIN 1..505 +FT /note="Calcium/calmodulin-dependent protein kinase kinase +FT 1" +FT /id="PRO_0000086143" +FT DOMAIN 128..409 +FT /note="Protein kinase" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT NP_BIND 134..142 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT REGION 27..66 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 167..189 +FT /note="RP domain" +FT /evidence="ECO:0000269|PubMed:10336483" +FT REGION 435..440 +FT /note="Autoinhibitory domain" +FT /evidence="ECO:0000269|PubMed:10336483, +FT ECO:0000269|PubMed:9335539" +FT REGION 438..463 +FT /note="Calmodulin-binding" +FT /evidence="ECO:0000269|PubMed:10467092, +FT ECO:0000269|PubMed:9335539" +FT REGION 460..505 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT ACT_SITE 275 +FT /note="Proton acceptor" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, +FT ECO:0000255|PROSITE-ProRule:PRU10027" +FT BINDING 157 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT MOD_RES 67 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:Q8N5S9" +FT MOD_RES 74 +FT /note="Phosphoserine" +FT /evidence="ECO:0000269|PubMed:10187789" +FT MOD_RES 78 +FT /note="Asymmetric dimethylarginine" +FT /evidence="ECO:0000250|UniProtKB:Q8VBY2" +FT MOD_RES 100 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:Q8VBY2" +FT MOD_RES 108 +FT /note="Phosphothreonine" +FT /evidence="ECO:0000269|PubMed:10187789, +FT ECO:0000269|PubMed:9195898" +FT MOD_RES 458 +FT /note="Phosphoserine" +FT /evidence="ECO:0000269|PubMed:9195898, +FT ECO:0007744|PubMed:22673903" +FT MOD_RES 475 +FT /note="Phosphoserine" +FT /evidence="ECO:0007744|PubMed:22673903" +FT MOD_RES 492 +FT /note="Phosphoserine" +FT /evidence="ECO:0000250|UniProtKB:Q8N5S9" +FT MUTAGEN 74 +FT /note="S->A: Decrease in phosphorylation by PKA." +FT /evidence="ECO:0000269|PubMed:10187789" +FT MUTAGEN 108 +FT /note="T->A: Decrease in phosphorylation and partial +FT inhibition by PKA. Almost loss of inhibition by PKA; when +FT associated with A-458." +FT /evidence="ECO:0000269|PubMed:10187789, +FT ECO:0000269|PubMed:9195898" +FT MUTAGEN 172 +FT /note="R->E: Loss of substrate recognition and interaction +FT with CAMK4." +FT /evidence="ECO:0000269|PubMed:10336483" +FT MUTAGEN 177 +FT /note="R->E: Loss of substrate recognition and interaction +FT with CAMK4." +FT /evidence="ECO:0000269|PubMed:10336483" +FT MUTAGEN 458 +FT /note="S->A: Decrease in phosphorylation and partial +FT inhibition by PKA. Almost loss of inhibition by PKA; when +FT associated with A-108." +FT /evidence="ECO:0000269|PubMed:9195898" +FT MUTAGEN 459 +FT /note="F->D: Loss of binding to Ca(2+)/calmodulin." +FT /evidence="ECO:0000269|PubMed:10467092" +FT MUTAGEN 463 +FT /note="F->D: Loss of binding to Ca(2+)/calmodulin." +FT /evidence="ECO:0000269|PubMed:10467092" +FT CONFLICT 45 +FT /note="P -> S (in Ref. 1; AAC42070)" +FT /evidence="ECO:0000305" +FT CONFLICT 81 +FT /note="G -> E (in Ref. 1; AAC42070)" +FT /evidence="ECO:0000305" +FT HELIX 444..453 +FT /evidence="ECO:0007829|PDB:1CKK" +FT STRAND 455..457 +FT /evidence="ECO:0007829|PDB:1CKK" +SQ SEQUENCE 505 AA; 55908 MW; 6B268780AC9B67E1 CRC64; + MERSPAVCCQ DPRAELVERV AAISVAHLEE AEEGPEPASN GVDPPPRARA ASVIPGSASR + PTPVRPSLSA RKFSLQERPA GSCLEAQVGP YSTGPASHMS PRAWRRPTIE SHHVAISDTE + DCVQLNQYKL QSEIGKGAYG VVRLAYNERE DRHYAMKVLS KKKLLKQYGF PRRPPPRGSQ + APQGGPAKQL LPLERVYQEI AILKKLDHVN VVKLIEVLDD PAEDNLYLVF DLLRKGPVME + VPCDKPFPEE QARLYLRDII LGLEYLHCQK IVHRDIKPSN LLLGDDGHVK IADFGVSNQF + EGNDAQLSST AGTPAFMAPE AISDTGQSFS GKALDVWATG VTLYCFVYGK CPFIDEYILA + LHRKIKNEAV VFPEEPEVSE ELKDLILKML DKNPETRIGV SDIKLHPWVT KHGEEPLPSE + EEHCSVVEVT EEEVKNSVKL IPSWTTVILV KSMLRKRSFG NPFEPQARRE ERSMSAPGNL + LLKEGCGEGG KSPELPGVQE DEAAS +// +ID M4K2_HUMAN Reviewed; 820 AA. +AC Q12851; Q86VU3; +DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. +DT 25-NOV-2008, sequence version 2. +DT 23-FEB-2022, entry version 198. +DE RecName: Full=Mitogen-activated protein kinase kinase kinase kinase 2; +DE EC=2.7.11.1; +DE AltName: Full=B lymphocyte serine/threonine-protein kinase; +DE AltName: Full=Germinal center kinase; +DE Short=GC kinase; +DE AltName: Full=MAPK/ERK kinase kinase kinase 2; +DE Short=MEK kinase kinase 2; +DE Short=MEKKK 2; +DE AltName: Full=Rab8-interacting protein; +GN Name=MAP4K2; Synonyms=GCK, RAB8IP; +OS Homo sapiens (Human). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; +OC Homo. +OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAA20968.1}; +RN [1] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RX PubMed=16554811; DOI=10.1038/nature04632; +RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., +RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., +RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., +RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., +RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., +RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; +RT "Human chromosome 11 DNA sequence and analysis including novel gene +RT identification."; +RL Nature 440:497-500(2006). +RN [2] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., +RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., +RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., +RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., +RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., +RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., +RA Hunkapiller M.W., Myers E.W., Venter J.C.; +RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. +RN [3] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). +RC TISSUE=Uterus; +RX PubMed=15489334; DOI=10.1101/gr.2596504; +RG The MGC Project Team; +RT "The status, quality, and expansion of the NIH full-length cDNA project: +RT the Mammalian Gene Collection (MGC)."; +RL Genome Res. 14:2121-2127(2004). +RN [4] {ECO:0000305} +RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-820 (ISOFORM 1), FUNCTION, DOMAIN, AND +RP TISSUE SPECIFICITY. +RC TISSUE=Tonsil; +RX PubMed=7515885; +RA Katz P., Whalen G., Kehrl J.H.; +RT "Differential expression of a novel protein kinase in human B lymphocytes. +RT Preferential localization in the germinal center."; +RL J. Biol. Chem. 269:16802-16809(1994). +RN [5] +RP FUNCTION, AND ACTIVITY REGULATION. +RX PubMed=7477268; DOI=10.1038/377750a0; +RA Pombo C.M., Kehrl J.H., Sanchez I., Katz P., Avruch J., Zon L.I., +RA Woodgett J.R., Force T., Kyriakis J.M.; +RT "Activation of the SAPK pathway by the human STE20 homologue germinal +RT centre kinase."; +RL Nature 377:750-754(1995). +RN [6] +RP FUNCTION, AUTOPHOSPHORYLATION, AND INTERACTION WITH MAP3K1/MEKK1 AND TRAF2. +RX PubMed=9712898; DOI=10.1074/jbc.273.35.22681; +RA Yuasa T., Ohno S., Kehrl J.H., Kyriakis J.M.; +RT "Tumor necrosis factor signaling to stress-activated protein kinase +RT (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase +RT couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and +RT SAPK while receptor interacting protein associates with a mitogen-activated +RT protein kinase kinase kinase upstream of MKK6 and p38."; +RL J. Biol. Chem. 273:22681-22692(1998). +RN [7] {ECO:0000305} +RP FUNCTION, AND INTERACTION WITH TRAF2 AND MAP3K1. +RX PubMed=11784851; DOI=10.1128/mcb.22.3.737-749.2002; +RA Chadee D.N., Yuasa T., Kyriakis J.M.; +RT "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 +RT by the Ste20p homologue GCK and the adapter protein TRAF2."; +RL Mol. Cell. Biol. 22:737-749(2002). +RN [8] +RP ACTIVITY REGULATION, FUNCTION, UBIQUITINATION, AND INTERACTION WITH TRAF6. +RX PubMed=15456887; DOI=10.1128/mcb.24.20.9165-9175.2004; +RA Zhong J., Kyriakis J.M.; +RT "Germinal center kinase is required for optimal Jun N-terminal kinase +RT activation by Toll-like receptor agonists and is regulated by the ubiquitin +RT proteasome system and agonist-induced, TRAF6-dependent stabilization."; +RL Mol. Cell. Biol. 24:9165-9175(2004). +RN [9] +RP FUNCTION, AND INTERACTION WITH MAP3K11/MLK3. +RX PubMed=17584736; DOI=10.1074/jbc.m703422200; +RA Zhong J., Kyriakis J.M.; +RT "Dissection of a signaling pathway by which pathogen-associated molecular +RT patterns recruit the JNK and p38 MAPKs and trigger cytokine release."; +RL J. Biol. Chem. 282:24246-24254(2007). +RN [10] +RP REVIEW ON FUNCTION. +RX PubMed=10026130; DOI=10.1074/jbc.274.9.5259; +RA Kyriakis J.M.; +RT "Signaling by the germinal center kinase family of protein kinases."; +RL J. Biol. Chem. 274:5259-5262(1999). +RN [11] +RP REVIEW ON FUNCTION. +RX PubMed=11316611; DOI=10.1016/s0962-8924(01)01980-8; +RA Dan I., Watanabe N.M., Kusumi A.; +RT "The Ste20 group kinases as regulators of MAP kinase cascades."; +RL Trends Cell Biol. 11:220-230(2001). +RN [12] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, AND IDENTIFICATION BY +RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Cervix carcinoma; +RX PubMed=18669648; DOI=10.1073/pnas.0805139105; +RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., +RA Elledge S.J., Gygi S.P.; +RT "A quantitative atlas of mitotic phosphorylation."; +RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). +RN [13] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, AND IDENTIFICATION BY +RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; +RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., +RA Mann M., Daub H.; +RT "Large-scale proteomics analysis of the human kinome."; +RL Mol. Cell. Proteomics 8:1751-1764(2009). +RN [14] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, AND IDENTIFICATION BY +RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Leukemic T-cell; +RX PubMed=19690332; DOI=10.1126/scisignal.2000007; +RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., +RA Rodionov V., Han D.K.; +RT "Quantitative phosphoproteomic analysis of T cell receptor signaling +RT reveals system-wide modulation of protein-protein interactions."; +RL Sci. Signal. 2:RA46-RA46(2009). +RN [15] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328 AND SER-394, AND +RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Cervix carcinoma, and Erythroleukemia; +RX PubMed=23186163; DOI=10.1021/pr300630k; +RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., +RA Mohammed S.; +RT "Toward a comprehensive characterization of a human cancer cell +RT phosphoproteome."; +RL J. Proteome Res. 12:260-271(2013). +RN [16] +RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Liver; +RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; +RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., +RA Ye M., Zou H.; +RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver +RT phosphoproteome."; +RL J. Proteomics 96:253-262(2014). +CC -!- FUNCTION: Serine/threonine-protein kinase which acts as an essential +CC component of the MAP kinase signal transduction pathway. Acts as a MAPK +CC kinase kinase kinase (MAP4K) and is an upstream activator of the +CC stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) +CC signaling pathway and to a lesser extent of the p38 MAPKs signaling +CC pathway. Required for the efficient activation of JNKs by TRAF6- +CC dependent stimuli, including pathogen-associated molecular patterns +CC (PAMPs) such as polyinosine-polycytidine (poly(IC)), +CC lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial +CC flagellin. To a lesser degree, IL-1 and engagement of CD40 also +CC stimulate MAP4K2-mediated JNKs activation. The requirement for +CC MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS +CC stimulation of c-Jun phosphorylation and induction of IL-8. Enhances +CC MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 +CC autoinhibition and lead to activation following autophosphorylation. +CC Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling +CC pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. +CC May play a role in the regulation of vesicle targeting or fusion. +CC regulation of vesicle targeting or fusion. +CC {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, +CC ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:7477268, +CC ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- +CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- +CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, +CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; +CC Evidence={ECO:0000269|PubMed:7515885}; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- +CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, +CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; +CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:7515885}; +CC -!- COFACTOR: +CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; +CC Evidence={ECO:0000269|PubMed:7515885}; +CC -!- ACTIVITY REGULATION: The tumor necrosis factor (TNF), as well as +CC endotoxins and proinflammatory stimuli such as polyinosine-polycytidine +CC (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, +CC or lipid A activate MAP4K2 by promoting its autophosphorylation. +CC {ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:7477268}. +CC -!- SUBUNIT: Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3. +CC Interacts with RAB8A (By similarity). {ECO:0000250}. +CC -!- INTERACTION: +CC Q12851; Q13233: MAP3K1; NbExp=2; IntAct=EBI-49783, EBI-49776; +CC Q12851; Q9NUX5: POT1; NbExp=2; IntAct=EBI-49783, EBI-752420; +CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Basolateral cell +CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. +CC Golgi apparatus membrane {ECO:0000250}; Peripheral membrane protein +CC {ECO:0000250}. +CC -!- ALTERNATIVE PRODUCTS: +CC Event=Alternative splicing; Named isoforms=2; +CC Name=1; +CC IsoId=Q12851-1; Sequence=Displayed; +CC Name=2; +CC IsoId=Q12851-2; Sequence=VSP_054134; +CC -!- TISSUE SPECIFICITY: Highly expressed in germinal center but not mantle +CC zone B-cells. Also expressed in lung, brain and placenta and at lower +CC levels in other tissues examined. {ECO:0000269|PubMed:7515885}. +CC -!- DOMAIN: The PEST domains are Pro-, Glu-, Ser-, and Thr-rich domains. +CC Proteins with PEST domains are frequently targets of degradation by the +CC ubiquitin proteasome. {ECO:0000269|PubMed:7515885}. +CC -!- PTM: Polyubiquitinated through 'Lys-48'-polyubiquitin chains, allowing +CC proteasomal turnover. Ubiquitination requires the kinase activity of +CC MAP4K2/GCK. {ECO:0000269|PubMed:15456887}. +CC -!- PTM: Autophosphorylated in response to tumor necrosis factor (TNF), +CC endotoxins or proinflammatory stimuli. Autophosphorylation leads to +CC activation. +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr +CC protein kinase family. STE20 subfamily. {ECO:0000305}. +CC -!- SEQUENCE CAUTION: +CC Sequence=AAA20968.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AP001462; -; NOT_ANNOTATED_CDS; Genomic_DNA. +DR EMBL; CH471076; EAW74302.1; -; Genomic_DNA. +DR EMBL; BC047865; AAH47865.1; -; mRNA. +DR EMBL; U07349; AAA20968.1; ALT_SEQ; mRNA. +DR CCDS; CCDS8082.1; -. [Q12851-1] +DR CCDS; CCDS81582.1; -. [Q12851-2] +DR PIR; A53714; A53714. +DR RefSeq; NP_001294919.1; NM_001307990.1. [Q12851-2] +DR RefSeq; NP_004570.2; NM_004579.4. [Q12851-1] +DR SMR; Q12851; -. +DR BioGRID; 111809; 93. +DR IntAct; Q12851; 14. +DR MINT; Q12851; -. +DR STRING; 9606.ENSP00000294066; -. +DR BindingDB; Q12851; -. +DR ChEMBL; CHEMBL5330; -. +DR DrugBank; DB12010; Fostamatinib. +DR DrugCentral; Q12851; -. +DR GuidetoPHARMACOLOGY; 2086; -. +DR iPTMnet; Q12851; -. +DR PhosphoSitePlus; Q12851; -. +DR BioMuta; MAP4K2; -. +DR DMDM; 215274019; -. +DR CPTAC; CPTAC-862; -. +DR CPTAC; CPTAC-863; -. +DR EPD; Q12851; -. +DR jPOST; Q12851; -. +DR MassIVE; Q12851; -. +DR MaxQB; Q12851; -. +DR PaxDb; Q12851; -. +DR PeptideAtlas; Q12851; -. +DR PRIDE; Q12851; -. +DR ProteomicsDB; 58984; -. [Q12851-1] +DR ProteomicsDB; 70069; -. +DR Antibodypedia; 2060; 251 antibodies from 28 providers. +DR DNASU; 5871; -. +DR Ensembl; ENST00000294066; ENSP00000294066; ENSG00000168067. +DR Ensembl; ENST00000377350; ENSP00000366567; ENSG00000168067. [Q12851-2] +DR GeneID; 5871; -. +DR KEGG; hsa:5871; -. +DR MANE-Select; ENST00000294066.7; ENSP00000294066.2; NM_004579.5; NP_004570.2. +DR UCSC; uc001obh.4; human. [Q12851-1] +DR CTD; 5871; -. +DR DisGeNET; 5871; -. +DR GeneCards; MAP4K2; -. +DR HGNC; HGNC:6864; MAP4K2. +DR HPA; ENSG00000168067; Low tissue specificity. +DR MIM; 603166; gene. +DR neXtProt; NX_Q12851; -. +DR OpenTargets; ENSG00000168067; -. +DR PharmGKB; PA30610; -. +DR VEuPathDB; HostDB:ENSG00000168067; -. +DR eggNOG; KOG0576; Eukaryota. +DR GeneTree; ENSGT00940000162250; -. +DR InParanoid; Q12851; -. +DR OMA; AAITWIH; -. +DR OrthoDB; 996262at2759; -. +DR PhylomeDB; Q12851; -. +DR TreeFam; TF105121; -. +DR PathwayCommons; Q12851; -. +DR SignaLink; Q12851; -. +DR SIGNOR; Q12851; -. +DR BioGRID-ORCS; 5871; 29 hits in 1051 CRISPR screens. +DR GeneWiki; MAP4K2; -. +DR GenomeRNAi; 5871; -. +DR Pharos; Q12851; Tchem. +DR PRO; PR:Q12851; -. +DR Proteomes; UP000005640; Chromosome 11. +DR RNAct; Q12851; protein. +DR Bgee; ENSG00000168067; Expressed in blood and 176 other tissues. +DR ExpressionAtlas; Q12851; baseline and differential. +DR Genevisible; Q12851; HS. +DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell. +DR GO; GO:0000139; C:Golgi membrane; TAS:ProtInc. +DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. +DR GO; GO:0008349; F:MAP kinase kinase kinase kinase activity; IBA:GO_Central. +DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:UniProtKB. +DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. +DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:RHEA. +DR GO; GO:0006955; P:immune response; TAS:ProtInc. +DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. +DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. +DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc. +DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB. +DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:UniProtKB. +DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. +DR GO; GO:0006903; P:vesicle targeting; IEA:Ensembl. +DR InterPro; IPR001180; CNH_dom. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR021160; MAPKKKK. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR017441; Protein_kinase_ATP_BS. +DR Pfam; PF00780; CNH; 1. +DR Pfam; PF00069; Pkinase; 1. +DR PIRSF; PIRSF038172; MAPKKKK; 1. +DR SMART; SM00036; CNH; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS50219; CNH; 1. +DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +PE 1: Evidence at protein level; +KW Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; +KW Golgi apparatus; Immunity; Innate immunity; Kinase; Membrane; +KW Nucleotide-binding; Phosphoprotein; Reference proteome; +KW Serine/threonine-protein kinase; Stress response; Transferase; +KW Ubl conjugation. +FT CHAIN 1..820 +FT /note="Mitogen-activated protein kinase kinase kinase +FT kinase 2" +FT /id="PRO_0000086275" +FT DOMAIN 16..273 +FT /note="Protein kinase" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT DOMAIN 482..793 +FT /note="CNH" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795" +FT NP_BIND 22..30 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT REGION 294..314 +FT /note="PEST1" +FT REGION 344..360 +FT /note="PEST2" +FT REGION 387..442 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 405..448 +FT /note="PEST3" +FT COMPBIAS 409..438 +FT /note="Pro residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT ACT_SITE 136 +FT /note="Proton acceptor" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT BINDING 45 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT MOD_RES 328 +FT /note="Phosphoserine" +FT /evidence="ECO:0007744|PubMed:23186163" +FT MOD_RES 394 +FT /note="Phosphoserine" +FT /evidence="ECO:0007744|PubMed:18669648, +FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, +FT ECO:0007744|PubMed:23186163" +FT VAR_SEQ 426..433 +FT /note="Missing (in isoform 2)" +FT /evidence="ECO:0000303|PubMed:15489334" +FT /id="VSP_054134" +FT CONFLICT 120 +FT /note="A -> R (in Ref. 4; AAA20968)" +FT /evidence="ECO:0000305" +SQ SEQUENCE 820 AA; 91556 MW; A59C1E99BFFAEF41 CRC64; + MALLRDVSLQ DPRDRFELLQ RVGAGTYGDV YKARDTVTSE LAAVKIVKLD PGDDISSLQQ + EITILRECRH PNVVAYIGSY LRNDRLWICM EFCGGGSLQE IYHATGPLEE RQIAYVCREA + LKGLHHLHSQ GKIHRDIKGA NLLLTLQGDV KLADFGVSGE LTASVAKRRS FIGTPYWMAP + EVAAVERKGG YNELCDVWAL GITAIELGEL QPPLFHLHPM RALMLMSKSS FQPPKLRDKT + RWTQNFHHFL KLALTKNPKK RPTAEKLLQH PFTTQQLPRA LLTQLLDKAS DPHLGTPSPE + DCELETYDMF PDTIHSRGQH GPAERTPSEI QFHQVKFGAP RRKETDPLNE PWEEEWTLLG + KEELSGSLLQ SVQEALEERS LTIRSASEFQ ELDSPDDTMG TIKRAPFLGP LPTDPPAEEP + LSSPPGTLPP PPSGPNSSPL LPTAWATMKQ REDPERSSCH GLPPTPKVHM GACFSKVFNG + CPLRIHAAVT WIHPVTRDQF LVVGAEEGIY TLNLHELHED TLEKLISHRC SWLYCVNNVL + LSLSGKSTHI WAHDLPGLFE QRRLQQQVPL SIPTNRLTQR IIPRRFALST KIPDTKGCLQ + CRVVRNPYTG ATFLLAALPT SLLLLQWYEP LQKFLLLKNF SSPLPSPAGM LEPLVLDGKE + LPQVCVGAEG PEGPGCRVLF HVLPLEAGLT PDILIPPEGI PGSAQQVIQV DRDTILVSFE + RCVRIVNMQG EPTATLAPEL TFDFPIETVV CLQDSVLAFW SHGMQGRSLD TNEVTQEITD + ETRIFRVLGA HRDIILESIP TDNPEAHSNL YILTGHQSTY +// +ID MP2K4_MOUSE Reviewed; 397 AA. +AC P47809; +DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. +DT 01-NOV-1997, sequence version 2. +DT 23-FEB-2022, entry version 176. +DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 4; +DE Short=MAP kinase kinase 4; +DE Short=MAPKK 4; +DE EC=2.7.12.2; +DE AltName: Full=C-JUN N-terminal kinase kinase 1; +DE Short=JNK kinase 1; +DE Short=JNKK 1; +DE AltName: Full=JNK-activating kinase 1; +DE AltName: Full=MAPK/ERK kinase 4; +DE Short=MEK 4; +DE AltName: Full=SAPK/ERK kinase 1; +DE Short=SEK1; +GN Name=Map2k4; Synonyms=Jnkk1, Mek4, Mkk4, Prkmk4, Sek1, Serk1, Skk1; +OS Mus musculus (Mouse). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; +OC Murinae; Mus; Mus. +OX NCBI_TaxID=10090; +RN [1] +RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF LYS-129. +RC TISSUE=Embryo; +RX PubMed=7997269; DOI=10.1038/372794a0; +RA Sanchez I., Hughes R.T., Mayer B.J., Yee K., Woodgett J.R., Avruch J., +RA Kyriakis J.M., Zon L.I.; +RT "Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating +RT transcription factor c-Jun."; +RL Nature 372:794-798(1994). +RN [2] +RP SEQUENCE REVISION. +RA Zon L.I.; +RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases. +RN [3] +RP FUNCTION. +RX PubMed=9620683; DOI=10.1016/s1074-7613(00)80567-1; +RA Swat W., Fujikawa K., Ganiatsas S., Yang D., Xavier R.J., Harris N.L., +RA Davidson L., Ferrini R., Davis R.J., Labow M.A., Flavell R.A., Zon L.I., +RA Alt F.W.; +RT "SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid +RT compartment but not for lymphocyte development."; +RL Immunity 8:625-634(1998). +RN [4] +RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND FUNCTION OF THE MKK/JNK +RP PATHWAY. +RX PubMed=9891090; DOI=10.1128/mcb.19.2.1569; +RA Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J.; +RT "The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases."; +RL Mol. Cell. Biol. 19:1569-1581(1999). +RN [5] +RP TISSUE SPECIFICITY. +RX PubMed=10095085; DOI=10.1016/s0169-328x(99)00035-2; +RA Lee J.K., Hwang W.S., Lee Y.D., Han P.L.; +RT "Dynamic expression of SEK1 suggests multiple roles of the gene during +RT embryogenesis and in adult brain of mice."; +RL Brain Res. Mol. Brain Res. 66:133-140(1999). +RN [6] +RP FUNCTION. +RX PubMed=11390361; DOI=10.1101/gad.888501; +RA Tournier C., Dong C., Turner T.K., Jones S.N., Flavell R.A., Davis R.J.; +RT "MKK7 is an essential component of the JNK signal transduction pathway +RT activated by proinflammatory cytokines."; +RL Genes Dev. 15:1419-1426(2001). +RN [7] +RP PHOSPHORYLATION, AND INTERACTION WITH MAP3K1/MEKK1. +RX PubMed=12401521; DOI=10.1016/s0898-6568(02)00056-6; +RA Tu Z., Mooney S.M., Lee F.S.; +RT "A subdomain of MEKK1 that is critical for binding to MKK4."; +RL Cell. Signal. 15:65-77(2003). +RN [8] +RP FUNCTION. +RX PubMed=12624093; DOI=10.1074/jbc.m213182200; +RA Kishimoto H., Nakagawa K., Watanabe T., Kitagawa D., Momose H., Seo J., +RA Nishitai G., Shimizu N., Ohata S., Tanemura S., Asaka S., Goto T., +RA Fukushi H., Yoshida H., Suzuki A., Sasaki T., Wada T., Penninger J.M., +RA Nishina H., Katada T.; +RT "Different properties of SEK1 and MKK7 in dual phosphorylation of stress- +RT induced activated protein kinase SAPK/JNK in embryonic stem cells."; +RL J. Biol. Chem. 278:16595-16601(2003). +RN [9] +RP DISRUPTION PHENOTYPE. +RX PubMed=17875933; DOI=10.1128/mcb.00226-07; +RA Wang X., Nadarajah B., Robinson A.C., McColl B.W., Jin J.W., +RA Dajas-Bailador F., Boot-Handford R.P., Tournier C.; +RT "Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in +RT the nervous system causes severe brain developmental defects and premature +RT death."; +RL Mol. Cell. Biol. 27:7935-7946(2007). +RN [10] +RP DISRUPTION PHENOTYPE. +RX PubMed=19265040; DOI=10.1161/circresaha.108.188292; +RA Liu W., Zi M., Jin J., Prehar S., Oceandy D., Kimura T.E., Lei M., +RA Neyses L., Weston A.H., Cartwright E.J., Wang X.; +RT "Cardiac-specific deletion of mkk4 reveals its role in pathological +RT hypertrophic remodeling but not in physiological cardiac growth."; +RL Circ. Res. 104:905-914(2009). +RN [11] +RP REVIEW ON ACTIVITY REGULATION. +RX PubMed=17496909; DOI=10.1038/sj.onc.1210392; +RA Raman M., Chen W., Cobb M.H.; +RT "Differential regulation and properties of MAPKs."; +RL Oncogene 26:3100-3112(2007). +RN [12] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-255 AND THR-259, AND +RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, +RC Spleen, and Testis; +RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; +RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., +RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; +RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; +RL Cell 143:1174-1189(2010). +RN [13] +RP REVIEW ON FUNCTION. +RX PubMed=20801953; DOI=10.1093/jb/mvq098; +RA Asaoka Y., Nishina H.; +RT "Diverse physiological functions of MKK4 and MKK7 during early +RT embryogenesis."; +RL J. Biochem. 148:393-401(2010). +RN [14] +RP REVIEW ON REGULATION, AND REVIEW ON FUNCTION. +RX PubMed=21333379; DOI=10.1016/j.ejcb.2010.11.008; +RA Haeusgen W., Herdegen T., Waetzig V.; +RT "The bottleneck of JNK signaling: molecular and functional characteristics +RT of MKK4 and MKK7."; +RL Eur. J. Cell Biol. 90:536-544(2011). +RN [15] +RP INTERACTION WITH SPAG9. +RX PubMed=12391307; DOI=10.1073/pnas.232310199; +RA Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.; +RT "JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and +RT transcription factors."; +RL Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002). +RN [16] +RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-56, AND IDENTIFICATION BY MASS +RP SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Brain, and Embryo; +RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; +RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., +RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., +RA Bedford M.T., Comb M.J.; +RT "Immunoaffinity enrichment and mass spectrometry analysis of protein +RT methylation."; +RL Mol. Cell. Proteomics 13:372-387(2014). +CC -!- FUNCTION: Dual specificity protein kinase which acts as an essential +CC component of the MAP kinase signal transduction pathway. Essential +CC component of the stress-activated protein kinase/c-Jun N-terminal +CC kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the +CC only known kinase to directly activate the stress-activated protein +CC kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. +CC MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, +CC but they differ in their preference for the phosphorylation site in the +CC Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the +CC Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of +CC the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK +CC activation at least in response to proinflammatory cytokines, while +CC other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which +CC synergistically phosphorylate JNKs. MAP2K4 is required for maintaining +CC peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also +CC involved in mitochondrial death signaling pathway, including the +CC release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 +CC exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 +CC MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:11390361, +CC ECO:0000269|PubMed:12624093, ECO:0000269|PubMed:7997269, +CC ECO:0000269|PubMed:9620683, ECO:0000269|PubMed:9891090}. +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- +CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- +CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, +CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.2; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- +CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, +CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; +CC EC=2.7.12.2; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- +CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- +CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, +CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2; +CC -!- ACTIVITY REGULATION: Activated in response to a variety of cellular +CC stresses, including UV and gamma-irradiation, heat shock, +CC hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory +CC cytokines. Also activated by developmental cues. MAP2K4/MKK4 is +CC activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, +CC MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK. +CC {ECO:0000269|PubMed:9891090}. +CC -!- SUBUNIT: Interacts with SPAG9. Interacts (via its D domain) with its +CC substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14 (By +CC similarity). Interacts (via its DVD domain) with MAP3Ks activators like +CC MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and +CC MAPK8IP3/JIP3 (By similarity). {ECO:0000250}. +CC -!- INTERACTION: +CC P47809; P53349: Map3k1; NbExp=2; IntAct=EBI-447934, EBI-447913; +CC P47809; Q9ESN9-2: Mapk8ip3; NbExp=3; IntAct=EBI-447934, EBI-9549291; +CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9891090}. Nucleus +CC {ECO:0000269|PubMed:9891090}. +CC -!- TISSUE SPECIFICITY: Strong expression is detected in most of the +CC central nervous system and in liver and thymus during early stages of +CC development. While expression in nervous system increases over time, +CC expression in fetal liver and thymus gradually decreases as +CC embryogenesis proceeds. High level of expression in the central nervous +CC system persists throughout postnatal development and remained at a +CC stable level in adult brain. {ECO:0000269|PubMed:10095085}. +CC -!- DOMAIN: The DVD domain (residues 362-385) contains a conserved docking +CC site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD +CC sites bind to their specific upstream MAP kinase kinase kinases +CC (MAP3Ks) and are essential for activation (By similarity). +CC {ECO:0000250}. +CC -!- DOMAIN: The D domain (residues 35-50) contains a conserved docking site +CC and is required for the binding to MAPk substrates. +CC -!- PTM: Activated by phosphorylation on Ser-255 and Thr-259 by MAP kinase +CC kinase kinases (MAP3Ks). {ECO:0000250}. +CC -!- DISRUPTION PHENOTYPE: Causes irregular alignment of Purkinje cells in +CC the cerebellum and delayed radial migration in the cortex during brain +CC development. The cardiac-specific deletion prevents pathological +CC cardiac hypertrophy. {ECO:0000269|PubMed:17875933, +CC ECO:0000269|PubMed:19265040}. +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr +CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; U18310; AAB81554.1; -; mRNA. +DR CCDS; CCDS24844.1; -. +DR PIR; S52423; S52423. +DR RefSeq; NP_033183.1; NM_009157.5. +DR SMR; P47809; -. +DR BioGRID; 204952; 17. +DR CORUM; P47809; -. +DR DIP; DIP-869N; -. +DR IntAct; P47809; 4. +DR STRING; 10090.ENSMUSP00000041282; -. +DR ChEMBL; CHEMBL2201; -. +DR iPTMnet; P47809; -. +DR PhosphoSitePlus; P47809; -. +DR EPD; P47809; -. +DR jPOST; P47809; -. +DR PaxDb; P47809; -. +DR PeptideAtlas; P47809; -. +DR PRIDE; P47809; -. +DR ProteomicsDB; 295582; -. +DR Antibodypedia; 3571; 1402 antibodies from 42 providers. +DR DNASU; 26398; -. +DR Ensembl; ENSMUST00000046963; ENSMUSP00000041282; ENSMUSG00000033352. +DR GeneID; 26398; -. +DR KEGG; mmu:26398; -. +DR UCSC; uc007jlb.1; mouse. +DR CTD; 6416; -. +DR MGI; MGI:1346869; Map2k4. +DR VEuPathDB; HostDB:ENSMUSG00000033352; -. +DR eggNOG; KOG1006; Eukaryota. +DR GeneTree; ENSGT00940000154744; -. +DR HOGENOM; CLU_000288_63_23_1; -. +DR InParanoid; P47809; -. +DR OMA; KQRHIPE; -. +DR PhylomeDB; P47809; -. +DR TreeFam; TF350701; -. +DR BRENDA; 2.7.12.2; 3474. +DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence. +DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation. +DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. +DR BioGRID-ORCS; 26398; 5 hits in 64 CRISPR screens. +DR ChiTaRS; Map2k4; mouse. +DR PRO; PR:P47809; -. +DR Proteomes; UP000000589; Chromosome 11. +DR RNAct; P47809; protein. +DR Bgee; ENSMUSG00000033352; Expressed in frontal cortex and 332 other tissues. +DR ExpressionAtlas; P47809; baseline and differential. +DR Genevisible; P47809; MM. +DR GO; GO:0030424; C:axon; ISO:MGI. +DR GO; GO:0005829; C:cytosol; ISO:MGI. +DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI. +DR GO; GO:0005634; C:nucleus; ISO:MGI. +DR GO; GO:0043204; C:perikaryon; ISO:MGI. +DR GO; GO:0005524; F:ATP binding; ISO:MGI. +DR GO; GO:0008545; F:JUN kinase kinase activity; ISO:MGI. +DR GO; GO:0004708; F:MAP kinase kinase activity; ISO:MGI. +DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI. +DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. +DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; ISO:MGI. +DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. +DR GO; GO:0007254; P:JNK cascade; ISO:MGI. +DR GO; GO:0000165; P:MAPK cascade; IPI:MGI. +DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IMP:MGI. +DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. +DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI. +DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI. +DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI. +DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI. +DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISO:MGI. +DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI. +DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IDA:BHF-UCL. +DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI. +DR GO; GO:0009611; P:response to wounding; IMP:MGI. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR017441; Protein_kinase_ATP_BS. +DR InterPro; IPR008271; Ser/Thr_kinase_AS. +DR Pfam; PF00069; Pkinase; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. +PE 1: Evidence at protein level; +KW Acetylation; Apoptosis; ATP-binding; Cytoplasm; Kinase; Methylation; +KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; +KW Serine/threonine-protein kinase; Stress response; Transferase; +KW Tyrosine-protein kinase. +FT INIT_MET 1 +FT /note="Removed" +FT /evidence="ECO:0000250|UniProtKB:P45985" +FT CHAIN 2..397 +FT /note="Dual specificity mitogen-activated protein kinase +FT kinase 4" +FT /id="PRO_0000086382" +FT DOMAIN 100..366 +FT /note="Protein kinase" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT NP_BIND 106..114 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT REGION 1..38 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 35..50 +FT /note="D domain" +FT /evidence="ECO:0000250" +FT REGION 362..385 +FT /note="DVD domain" +FT /evidence="ECO:0000250" +FT ACT_SITE 227 +FT /note="Proton acceptor" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, +FT ECO:0000255|PROSITE-ProRule:PRU10027" +FT BINDING 129 +FT /note="ATP" +FT MOD_RES 2 +FT /note="N-acetylalanine" +FT /evidence="ECO:0000250|UniProtKB:P45985" +FT MOD_RES 56 +FT /note="Asymmetric dimethylarginine; alternate" +FT /evidence="ECO:0007744|PubMed:24129315" +FT MOD_RES 56 +FT /note="Omega-N-methylarginine; alternate" +FT /evidence="ECO:0000250|UniProtKB:P45985" +FT MOD_RES 88 +FT /note="Phosphoserine" +FT /evidence="ECO:0007744|PubMed:21183079" +FT MOD_RES 255 +FT /note="Phosphoserine" +FT /evidence="ECO:0007744|PubMed:21183079" +FT MOD_RES 259 +FT /note="Phosphothreonine" +FT /evidence="ECO:0007744|PubMed:21183079" +FT MUTAGEN 129 +FT /note="K->R: Loss of ATP-binding." +FT /evidence="ECO:0000269|PubMed:7997269" +SQ SEQUENCE 397 AA; 44114 MW; B99C6688184E5B3D CRC64; + MAAPSPSGGG GSGGGGGTPG PIGPPASGHP AVSSMQGKRK ALKLNFANPP VKSTARFTLN + PNTTGVQNPH IERLRTHSIE SSGKLKISPE QHWDFTAEDL KDLGEIGRGA YGSVNKMVHK + PSGQIMAVKR IRSTVDEKEQ KQLLMDLDVV MRSSDCPYIV QFYGALFREG DCWICMELMS + TSFDKFYKYV YSVLDDVIPE EILGKITLAT VKALNHLKEN LKIIHRDIKP SNILLDRSGN + IKLCDFGISG QLVDSIAKTR DAGCRPYMAP ERIDPSASRQ GYDVRSDVWS LGITLYELAT + GRFPYPKWNS VFDQLTQVVK GDPPQLSNSE EREFSPSFIN FVNLCLTKDE SKRPKYKELL + KHPFILMYEE RTVEVACYVC KILDQMPATP SSPMYVD +// +ID MP2K7_HUMAN Reviewed; 419 AA. +AC O14733; B2R9S5; D6W659; O14648; O14816; O60452; O60453; Q1PG43; Q8IY10; +DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. +DT 30-MAY-2000, sequence version 2. +DT 23-FEB-2022, entry version 207. +DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 7; +DE Short=MAP kinase kinase 7; +DE Short=MAPKK 7; +DE EC=2.7.12.2; +DE AltName: Full=JNK-activating kinase 2; +DE AltName: Full=MAPK/ERK kinase 7; +DE Short=MEK 7; +DE AltName: Full=Stress-activated protein kinase kinase 4; +DE Short=SAPK kinase 4; +DE Short=SAPKK-4; +DE Short=SAPKK4; +DE AltName: Full=c-Jun N-terminal kinase kinase 2; +DE Short=JNK kinase 2; +DE Short=JNKK 2; +GN Name=MAP2K7; Synonyms=JNKK2, MEK7, MKK7, PRKMK7, SKK4; +OS Homo sapiens (Human). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; +OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; +OC Homo. +OX NCBI_TaxID=9606; +RN [1] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY. +RC TISSUE=Heart, and Skeletal muscle; +RX PubMed=9372971; DOI=10.1128/mcb.17.12.7407; +RA Wu Z., Wu J., Jacinto E., Karin M.; +RT "Molecular cloning and characterization of human JNKK2, a novel jun NH2- +RT terminal kinase-specific kinase."; +RL Mol. Cell. Biol. 17:7407-7416(1997). +RN [2] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND ACTIVITY REGULATION. +RX PubMed=9312068; DOI=10.1074/jbc.272.40.24751; +RA Lu X., Nemoto S., Lin A.; +RT "Identification of c-Jun NH2-terminal protein kinase (JNK)-activating +RT kinase 2 as an activator of JNK but not p38."; +RL J. Biol. Chem. 272:24751-24754(1997). +RN [3] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE +RP SPECIFICITY, AND VARIANT PHE-259. +RC TISSUE=Fetal kidney; +RX PubMed=9535930; DOI=10.1074/jbc.273.15.9344; +RA Foltz I.N., Gerl R.E., Wieler J.S., Luckach M., Salmon R.A., Schrader J.W.; +RT "Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly +RT conserved c-Jun N-terminal kinase/stress-activated protein kinase +RT (JNK/SAPK) activated by environmental stresses and physiological stimuli."; +RL J. Biol. Chem. 273:9344-9351(1998). +RN [4] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ACTIVITY REGULATION, AND TISSUE +RP SPECIFICITY. +RX PubMed=16442502; DOI=10.1016/j.bbrc.2005.12.223; +RA Michael L., Swantek J., Robinson M.J.; +RT "Cloning and expression of human mitogen-activated protein kinase kinase +RT 7gamma1."; +RL Biochem. Biophys. Res. Commun. 341:679-683(2006). +RN [5] +RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION IN PHOSPHORYLATION OF +RP MAPK8/JNK1 AND MAPK9/JNK2. +RA Yang J., New L., Yong J., Han J., Su B.; +RT "Molecular cloning of human JNKK2 reveals a novel kinase module for c-Jun +RT N-terminal kinase activation."; +RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. +RN [6] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). +RC TISSUE=Brain; +RX PubMed=14702039; DOI=10.1038/ng1285; +RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., +RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., +RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., +RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., +RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., +RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., +RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., +RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., +RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., +RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., +RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., +RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., +RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., +RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., +RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., +RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., +RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., +RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., +RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., +RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., +RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., +RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., +RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., +RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., +RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., +RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., +RA Isogai T., Sugano S.; +RT "Complete sequencing and characterization of 21,243 full-length human +RT cDNAs."; +RL Nat. Genet. 36:40-45(2004). +RN [7] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., +RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., +RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., +RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., +RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., +RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., +RA Hunkapiller M.W., Myers E.W., Venter J.C.; +RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. +RN [8] +RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). +RC TISSUE=Testis; +RX PubMed=15489334; DOI=10.1101/gr.2596504; +RG The MGC Project Team; +RT "The status, quality, and expansion of the NIH full-length cDNA project: +RT the Mammalian Gene Collection (MGC)."; +RL Genome Res. 14:2121-2127(2004). +RN [9] +RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-260 (ISOFORMS 1/4). +RX PubMed=9207092; DOI=10.1073/pnas.94.14.7337; +RA Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J.; +RT "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun +RT NH2-terminal kinase."; +RL Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997). +RN [10] +RP INTERACTION WITH MAPK8IP1/JIP1 AND MAPK8IP2/JIP2. +RX PubMed=10490659; DOI=10.1128/mcb.19.10.7245; +RA Yasuda J., Whitmarsh A.J., Cavanagh J., Sharma M., Davis R.J.; +RT "The JIP group of mitogen-activated protein kinase scaffold proteins."; +RL Mol. Cell. Biol. 19:7245-7254(1999). +RN [11] +RP CLEAVAGE BY ANTHRAX LETHAL FACTOR. +RX PubMed=11104681; DOI=10.1042/bj3520739; +RA Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.; +RT "Susceptibility of mitogen-activated protein kinase kinase family members +RT to proteolysis by anthrax lethal factor."; +RL Biochem. J. 352:739-745(2000). +RN [12] +RP INTERACTION WITH MAPK8IP3/JIP3. +RX PubMed=12189133; DOI=10.1074/jbc.m202004200; +RA Matsuura H., Nishitoh H., Takeda K., Matsuzawa A., Amagasa T., Ito M., +RA Yoshioka K., Ichijo H.; +RT "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK +RT signaling pathway. A new mode of regulation of the MAP kinase cascade."; +RL J. Biol. Chem. 277:40703-40709(2002). +RN [13] +RP DOMAIN. +RX PubMed=15866172; DOI=10.1016/j.molcel.2005.04.001; +RA Takekawa M., Tatebayashi K., Saito H.; +RT "Conserved docking site is essential for activation of mammalian MAP kinase +RT kinases by specific MAP kinase kinase kinases."; +RL Mol. Cell 18:295-306(2005). +RN [14] +RP INTERACTION WITH VRK2. +RX PubMed=18286207; DOI=10.1371/journal.pone.0001660; +RA Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A.; +RT "Modulation of interleukin-1 transcriptional response by the interaction +RT between VRK2 and the JIP1 scaffold protein."; +RL PLoS ONE 3:E1660-E1660(2008). +RN [15] +RP REVIEW ON ACTIVITY REGULATION. +RX PubMed=17496909; DOI=10.1038/sj.onc.1210392; +RA Raman M., Chen W., Cobb M.H.; +RT "Differential regulation and properties of MAPKs."; +RL Oncogene 26:3100-3112(2007). +RN [16] +RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR +RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY +RP [LARGE SCALE ANALYSIS]. +RX PubMed=19413330; DOI=10.1021/ac9004309; +RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; +RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a +RT refined SCX-based approach."; +RL Anal. Chem. 81:4493-4501(2009). +RN [17] +RP REVIEW ON FUNCTION. +RX PubMed=20801953; DOI=10.1093/jb/mvq098; +RA Asaoka Y., Nishina H.; +RT "Diverse physiological functions of MKK4 and MKK7 during early +RT embryogenesis."; +RL J. Biochem. 148:393-401(2010). +RN [18] +RP INTERACTION WITH RASSF7. +RX PubMed=21278800; DOI=10.1038/cdd.2010.137; +RA Takahashi S., Ebihara A., Kajiho H., Kontani K., Nishina H., Katada T.; +RT "RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the +RT activity of phosphorylated-MKK7."; +RL Cell Death Differ. 18:645-655(2011). +RN [19] +RP REVIEW ON REGULATION, AND REVIEW ON FUNCTION. +RX PubMed=21333379; DOI=10.1016/j.ejcb.2010.11.008; +RA Haeusgen W., Herdegen T., Waetzig V.; +RT "The bottleneck of JNK signaling: molecular and functional characteristics +RT of MKK4 and MKK7."; +RL Eur. J. Cell Biol. 90:536-544(2011). +RN [20] +RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR +RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY +RP [LARGE SCALE ANALYSIS]. +RX PubMed=22814378; DOI=10.1073/pnas.1210303109; +RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., +RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., +RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; +RT "N-terminal acetylome analyses and functional insights of the N-terminal +RT acetyltransferase NatB."; +RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). +RN [21] +RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY +RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. +RC TISSUE=Erythroleukemia; +RX PubMed=23186163; DOI=10.1021/pr300630k; +RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., +RA Mohammed S.; +RT "Toward a comprehensive characterization of a human cancer cell +RT phosphoproteome."; +RL J. Proteome Res. 12:260-271(2013). +RN [22] +RP FUNCTION. +RX PubMed=28111074; DOI=10.1016/j.cell.2016.12.044; +RA Huang Y.A., Zhou B., Wernig M., Suedhof T.C.; +RT "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and +RT Abeta Secretion."; +RL Cell 168:427-441(2017). +RN [23] +RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 101-405. +RG RIKEN structural genomics initiative (RSGI); +RT "Crystal structure of human mitogen-activated protein kinase kinase 7 +RT activated mutant (s287d, t291d)."; +RL Submitted (FEB-2009) to the PDB data bank. +RN [24] +RP VARIANTS [LARGE SCALE ANALYSIS] SER-118; CYS-138; CYS-162; HIS-162 AND +RP THR-195. +RX PubMed=17344846; DOI=10.1038/nature05610; +RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., +RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., +RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., +RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., +RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., +RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., +RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., +RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., +RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., +RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., +RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., +RA Futreal P.A., Stratton M.R.; +RT "Patterns of somatic mutation in human cancer genomes."; +RL Nature 446:153-158(2007). +CC -!- FUNCTION: Dual specificity protein kinase which acts as an essential +CC component of the MAP kinase signal transduction pathway. Essential +CC component of the stress-activated protein kinase/c-Jun N-terminal +CC kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the +CC only known kinase to directly activate the stress-activated protein +CC kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. +CC MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, +CC but they differ in their preference for the phosphorylation site in the +CC Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of +CC the Tyr residue and MAP2K7/MKK7 for the Thr residue. The +CC monophosphorylation of JNKs on the Thr residue is sufficient to +CC increase JNK activity indicating that MAP2K7/MKK7 is important to +CC trigger JNK activity, while the additional phosphorylation of the Tyr +CC residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific +CC role in JNK signal transduction pathway activated by proinflammatory +CC cytokines. The MKK/JNK signaling pathway is also involved in +CC mitochondrial death signaling pathway, including the release cytochrome +CC c, leading to apoptosis. Part of a non-canonical MAPK signaling +CC pathway, composed of the upstream MAP3K12 kinase and downstream MAP +CC kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated +CC transcription of APP in response to APOE (PubMed:28111074). +CC {ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:9312068, +CC ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, +CC ECO:0000269|Ref.5}. +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- +CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- +CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, +CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.2; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- +CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, +CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; +CC EC=2.7.12.2; +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- +CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- +CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, +CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2; +CC -!- COFACTOR: +CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; +CC -!- ACTIVITY REGULATION: Activated by phosphorylation by specific MAP +CC kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 +CC and MAP3K12/DLK. {ECO:0000269|PubMed:16442502, +CC ECO:0000269|PubMed:9312068}. +CC -!- SUBUNIT: Interacts with isoform 1 of VRK2. Interacts (via its D domain) +CC with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By +CC similarity). Interacts (via its DVD domain) with MAP3Ks activators like +CC MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity). Interacts with +CC MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. +CC Interacts with RASSF7, the interaction promotes phosphorylation. Found +CC in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAPK8IP1/JIP1 and +CC MAPK8/JNK1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, +CC MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). +CC {ECO:0000250|UniProtKB:Q8CE90, ECO:0000269|PubMed:10490659, +CC ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:18286207, +CC ECO:0000269|PubMed:21278800}. +CC -!- INTERACTION: +CC O14733; O15519-1: CFLAR; NbExp=2; IntAct=EBI-492605, EBI-4567563; +CC O14733; O75293: GADD45B; NbExp=8; IntAct=EBI-492605, EBI-448187; +CC O14733; Q5S007: LRRK2; NbExp=3; IntAct=EBI-492605, EBI-5323863; +CC O14733; O43318: MAP3K7; NbExp=3; IntAct=EBI-492605, EBI-358684; +CC O14733; Q9UQF2: MAPK8IP1; NbExp=5; IntAct=EBI-492605, EBI-78404; +CC O14733-2; P45983: MAPK8; NbExp=3; IntAct=EBI-492627, EBI-286483; +CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. +CC -!- ALTERNATIVE PRODUCTS: +CC Event=Alternative splicing; Named isoforms=4; +CC Name=1; Synonyms=A; +CC IsoId=O14733-1; Sequence=Displayed; +CC Name=2; Synonyms=B; +CC IsoId=O14733-2; Sequence=VSP_004883; +CC Name=3; Synonyms=gamma1; +CC IsoId=O14733-3; Sequence=VSP_022309; +CC Name=4; +CC IsoId=O14733-4; Sequence=VSP_022310; +CC -!- TISSUE SPECIFICITY: Ubiquitous; with highest level of expression in +CC skeletal muscle. Isoform 3 is found at low levels in placenta, fetal +CC liver, and skeletal muscle. {ECO:0000269|PubMed:16442502, +CC ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930}. +CC -!- DOMAIN: The DVD domain (residues 377-400) contains a conserved docking +CC site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD +CC sites bind to their specific upstream MAP kinase kinase kinases +CC (MAP3Ks) and are essential for activation. +CC {ECO:0000269|PubMed:15866172}. +CC -!- DOMAIN: The D domain (residues 37-57) contains a conserved docking site +CC and is required for the binding to MAPK substrates. +CC {ECO:0000269|PubMed:15866172}. +CC -!- PTM: Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase +CC kinase kinases (MAP3Ks). {ECO:0000250}. +CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention. +CC {ECO:0000305}. +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr +CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}. +CC -!- SEQUENCE CAUTION: +CC Sequence=AAB97813.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305}; +CC Sequence=AAB97813.1; Type=Frameshift; Evidence={ECO:0000305}; +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AF014401; AAB88048.1; -; mRNA. +DR EMBL; AF006689; AAB97813.1; ALT_SEQ; mRNA. +DR EMBL; AF013588; AAC16272.1; -; mRNA. +DR EMBL; AF013589; AAC16273.1; -; mRNA. +DR EMBL; DQ445915; ABE03013.1; -; mRNA. +DR EMBL; AF022805; AAC26142.1; -; mRNA. +DR EMBL; AK313899; BAG36622.1; -; mRNA. +DR EMBL; CH471139; EAW68964.1; -; Genomic_DNA. +DR EMBL; CH471139; EAW68968.1; -; Genomic_DNA. +DR EMBL; BC038295; AAH38295.1; -; mRNA. +DR EMBL; AF003199; AAB63374.1; -; mRNA. +DR CCDS; CCDS42491.1; -. [O14733-1] +DR CCDS; CCDS74277.1; -. [O14733-3] +DR CCDS; CCDS74278.1; -. [O14733-4] +DR RefSeq; NP_001284484.1; NM_001297555.1. [O14733-3] +DR RefSeq; NP_001284485.1; NM_001297556.1. [O14733-4] +DR RefSeq; NP_660186.1; NM_145185.3. [O14733-1] +DR PDB; 2DYL; X-ray; 2.45 A; A=101-405. +DR PDB; 3WZU; X-ray; 3.01 A; A=103-419. +DR PDB; 4UX9; X-ray; 2.34 A; F/G/H/I=37-48. +DR PDB; 5B2K; X-ray; 2.75 A; A=103-419. +DR PDB; 5B2L; X-ray; 2.10 A; A=103-419. +DR PDB; 5B2M; X-ray; 3.06 A; A=103-419. +DR PDB; 5Y8U; X-ray; 2.92 A; A=103-419. +DR PDB; 5Y90; X-ray; 1.30 A; A=103-419. +DR PDB; 5Z1D; X-ray; 2.28 A; A=102-419. +DR PDB; 5Z1E; X-ray; 2.30 A; A=102-419. +DR PDB; 6IB0; X-ray; 2.60 A; A=101-408. +DR PDB; 6IB2; X-ray; 2.10 A; A=101-408. +DR PDB; 6QFL; X-ray; 2.20 A; A=101-408. +DR PDB; 6QFR; X-ray; 2.30 A; A=101-408. +DR PDB; 6QFT; X-ray; 2.70 A; A=101-408. +DR PDB; 6QG4; X-ray; 2.30 A; A=111-408. +DR PDB; 6QG7; X-ray; 2.10 A; A=101-408. +DR PDB; 6QHO; X-ray; 2.70 A; A=111-408. +DR PDB; 6QHR; X-ray; 2.52 A; A=111-408. +DR PDB; 6YFZ; X-ray; 1.90 A; A=100-405. +DR PDB; 6YG0; X-ray; 2.00 A; A=100-405. +DR PDB; 6YG1; X-ray; 2.22 A; A/B/C=60-405. +DR PDB; 6YG2; X-ray; 2.00 A; A=100-405. +DR PDB; 6YG3; X-ray; 2.05 A; A=100-405. +DR PDB; 6YG4; X-ray; 2.30 A; A=100-405. +DR PDB; 6YG5; X-ray; 2.40 A; A=100-405. +DR PDB; 6YG6; X-ray; 2.15 A; A/B=100-405. +DR PDB; 6YG7; X-ray; 2.20 A; A/B=100-405. +DR PDB; 6YZ4; X-ray; 1.70 A; A=100-405. +DR PDB; 7CBX; X-ray; 2.06 A; A=103-419. +DR PDBsum; 2DYL; -. +DR PDBsum; 3WZU; -. +DR PDBsum; 4UX9; -. +DR PDBsum; 5B2K; -. +DR PDBsum; 5B2L; -. +DR PDBsum; 5B2M; -. +DR PDBsum; 5Y8U; -. +DR PDBsum; 5Y90; -. +DR PDBsum; 5Z1D; -. +DR PDBsum; 5Z1E; -. +DR PDBsum; 6IB0; -. +DR PDBsum; 6IB2; -. +DR PDBsum; 6QFL; -. +DR PDBsum; 6QFR; -. +DR PDBsum; 6QFT; -. +DR PDBsum; 6QG4; -. +DR PDBsum; 6QG7; -. +DR PDBsum; 6QHO; -. +DR PDBsum; 6QHR; -. +DR PDBsum; 6YFZ; -. +DR PDBsum; 6YG0; -. +DR PDBsum; 6YG1; -. +DR PDBsum; 6YG2; -. +DR PDBsum; 6YG3; -. +DR PDBsum; 6YG4; -. +DR PDBsum; 6YG5; -. +DR PDBsum; 6YG6; -. +DR PDBsum; 6YG7; -. +DR PDBsum; 6YZ4; -. +DR PDBsum; 7CBX; -. +DR SMR; O14733; -. +DR BioGRID; 111595; 109. +DR IntAct; O14733; 39. +DR MINT; O14733; -. +DR STRING; 9606.ENSP00000381070; -. +DR BindingDB; O14733; -. +DR ChEMBL; CHEMBL3530; -. +DR DrugCentral; O14733; -. +DR GuidetoPHARMACOLOGY; 2068; -. +DR iPTMnet; O14733; -. +DR MetOSite; O14733; -. +DR PhosphoSitePlus; O14733; -. +DR BioMuta; MAP2K7; -. +DR CPTAC; CPTAC-822; -. +DR CPTAC; CPTAC-823; -. +DR EPD; O14733; -. +DR jPOST; O14733; -. +DR MassIVE; O14733; -. +DR MaxQB; O14733; -. +DR PaxDb; O14733; -. +DR PeptideAtlas; O14733; -. +DR PRIDE; O14733; -. +DR ProteomicsDB; 48192; -. [O14733-1] +DR ProteomicsDB; 48193; -. [O14733-2] +DR ProteomicsDB; 48194; -. [O14733-3] +DR ProteomicsDB; 48195; -. [O14733-4] +DR Antibodypedia; 1176; 759 antibodies from 42 providers. +DR DNASU; 5609; -. +DR Ensembl; ENST00000397979; ENSP00000381066; ENSG00000076984. +DR Ensembl; ENST00000397981; ENSP00000381068; ENSG00000076984. [O14733-4] +DR Ensembl; ENST00000397983; ENSP00000381070; ENSG00000076984. [O14733-3] +DR GeneID; 5609; -. +DR KEGG; hsa:5609; -. +DR MANE-Select; ENST00000397979.4; ENSP00000381066.3; NM_145185.4; NP_660186.1. +DR UCSC; uc002mit.4; human. [O14733-1] +DR CTD; 5609; -. +DR DisGeNET; 5609; -. +DR GeneCards; MAP2K7; -. +DR HGNC; HGNC:6847; MAP2K7. +DR HPA; ENSG00000076984; Low tissue specificity. +DR MIM; 603014; gene. +DR neXtProt; NX_O14733; -. +DR OpenTargets; ENSG00000076984; -. +DR PharmGKB; PA284; -. +DR VEuPathDB; HostDB:ENSG00000076984; -. +DR eggNOG; KOG0983; Eukaryota. +DR GeneTree; ENSGT00940000158914; -. +DR HOGENOM; CLU_000288_63_23_1; -. +DR InParanoid; O14733; -. +DR OMA; CFGYFIT; -. +DR OrthoDB; 688282at2759; -. +DR PhylomeDB; O14733; -. +DR TreeFam; TF350701; -. +DR BRENDA; 2.7.12.2; 2681. +DR PathwayCommons; O14733; -. +DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. +DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. +DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. +DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins. +DR SignaLink; O14733; -. +DR SIGNOR; O14733; -. +DR BioGRID-ORCS; 5609; 74 hits in 1082 CRISPR screens. +DR ChiTaRS; MAP2K7; human. +DR EvolutionaryTrace; O14733; -. +DR GeneWiki; MAP2K7; -. +DR GenomeRNAi; 5609; -. +DR Pharos; O14733; Tchem. +DR PRO; PR:O14733; -. +DR Proteomes; UP000005640; Chromosome 19. +DR RNAct; O14733; protein. +DR Bgee; ENSG00000076984; Expressed in testis and 239 other tissues. +DR Genevisible; O14733; HS. +DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. +DR GO; GO:0005829; C:cytosol; TAS:Reactome. +DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. +DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. +DR GO; GO:0008545; F:JUN kinase kinase activity; ISS:ARUK-UCL. +DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. +DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB. +DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IEA:Ensembl. +DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl. +DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. +DR GO; GO:0019903; F:protein phosphatase binding; ISS:BHF-UCL. +DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. +DR GO; GO:0072709; P:cellular response to sorbitol; IEA:Ensembl. +DR GO; GO:0090398; P:cellular senescence; TAS:Reactome. +DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. +DR GO; GO:0007254; P:JNK cascade; ISS:BHF-UCL. +DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central. +DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. +DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. +DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:BHF-UCL. +DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. +DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL. +DR GO; GO:1904355; P:positive regulation of telomere capping; IMP:BHF-UCL. +DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL. +DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB. +DR GO; GO:0009408; P:response to heat; IDA:UniProtKB. +DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB. +DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:UniProtKB. +DR GO; GO:0009411; P:response to UV; IDA:UniProtKB. +DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. +DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB. +DR DisProt; DP00841; -. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR008271; Ser/Thr_kinase_AS. +DR Pfam; PF00069; Pkinase; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. +PE 1: Evidence at protein level; +KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; +KW Coiled coil; Cytoplasm; Kinase; Magnesium; Metal-binding; +KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; +KW Serine/threonine-protein kinase; Stress response; Transferase; +KW Tyrosine-protein kinase. +FT INIT_MET 1 +FT /note="Removed" +FT /evidence="ECO:0007744|PubMed:19413330, +FT ECO:0007744|PubMed:22814378" +FT CHAIN 2..419 +FT /note="Dual specificity mitogen-activated protein kinase +FT kinase 7" +FT /id="PRO_0000086388" +FT DOMAIN 120..380 +FT /note="Protein kinase" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT NP_BIND 126..134 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT REGION 18..76 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 37..57 +FT /note="D domain" +FT /evidence="ECO:0000250" +FT REGION 377..400 +FT /note="DVD domain" +FT COILED 2..30 +FT /evidence="ECO:0000255" +FT COMPBIAS 18..33 +FT /note="Basic and acidic residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT ACT_SITE 243 +FT /note="Proton acceptor" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, +FT ECO:0000255|PROSITE-ProRule:PRU10027" +FT BINDING 149 +FT /note="ATP" +FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" +FT SITE 44..45 +FT /note="Cleavage; by anthrax lethal factor" +FT SITE 76..77 +FT /note="Cleavage; by anthrax lethal factor" +FT MOD_RES 2 +FT /note="N-acetylalanine" +FT /evidence="ECO:0007744|PubMed:19413330, +FT ECO:0007744|PubMed:22814378" +FT MOD_RES 271 +FT /note="Phosphoserine; by MAP3K" +FT /evidence="ECO:0000250" +FT MOD_RES 275 +FT /note="Phosphothreonine; by MAP3K" +FT /evidence="ECO:0000250" +FT MOD_RES 411 +FT /note="Phosphoserine" +FT /evidence="ECO:0007744|PubMed:23186163" +FT VAR_SEQ 42 +FT /note="T -> IIVITLSPAPAPSQRAA (in isoform 3)" +FT /evidence="ECO:0000303|PubMed:16442502" +FT /id="VSP_022309" +FT VAR_SEQ 111 +FT /note="Q -> QVPPSLWRGEGGGPARLDPSWERQWGAGGGGRAPGTLQPSLSSQ +FT (in isoform 2)" +FT /evidence="ECO:0000303|PubMed:9535930" +FT /id="VSP_004883" +FT VAR_SEQ 312 +FT /note="L -> LPCPSPSQ (in isoform 4)" +FT /evidence="ECO:0000303|PubMed:15489334" +FT /id="VSP_022310" +FT VARIANT 118 +FT /note="N -> S (in dbSNP:rs56316660)" +FT /evidence="ECO:0000269|PubMed:17344846" +FT /id="VAR_040825" +FT VARIANT 138 +FT /note="R -> C (in dbSNP:rs56106612)" +FT /evidence="ECO:0000269|PubMed:17344846" +FT /id="VAR_040826" +FT VARIANT 162 +FT /note="R -> C (in a colorectal adenocarcinoma sample; +FT somatic mutation)" +FT /evidence="ECO:0000269|PubMed:17344846" +FT /id="VAR_040827" +FT VARIANT 162 +FT /note="R -> H (in a colorectal adenocarcinoma sample; +FT somatic mutation)" +FT /evidence="ECO:0000269|PubMed:17344846" +FT /id="VAR_040828" +FT VARIANT 195 +FT /note="A -> T (in dbSNP:rs55800262)" +FT /evidence="ECO:0000269|PubMed:17344846" +FT /id="VAR_040829" +FT VARIANT 259 +FT /note="L -> F (in dbSNP:rs1053566)" +FT /evidence="ECO:0000269|PubMed:9535930" +FT /id="VAR_029890" +FT CONFLICT 94 +FT /note="Q -> H (in Ref. 2; AAB97813)" +FT /evidence="ECO:0000305" +FT CONFLICT 106 +FT /note="L -> P (in Ref. 4; ABE03013)" +FT /evidence="ECO:0000305" +FT CONFLICT 133 +FT /note="Q -> P (in Ref. 2; AAB97813)" +FT /evidence="ECO:0000305" +FT CONFLICT 142 +FT /note="T -> N (in Ref. 1; AAB88048)" +FT /evidence="ECO:0000305" +FT CONFLICT 407 +FT /note="S -> N (in Ref. 2; AAB97813)" +FT /evidence="ECO:0000305" +FT CONFLICT 415 +FT /note="L -> LG (in Ref. 2; AAB97813)" +FT /evidence="ECO:0000305" +FT STRAND 104..108 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 111..115 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 117..119 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 120..126 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 129..138 +FT /evidence="ECO:0007829|PDB:5Y90" +FT TURN 140..142 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 145..152 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 157..171 +FT /evidence="ECO:0007829|PDB:5Y90" +FT TURN 173..175 +FT /evidence="ECO:0007829|PDB:5B2L" +FT STRAND 182..187 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 189..196 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 200..202 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 203..210 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 216..237 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 246..248 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 249..251 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 257..259 +FT /evidence="ECO:0007829|PDB:5Y90" +FT TURN 262..265 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 281..283 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 286..289 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 292..297 +FT /evidence="ECO:0007829|PDB:5B2L" +FT HELIX 302..317 +FT /evidence="ECO:0007829|PDB:5Y90" +FT TURN 321..324 +FT /evidence="ECO:0007829|PDB:6IB2" +FT HELIX 328..337 +FT /evidence="ECO:0007829|PDB:5Y90" +FT STRAND 345..347 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 351..360 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 365..367 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 371..374 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 378..385 +FT /evidence="ECO:0007829|PDB:5Y90" +FT HELIX 390..401 +FT /evidence="ECO:0007829|PDB:5Y90" +SQ SEQUENCE 419 AA; 47485 MW; F1B22E050F54299A CRC64; + MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES + SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QRYQAEINDL + ENLGEMGSGT CGQVWKMRFR KTGHVIAVKQ MRRSGNKEEN KRILMDLDVV LKSHDCPYIV + QCFGTFITNT DVFIAMELMG TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI + HRDVKPSNIL LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD + IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS GDFQSFVKDC + LTKDHRKRPK YNKLLEHSFI KRYETLEVDV ASWFKDVMAK TESPRTSGVL SQPHLPFFR +// +ID Q967X2_CIOIN Unreviewed; 215 AA. +AC Q967X2; A0A1W3JIL0; +DT 01-DEC-2001, integrated into UniProtKB/TrEMBL. +DT 01-DEC-2001, sequence version 1. +DT 19-JAN-2022, entry version 106. +DE RecName: Full=Casein kinase II subunit beta {ECO:0000256|ARBA:ARBA00017775, ECO:0000256|RuleBase:RU361268}; +DE Short=CK II beta {ECO:0000256|RuleBase:RU361268}; +GN Name=CK2B {ECO:0000313|EMBL:AAK50003.1}; +GN Synonyms=Ci-casein kinase II b {ECO:0000313|EMBL:BAE06342.1}, +GN ck2b {ECO:0000313|Ensembl:ENSCINP00000008085}; +OS Ciona intestinalis (Transparent sea squirt) (Ascidia intestinalis). +OC Eukaryota; Metazoa; Chordata; Tunicata; Ascidiacea; Phlebobranchia; +OC Cionidae; Ciona. +OX NCBI_TaxID=7719 {ECO:0000313|EMBL:AAK50003.1}; +RN [1] {ECO:0000313|Proteomes:UP000008144} +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RX PubMed=12481130; DOI=10.1126/science.1080049; +RA Dehal P., Satou Y., Campbell R.K., Chapman J., Degnan B., De Tomaso A., +RA Davidson B., Di Gregorio A., Gelpke M., Goodstein D.M., Harafuji N., +RA Hastings K.E., Ho I., Hotta K., Huang W., Kawashima T., Lemaire P., +RA Martinez D., Meinertzhagen I.A., Necula S., Nonaka M., Putnam N., Rash S., +RA Saiga H., Satake M., Terry A., Yamada L., Wang H.G., Awazu S., Azumi K., +RA Boore J., Branno M., Chin-Bow S., DeSantis R., Doyle S., Francino P., +RA Keys D.N., Haga S., Hayashi H., Hino K., Imai K.S., Inaba K., Kano S., +RA Kobayashi K., Kobayashi M., Lee B.I., Makabe K.W., Manohar C., Matassi G., +RA Medina M., Mochizuki Y., Mount S., Morishita T., Miura S., Nakayama A., +RA Nishizaka S., Nomoto H., Ohta F., Oishi K., Rigoutsos I., Sano M., +RA Sasaki A., Sasakura Y., Shoguchi E., Shin-i T., Spagnuolo A., Stainier D., +RA Suzuki M.M., Tassy O., Takatori N., Tokuoka M., Yagi K., Yoshizaki F., +RA Wada S., Zhang C., Hyatt P.D., Larimer F., Detter C., Doggett N., +RA Glavina T., Hawkins T., Richardson P., Lucas S., Kohara Y., Levine M., +RA Satoh N., Rokhsar D.S.; +RT "The draft genome of Ciona intestinalis: insights into chordate and +RT vertebrate origins."; +RL Science 298:2157-2167(2002). +RN [2] {ECO:0000313|EMBL:BAE06342.1} +RP NUCLEOTIDE SEQUENCE. +RX PubMed=12736827; DOI=10.1007/s00427-003-0330-z; +RA Satou Y., Satoh N.; +RT "Genomewide surveys of developmentally relevant genes in Ciona +RT intestinalis."; +RL Dev. Genes Evol. 213:211-212(2003). +RN [3] {ECO:0000313|EMBL:BAE06342.1} +RP NUCLEOTIDE SEQUENCE. +RX PubMed=15269171; DOI=10.1242/dev.01270; +RA Imai K.S., Hino K., Yagi K., Satoh N., Satou Y.; +RT "Gene expression profiles of transcription factors and signaling molecules +RT in the ascidian embryo: towards a comprehensive understanding of gene +RT networks."; +RL Development 131:4047-4058(2004). +RN [4] {ECO:0000313|EMBL:AAK50003.1} +RP NUCLEOTIDE SEQUENCE. +RX PubMed=15159401; DOI=10.1074/jbc.M401085200; +RA Russo G.L., Tosto M., Mupo A., Castellano I., Cuomo A., Tosti E.; +RT "Biochemical and functional characterization of protein kinase CK2 in +RT ascidian Ciona intestinalis oocytes at fertilization. Cloning and sequence +RT analysis of cDNA for alpha and beta subunits."; +RL J. Biol. Chem. 279:33012-33023(2004). +RN [5] {ECO:0000313|EMBL:BAE06342.1} +RP NUCLEOTIDE SEQUENCE. +RA Satou Y.; +RT "Expressed genes in Ciona intestinalis."; +RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. +RN [6] {ECO:0000313|Ensembl:ENSCINP00000008085} +RP IDENTIFICATION. +RG Ensembl; +RL Submitted (FEB-2012) to UniProtKB. +CC -!- FUNCTION: Regulatory subunit of casein kinase II/CK2. As part of the +CC kinase complex regulates the basal catalytic activity of the alpha +CC subunit a constitutively active serine/threonine-protein kinase that +CC phosphorylates a large number of substrates containing acidic residues +CC C-terminal to the phosphorylated serine or threonine. Participates in +CC Wnt signaling. {ECO:0000256|RuleBase:RU361268}. +CC -!- SUBUNIT: Tetramer of two alpha and two beta subunits. +CC {ECO:0000256|RuleBase:RU361268}. +CC -!- SIMILARITY: Belongs to the casein kinase 2 subunit beta family. +CC {ECO:0000256|ARBA:ARBA00006941, ECO:0000256|RuleBase:RU361268}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; EAAA01000113; -; NOT_ANNOTATED_CDS; Genomic_DNA. +DR EMBL; AF360544; AAK50003.1; -; mRNA. +DR EMBL; AB210337; BAE06342.1; -; mRNA. +DR RefSeq; NP_001027591.1; NM_001032419.1. +DR RefSeq; XP_009862100.1; XM_009863798.2. +DR STRING; 7719.XP_009862100.1; -. +DR Ensembl; ENSCINT00000008085; ENSCINP00000008085; ENSCING00000003902. +DR GeneID; 445589; -. +DR KEGG; cin:445589; -. +DR CTD; 692538; -. +DR GeneTree; ENSGT00390000003781; -. +DR HOGENOM; CLU_034027_3_3_1; -. +DR OMA; LCQSQPL; -. +DR OrthoDB; 1335521at2759; -. +DR TreeFam; TF314462; -. +DR Proteomes; UP000008144; Unassembled WGS sequence. +DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. +DR GO; GO:0005956; C:protein kinase CK2 complex; IBA:GO_Central. +DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0019887; F:protein kinase regulator activity; IBA:GO_Central. +DR GO; GO:0080163; P:regulation of protein serine/threonine phosphatase activity; IBA:GO_Central. +DR Gene3D; 1.10.1820.10; -; 1. +DR InterPro; IPR016149; Casein_kin_II_reg-sub_N. +DR InterPro; IPR035991; Casein_kinase_II_beta-like. +DR InterPro; IPR000704; Casein_kinase_II_reg-sub. +DR PANTHER; PTHR11740; PTHR11740; 1. +DR Pfam; PF01214; CK_II_beta; 1. +DR PRINTS; PR00472; CASNKINASEII. +DR SMART; SM01085; CK_II_beta; 1. +DR SUPFAM; SSF57798; SSF57798; 1. +PE 2: Evidence at transcript level; +KW Kinase {ECO:0000313|EMBL:AAK50003.1}; +KW Reference proteome {ECO:0000313|Proteomes:UP000008144}; +KW Transferase {ECO:0000313|EMBL:AAK50003.1}. +SQ SEQUENCE 215 AA; 24938 MW; 62A43DCB6C6CEF3F CRC64; + MSSSEEVSWI SWFCGLRGNE FFCEVDEDYI QDKFNLTGLG EQVPHYRQAL DMILDLEPDD + DLEDNTNQSD LIEQAAEMLY GLIHARYTLT NRGIAQMLEK YQQGDFGHCS RVYCENQPML + PIGLSDVPGE AMVKLYCPKC QDVYTPKSSR HHHTDGAYFG TGFPHMLFMV HPEYRPKRPT + NQFVSRLFGF KIHPMAYQLQ YQASQKLKNP SKLRH +// +ID A7RQU9_NEMVE Unreviewed; 376 AA. +AC A7RQU9; +DT 02-OCT-2007, integrated into UniProtKB/TrEMBL. +DT 02-OCT-2007, sequence version 1. +DT 19-JAN-2022, entry version 86. +DE SubName: Full=Cytoplasmic creatine kinase protein {ECO:0000313|EMBL:BAL73226.1}; +DE SubName: Full=Predicted protein {ECO:0000313|EMBL:EDO46231.1}; +GN Name=cytoplasmic creatine kinase {ECO:0000313|EMBL:BAL73226.1}; +GN ORFNames=v1g234345 {ECO:0000313|EMBL:EDO46231.1}; +OS Nematostella vectensis (Starlet sea anemone). +OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria; +OC Edwardsiidae; Nematostella. +OX NCBI_TaxID=45351 {ECO:0000313|Proteomes:UP000001593}; +RN [1] {ECO:0000313|EMBL:EDO46231.1, ECO:0000313|Proteomes:UP000001593} +RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. +RC STRAIN=CH2 X CH6 {ECO:0000313|Proteomes:UP000001593}; +RX PubMed=17615350; DOI=10.1126/science.1139158; +RA Putnam N.H., Srivastava M., Hellsten U., Dirks B., Chapman J., Salamov A., +RA Terry A., Shapiro H., Lindquist E., Kapitonov V.V., Jurka J., +RA Genikhovich G., Grigoriev I.V., Lucas S.M., Steele R.E., Finnerty J.R., +RA Technau U., Martindale M.Q., Rokhsar D.S.; +RT "Sea anemone genome reveals ancestral eumetazoan gene repertoire and +RT genomic organization."; +RL Science 317:86-94(2007). +RN [2] {ECO:0000313|EMBL:BAL73226.1} +RP NUCLEOTIDE SEQUENCE. +RX PubMed=22305986; DOI=10.1016/j.gene.2012.01.036; +RA Uda K., Ellington W.R., Suzuki T.; +RT "A diverse array of creatine kinase and arginine kinase isoform genes is +RT present in the starlet sea anemone Nematostella vectensis, a cnidarian +RT model system for studying developmental evolution."; +RL Gene 497:214-227(2012). +CC -!- SIMILARITY: Belongs to the ATP:guanido phosphotransferase family. +CC {ECO:0000256|ARBA:ARBA00006798, ECO:0000256|PROSITE-ProRule:PRU00842, +CC ECO:0000256|RuleBase:RU000505}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AB665525; BAL73226.1; -; mRNA. +DR EMBL; DS469529; EDO46231.1; -; Genomic_DNA. +DR RefSeq; XP_001638294.1; XM_001638244.1. +DR STRING; 45351.EDO46231; -. +DR EnsemblMetazoa; EDO46231; EDO46231; NEMVEDRAFT_v1g234345. +DR GeneID; 5518278; -. +DR KEGG; nve:5518278; -. +DR eggNOG; KOG3581; Eukaryota. +DR HOGENOM; CLU_019868_4_2_1; -. +DR OMA; RAVENMS; -. +DR OrthoDB; 825025at2759; -. +DR Proteomes; UP000001593; Unassembled WGS sequence. +DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. +DR GO; GO:0004111; F:creatine kinase activity; IBA:GO_Central. +DR GO; GO:0016301; F:kinase activity; IBA:GO_Central. +DR GO; GO:0046314; P:phosphocreatine biosynthetic process; IBA:GO_Central. +DR Gene3D; 1.10.135.10; -; 1. +DR InterPro; IPR000749; ATP-guanido_PTrfase. +DR InterPro; IPR022415; ATP-guanido_PTrfase_AS. +DR InterPro; IPR022414; ATP-guanido_PTrfase_cat. +DR InterPro; IPR022413; ATP-guanido_PTrfase_N. +DR InterPro; IPR036802; ATP-guanido_PTrfase_N_sf. +DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom. +DR PANTHER; PTHR11547; PTHR11547; 2. +DR Pfam; PF00217; ATP-gua_Ptrans; 1. +DR Pfam; PF02807; ATP-gua_PtransN; 1. +DR SUPFAM; SSF48034; SSF48034; 1. +DR SUPFAM; SSF55931; SSF55931; 1. +DR PROSITE; PS00112; PHOSPHAGEN_KINASE; 1. +DR PROSITE; PS51510; PHOSPHAGEN_KINASE_C; 1. +DR PROSITE; PS51509; PHOSPHAGEN_KINASE_N; 1. +PE 2: Evidence at transcript level; +KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE- +KW ProRule:PRU00843}; +KW Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|PROSITE- +KW ProRule:PRU00843}; +KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE- +KW ProRule:PRU00843}; Reference proteome {ECO:0000313|Proteomes:UP000001593}; +KW Transferase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|PROSITE- +KW ProRule:PRU00843}. +FT DOMAIN 9..95 +FT /note="Phosphagen kinase N-terminal" +FT /evidence="ECO:0000259|PROSITE:PS51509" +FT DOMAIN 121..364 +FT /note="Phosphagen kinase C-terminal" +FT /evidence="ECO:0000259|PROSITE:PS51510" +FT NP_BIND 124..128 +FT /note="ATP" +FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00843" +FT NP_BIND 288..292 +FT /note="ATP" +FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00843" +FT NP_BIND 317..322 +FT /note="ATP" +FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00843" +FT BINDING 187 +FT /note="ATP" +FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00843" +FT BINDING 232 +FT /note="ATP" +FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00843" +SQ SEQUENCE 376 AA; 42117 MW; D5933E6281037882 CRC64; + MTSVKSAYKQ FSADDDFPDL SQHNNYMAKV LTKEIYRSLR DKSTKNGFTL DDIIQTGVDN + PGHPFIMTVG CVAGDEESYD VFAELLDPVI ELRHGGYKKT DKHKTDLNPD NLKGGALDPK + YVLSSRVRTG RSIRGFCLPP HCSRAERRSV EKISVDALAK LDGEFKGKYY PLNKMTDEEQ + EQLINDHFLF DKPVSPLLTC AGMARDWPDA RGIWHNENKN FLVWVNEEDH TRVISMEKGG + DMRAVFTRFC NGLNKVESLI KEAGYEFMWN EHLGYVLTCP SNLGTGLRAG VHLKIPLLSQ + DEKRLDAILA KLKLQKRGTG GVDTASVGGV YDISNADRIG FSEVELVQGM VDGVGLLIEM + EKRLEEGKAI DDLIPK +// +ID Q9NA00_9CRUS Unreviewed; 494 AA. +AC Q9NA00; +DT 01-OCT-2000, integrated into UniProtKB/TrEMBL. +DT 01-OCT-2000, sequence version 1. +DT 19-JAN-2022, entry version 89. +DE RecName: Full=Non-specific protein-tyrosine kinase {ECO:0000256|ARBA:ARBA00011903}; +DE EC=2.7.10.2 {ECO:0000256|ARBA:ARBA00011903}; +DE Flags: Fragment; +GN Name=wee1-like CDK tyrosine kinase {ECO:0000313|EMBL:CAB99477.1}; +OS Daphnia magna. +OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Crustacea; Branchiopoda; +OC Diplostraca; Cladocera; Anomopoda; Daphniidae; Daphnia. +OX NCBI_TaxID=35525 {ECO:0000313|EMBL:CAB99477.1}; +RN [1] {ECO:0000313|EMBL:CAB99477.1} +RP NUCLEOTIDE SEQUENCE. +RA Richards J.R., Cryer J., Kille P.; +RT "Isolation of genes from Daphnia magna."; +RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. +CC -!- COFACTOR: +CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; +CC Evidence={ECO:0000256|PIRSR:PIRSR037281-3}; +CC Note=Binds 2 magnesium ions per subunit. +CC {ECO:0000256|PIRSR:PIRSR037281-3}; +CC -!- SIMILARITY: Belongs to the protein kinase superfamily. +CC {ECO:0000256|RuleBase:RU000304}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AJ292557; CAB99477.1; -; mRNA. +DR GO; GO:0005634; C:nucleus; IEA:InterPro. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. +DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. +DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:InterPro. +DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0000278; P:mitotic cell cycle; IEA:InterPro. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR017441; Protein_kinase_ATP_BS. +DR InterPro; IPR008271; Ser/Thr_kinase_AS. +DR InterPro; IPR017164; Wee1-like_protein_kinase. +DR Pfam; PF00069; Pkinase; 1. +DR PIRSF; PIRSF037281; Wee1-like_protein_kinase; 1. +DR SMART; SM00220; S_TKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. +PE 2: Evidence at transcript level; +KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRSR:PIRSR037281- +KW 2}; Kinase {ECO:0000256|RuleBase:RU000304}; +KW Magnesium {ECO:0000256|PIRSR:PIRSR037281-3}; +KW Metal-binding {ECO:0000256|PIRSR:PIRSR037281-3}; +KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022840, +KW ECO:0000256|PIRSR:PIRSR037281-2}; +KW Serine/threonine-protein kinase {ECO:0000256|RuleBase:RU000304}; +KW Transferase {ECO:0000256|RuleBase:RU000304}. +FT DOMAIN 212..486 +FT /note="Protein kinase" +FT /evidence="ECO:0000259|PROSITE:PS50011" +FT NP_BIND 218..226 +FT /note="ATP" +FT /evidence="ECO:0000256|PIRSR:PIRSR037281-2" +FT REGION 23..82 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 129..154 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT COMPBIAS 33..50 +FT /note="Polar residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT ACT_SITE 339 +FT /note="Proton acceptor" +FT /evidence="ECO:0000256|PIRSR:PIRSR037281-1" +FT METAL 344 +FT /note="Magnesium; via carbonyl oxygen" +FT /evidence="ECO:0000256|PIRSR:PIRSR037281-3" +FT METAL 381 +FT /note="Magnesium; via carbonyl oxygen" +FT /evidence="ECO:0000256|PIRSR:PIRSR037281-3" +FT BINDING 241 +FT /note="ATP" +FT /evidence="ECO:0000256|PIRSR:PIRSR037281-2" +FT BINDING 242 +FT /note="ATP" +FT /evidence="ECO:0000256|PROSITE-ProRule:PRU10141" +FT NON_TER 494 +FT /evidence="ECO:0000313|EMBL:CAB99477.1" +SQ SEQUENCE 494 AA; 55301 MW; BC10BC034E593178 CRC64; + MDRDIEMEEN HCRIAQRLEF PLSDEEDLHE ASTGNNRTSS NSSSDRLDSS GSDEGLGMTI + RITSPRKPRF IRSRAREPMS PPYSGVRALR LFDSPATPKT LLENSSAIMT PVLATPAPRN + RMRTLFTMSS TKSSDKKDNM NTPPAANVNP FTPTGMLLTS KKRTRSKRSL NGSLVNSFDE + EVHEATDESD EEMPPKRIAL HQTSVPRYHK EFHEICLIGK GEFGSVHKCL NRLDGCTYAV + KKSLMPVAGS PNERSALNEV WAHAVLGQHP HAVRYYSAWA ENGHMIIQNE FCNSGTLEEL + IRTNQLNNVT VNEPQLKSTL LQIAEGLHYI HSKQLAHMDI KPGNIFICRE NSDDCSVHHD + SDDGFDELDD DYGSVTYKIG DLGHVTSVVQ PIVEEGDCRY LPVEILRENY EHLTKADIFS + LGLTIYEMAG GGQLPKNGDE WHAIRQGRLP YNGRYSIELH NLLELMIHPD PTLRPSTQVL + TQHPVLGPNG AKSK +// +ID Q91356_COTCO Unreviewed; 367 AA. +AC Q91356; +DT 01-NOV-1996, integrated into UniProtKB/TrEMBL. +DT 01-NOV-1996, sequence version 1. +DT 02-JUN-2021, entry version 95. +DE RecName: Full=Vascular endothelial growth factor receptor 3 {ECO:0000256|ARBA:ARBA00022258}; +DE Flags: Fragment; +GN Name=endothelial kinase Quek2 {ECO:0000313|EMBL:AAB28128.1}; +OS Coturnix coturnix (Common quail) (Tetrao coturnix). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; +OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; +OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; +OC Perdicinae; Coturnix. +OX NCBI_TaxID=9091 {ECO:0000313|EMBL:AAB28128.1}; +RN [1] {ECO:0000313|EMBL:AAB28128.1} +RP NUCLEOTIDE SEQUENCE. +RX PubMed=8396413; DOI=10.1016/0925-4773(93)90096-G; +RA Eichmann A., Marcelle C., Breant C., Le Douarin N.M.; +RT "Two molecules related to the VEGF receptor are expressed in early +RT endothelial cells during avian embryonic development."; +RL Mech. Dev. 42:33-48(1993). +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; S65207; AAB28128.1; -; mRNA. +DR PIR; B56598; B56598. +DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro. +DR GO; GO:0005524; F:ATP binding; IEA:InterPro. +DR GO; GO:0005021; F:vascular endothelial growth factor-activated receptor activity; IEA:InterPro. +DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IEA:InterPro. +DR InterPro; IPR011009; Kinase-like_dom_sf. +DR InterPro; IPR000719; Prot_kinase_dom. +DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. +DR InterPro; IPR008266; Tyr_kinase_AS. +DR InterPro; IPR020635; Tyr_kinase_cat_dom. +DR InterPro; IPR009137; VEGFR3_rcpt. +DR PANTHER; PTHR24416:SF562; PTHR24416:SF562; 1. +DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. +DR PRINTS; PR00109; TYRKINASE. +DR SMART; SM00219; TyrKc; 1. +DR SUPFAM; SSF56112; SSF56112; 1. +DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. +DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. +PE 2: Evidence at transcript level; +KW Kinase {ECO:0000313|EMBL:AAB28128.1}; +KW Transferase {ECO:0000313|EMBL:AAB28128.1}. +FT DOMAIN 1..173 +FT /note="Protein kinase" +FT /evidence="ECO:0000259|PROSITE:PS50011" +FT REGION 184..212 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT REGION 287..367 +FT /note="Disordered" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT COMPBIAS 184..209 +FT /note="Polar residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT COMPBIAS 321..335 +FT /note="Polar residues" +FT /evidence="ECO:0000256|SAM:MobiDB-lite" +FT NON_TER 367 +FT /evidence="ECO:0000313|EMBL:AAB28128.1" +SQ SEQUENCE 367 AA; 41793 MW; 04442B35940027A0 CRC64; + WMDLWQSPLT MEDLICYSFQ VARGMEFLAS RKCIHRDLAA RNILLSENNV VKICDFGLAR + DIYKDPDYVR KGSARLPLKW MAPESIFDKV YTTQSDVWSL GVLLWEIFSL GASPYPGVQI + NEEFCQRFKD GTRMRAPEYT TAEIYRIMLS CWHGDPKERP TFSDLVEILG NLLQENVQQE + GKDYIPLNDS HSSEDDGFSQ VPSSAQQNSD EEDFDMRIRC HSLAARYYNC VSFPGCLTGG + NQIRCSSRIK TFEEFPMTHT MYKAHPDNQT DSGMVLASEE FERIENRHRK EGGFSSKGPN + RTAELSAEQS DLRGRCRPSY GSQVGGQTFY NSEYGELSEH SEDRSCTPPA EGASPPALHA + SFFSEQY +// +ID Q9PU23_TRASE Unreviewed; 216 AA. +AC Q9PU23; +DT 01-MAY-2000, integrated into UniProtKB/TrEMBL. +DT 01-MAY-2000, sequence version 1. +DT 29-SEP-2021, entry version 82. +DE RecName: Full=Pyruvate kinase {ECO:0000256|ARBA:ARBA00012142, ECO:0000256|RuleBase:RU000504}; +DE EC=2.7.1.40 {ECO:0000256|ARBA:ARBA00012142, ECO:0000256|RuleBase:RU000504}; +DE Flags: Fragment; +GN Name=pyruvate kinase {ECO:0000313|EMBL:CAB61266.1}; +OS Trachemys scripta elegans (Red-eared slider turtle). +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; +OC Archelosauria; Testudinata; Testudines; Cryptodira; Durocryptodira; +OC Testudinoidea; Emydidae; Trachemys. +OX NCBI_TaxID=31138 {ECO:0000313|EMBL:CAB61266.1}; +RN [1] {ECO:0000313|EMBL:CAB61266.1} +RP NUCLEOTIDE SEQUENCE. +RC TISSUE=Liver {ECO:0000313|EMBL:CAB61266.1}; +RX PubMed=10555283; +RA Hughes S., Zelus D., Mouchiroud D.; +RT "Warm-blooded isochore structure in Nile crocodile and turtle."; +RL Mol. Biol. Evol. 16:1521-1527(1999). +RN [2] {ECO:0000313|EMBL:CAB61266.1} +RP NUCLEOTIDE SEQUENCE. +RC TISSUE=Liver {ECO:0000313|EMBL:CAB61266.1}; +RA Hughes S.N.; +RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + pyruvate = ADP + H(+) + phosphoenolpyruvate; +CC Xref=Rhea:RHEA:18157, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58702, ChEBI:CHEBI:456216; +CC EC=2.7.1.40; Evidence={ECO:0000256|ARBA:ARBA00001174, +CC ECO:0000256|RuleBase:RU000504}; +CC -!- COFACTOR: +CC Name=K(+); Xref=ChEBI:CHEBI:29103; +CC Evidence={ECO:0000256|ARBA:ARBA00001958}; +CC -!- COFACTOR: +CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; +CC Evidence={ECO:0000256|ARBA:ARBA00001946}; +CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- +CC glyceraldehyde 3-phosphate: step 5/5. {ECO:0000256|ARBA:ARBA00004997, +CC ECO:0000256|RuleBase:RU000504}. +CC -!- SIMILARITY: Belongs to the pyruvate kinase family. +CC {ECO:0000256|ARBA:ARBA00008663, ECO:0000256|RuleBase:RU000504}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AJ243136; CAB61266.1; -; mRNA. +DR UniPathway; UPA00109; UER00188. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. +DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. +DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro. +DR GO; GO:0004743; F:pyruvate kinase activity; IEA:UniProtKB-EC. +DR Gene3D; 3.20.20.60; -; 1. +DR InterPro; IPR001697; Pyr_Knase. +DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom. +DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf. +DR InterPro; IPR011037; Pyrv_Knase-like_insert_dom_sf. +DR InterPro; IPR015793; Pyrv_Knase_brl. +DR PANTHER; PTHR11817; PTHR11817; 1. +DR Pfam; PF00224; PK; 1. +DR PRINTS; PR01050; PYRUVTKNASE. +DR SUPFAM; SSF50800; SSF50800; 1. +DR SUPFAM; SSF51621; SSF51621; 1. +DR TIGRFAMs; TIGR01064; pyruv_kin; 1. +PE 2: Evidence at transcript level; +KW ATP-binding {ECO:0000256|ARBA:ARBA00022840}; +KW Glycolysis {ECO:0000256|ARBA:ARBA00023152, ECO:0000256|RuleBase:RU000504}; +KW Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|RuleBase:RU000504}; +KW Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|RuleBase:RU000504}; +KW Metal-binding {ECO:0000256|ARBA:ARBA00022723}; +KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022840}; +KW Pyruvate {ECO:0000256|ARBA:ARBA00023317, ECO:0000313|EMBL:CAB61266.1}; +KW Transferase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|RuleBase:RU000504}. +FT DOMAIN 4..216 +FT /note="PK" +FT /evidence="ECO:0000259|Pfam:PF00224" +FT NON_TER 1 +FT /evidence="ECO:0000313|EMBL:CAB61266.1" +FT NON_TER 216 +FT /evidence="ECO:0000313|EMBL:CAB61266.1" +SQ SEQUENCE 216 AA; 23513 MW; 7E8F42877545B562 CRC64; + KGSGTAEVEL KKGATLKVTL DNAFMEKCDE NVLWLDYKNL PNVVDVGSKI YIDDGLISLQ + VKGKGADYVL TEVENGGMLG SKKGVNLPGA AVDLPAVSEK DIQDLKFGVE QDVDMVFASF + IRKAADVHAV RQVLGEKGKX IKIISEIENH EGVRRFDEVL EASDGIMVAR GDLGIEIPAE + KVFLAQKMMI GRCNRAGKPI ICATQMLESM IKKPRP +// +ID Q90WS6_9SAUR Unreviewed; 215 AA. +AC Q90WS6; +DT 01-DEC-2001, integrated into UniProtKB/TrEMBL. +DT 01-DEC-2001, sequence version 1. +DT 29-SEP-2021, entry version 81. +DE RecName: Full=Pyruvate kinase {ECO:0000256|ARBA:ARBA00012142, ECO:0000256|RuleBase:RU000504}; +DE EC=2.7.1.40 {ECO:0000256|ARBA:ARBA00012142, ECO:0000256|RuleBase:RU000504}; +DE Flags: Fragment; +GN Name=pyruvate kinase {ECO:0000313|EMBL:CAC69539.1}; +OS Elaphe sp. +OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; +OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; +OC Serpentes; Colubroidea; Colubridae; Colubrinae; Elaphe; +OC unclassified Elaphe. +OX NCBI_TaxID=114965 {ECO:0000313|EMBL:CAC69539.1}; +RN [1] {ECO:0000313|EMBL:CAC69539.1} +RP NUCLEOTIDE SEQUENCE. +RC TISSUE=Liver {ECO:0000313|EMBL:CAC69539.1}; +RA Hughes S.N.; +RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. +RN [2] {ECO:0000313|EMBL:CAC69539.1} +RP NUCLEOTIDE SEQUENCE. +RC TISSUE=Liver {ECO:0000313|EMBL:CAC69539.1}; +RA Hughes S., Laurin M., Gouy M., Mouchiroud D.; +RT "The phylogenetic position of turtles among sauropsidae remains contentious +RT with new nuclear data."; +RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. +CC -!- CATALYTIC ACTIVITY: +CC Reaction=ATP + pyruvate = ADP + H(+) + phosphoenolpyruvate; +CC Xref=Rhea:RHEA:18157, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, +CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58702, ChEBI:CHEBI:456216; +CC EC=2.7.1.40; Evidence={ECO:0000256|ARBA:ARBA00001174, +CC ECO:0000256|RuleBase:RU000504}; +CC -!- COFACTOR: +CC Name=K(+); Xref=ChEBI:CHEBI:29103; +CC Evidence={ECO:0000256|ARBA:ARBA00001958}; +CC -!- COFACTOR: +CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; +CC Evidence={ECO:0000256|ARBA:ARBA00001946}; +CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- +CC glyceraldehyde 3-phosphate: step 5/5. {ECO:0000256|ARBA:ARBA00004997, +CC ECO:0000256|RuleBase:RU000504}. +CC -!- SIMILARITY: Belongs to the pyruvate kinase family. +CC {ECO:0000256|ARBA:ARBA00008663, ECO:0000256|RuleBase:RU000504}. +CC --------------------------------------------------------------------------- +CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms +CC Distributed under the Creative Commons Attribution (CC BY 4.0) License +CC --------------------------------------------------------------------------- +DR EMBL; AJ286864; CAC69539.1; -; mRNA. +DR UniPathway; UPA00109; UER00188. +DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. +DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. +DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. +DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro. +DR GO; GO:0004743; F:pyruvate kinase activity; IEA:UniProtKB-EC. +DR Gene3D; 3.20.20.60; -; 1. +DR InterPro; IPR001697; Pyr_Knase. +DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom. +DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf. +DR InterPro; IPR011037; Pyrv_Knase-like_insert_dom_sf. +DR InterPro; IPR018209; Pyrv_Knase_AS. +DR InterPro; IPR015793; Pyrv_Knase_brl. +DR PANTHER; PTHR11817; PTHR11817; 1. +DR Pfam; PF00224; PK; 1. +DR PRINTS; PR01050; PYRUVTKNASE. +DR SUPFAM; SSF50800; SSF50800; 1. +DR SUPFAM; SSF51621; SSF51621; 1. +DR PROSITE; PS00110; PYRUVATE_KINASE; 1. +PE 2: Evidence at transcript level; +KW ATP-binding {ECO:0000256|ARBA:ARBA00022840}; +KW Glycolysis {ECO:0000256|ARBA:ARBA00023152, ECO:0000256|RuleBase:RU000504}; +KW Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|RuleBase:RU000504}; +KW Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|RuleBase:RU000504}; +KW Metal-binding {ECO:0000256|ARBA:ARBA00022723}; +KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022840}; +KW Pyruvate {ECO:0000256|ARBA:ARBA00023317, ECO:0000313|EMBL:CAC69539.1}; +KW Transferase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|RuleBase:RU000504}. +FT DOMAIN 4..214 +FT /note="PK" +FT /evidence="ECO:0000259|Pfam:PF00224" +FT NON_TER 1 +FT /evidence="ECO:0000313|EMBL:CAC69539.1" +FT NON_TER 215 +FT /evidence="ECO:0000313|EMBL:CAC69539.1" +SQ SEQUENCE 215 AA; 23520 MW; 50FED93ADFDA0C15 CRC64; + KGSGTAEVEL KKGATLKVTL DNAYMEKCDE HVLWVDYKNI IKVVEIGSKI YVDDGLISLK + VKEKGADFIM TEIENGGLLG SKKGVNLPGA AVDLPAVPEK DIQDLKFGVE QDVDMVLASF + IRKAADVHAV RKVLGEKGKN IKIISKIENH EGVRRFDEIM EASDGIMVAR GDLGIEIPAE + KVFLAQKMMI GRCNRAGKPI ICATQMLESM IKKPP +//