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Database: UniProt/SWISS-PROT UniProt/TrEMBL
Entry: MK04_HUMAN B4DEW2_HUMAN K7ELV1_HUMAN
LinkDB: MK04_HUMAN B4DEW2_HUMAN K7ELV1_HUMAN
Original site: MK04_HUMAN B4DEW2_HUMAN K7ELV1_HUMAN 
ID   MK04_HUMAN              Reviewed;         587 AA.
AC   P31152; A1A4C4; Q0VG04;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   25-NOV-2008, sequence version 2.
DT   27-MAR-2024, entry version 200.
DE   RecName: Full=Mitogen-activated protein kinase 4;
DE            Short=MAP kinase 4;
DE            Short=MAPK 4;
DE            EC=2.7.11.24;
DE   AltName: Full=Extracellular signal-regulated kinase 4;
DE            Short=ERK-4;
DE   AltName: Full=MAP kinase isoform p63;
DE            Short=p63-MAPK;
GN   Name=MAPK4; Synonyms=ERK4, PRKM4;
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].
RX   PubMed=1319925; DOI=10.1016/0014-5793(92)80612-k;
RA   Gonzalez F.A., Raden D.L., Rigby M.R., Davis R.J.;
RT   "Heterogeneous expression of four MAP kinase isoforms in human tissues.";
RL   FEBS Lett. 304:170-178(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16177791; DOI=10.1038/nature03983;
RA   Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA   Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA   Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA   Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA   Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA   Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA   Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA   Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 18.";
RL   Nature 437:551-555(2005).
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-38.
RC   TISSUE=Brain, and Cerebellum;
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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, 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   [7]
RP   PHOSPHORYLATION AT SER-186.
RX   PubMed=21177870; DOI=10.1074/jbc.m110.181529;
RA   Deleris P., Trost M., Topisirovic I., Tanguay P.L., Borden K.L.,
RA   Thibault P., Meloche S.;
RT   "Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated
RT   kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5
RT   signaling pathway.";
RL   J. Biol. Chem. 286:6470-6478(2011).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
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   [9]
RP   VARIANTS [LARGE SCALE ANALYSIS] MET-38 AND PRO-371.
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: Atypical MAPK protein. Phosphorylates microtubule-associated
CC       protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed
CC       with MAPKAPK5 is still unclear, but the complex follows a complex set
CC       of phosphorylation events: upon interaction with atypical MAPKAPK5,
CC       ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates
CC       phosphorylation and activation of MAPKAPK5, which in turn
CC       phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By
CC       similarity). {ECO:0000250}.
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=2.7.11.24;
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=2.7.11.24;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC   -!- ACTIVITY REGULATION: Activated by phosphorylation at Ser-186.
CC   -!- SUBUNIT: Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via
CC       FRIEDE motif) MAPKAPK5 (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       P31152; P08238: HSP90AB1; NbExp=3; IntAct=EBI-3906061, EBI-352572;
CC       P31152; P62258: YWHAE; NbExp=2; IntAct=EBI-3906061, EBI-356498;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC       Note=Translocates to the cytoplasm following interaction with MAPKAPK5.
CC       {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: High expression in heart and brain.
CC   -!- DOMAIN: The FRIEDE motif is required for docking MAPKAPK5.
CC       {ECO:0000250}.
CC   -!- DOMAIN: In contrast to classical MAPKs, the TXY motif within the
CC       activation loop is replaced by the SEG motif, whose phosphorylation
CC       activates the MAP kinases.
CC   -!- PTM: Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in
CC       catalytic activation. Phosphorylated by MAPKAPK5 at other sites.
CC       {ECO:0000269|PubMed:21177870}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC       protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA42411.1; Type=Frameshift; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/41293/MAPK4";
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DR   EMBL; X59727; CAA42411.1; ALT_FRAME; mRNA.
DR   EMBL; AK295058; BAG58107.1; -; mRNA.
DR   EMBL; AC012433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471096; EAW62976.1; -; Genomic_DNA.
DR   EMBL; CH471096; EAW62977.1; -; Genomic_DNA.
DR   EMBL; BC050299; AAH50299.1; -; mRNA.
DR   EMBL; BC117216; AAI17217.1; -; mRNA.
DR   CCDS; CCDS42437.1; -.
DR   PIR; S23429; S23429.
DR   RefSeq; NP_001278968.1; NM_001292039.1.
DR   RefSeq; NP_001278969.1; NM_001292040.1.
DR   RefSeq; NP_002738.2; NM_002747.3.
DR   RefSeq; XP_005258356.1; XM_005258299.3.
DR   RefSeq; XP_011524376.1; XM_011526074.2.
DR   RefSeq; XP_011524377.1; XM_011526075.2.
DR   RefSeq; XP_011524378.1; XM_011526076.2.
DR   RefSeq; XP_016881328.1; XM_017025839.1.
DR   AlphaFoldDB; P31152; -.
DR   SMR; P31152; -.
DR   BioGRID; 111582; 71.
DR   IntAct; P31152; 47.
DR   STRING; 9606.ENSP00000383234; -.
DR   BindingDB; P31152; -.
DR   ChEMBL; CHEMBL5759; -.
DR   DrugBank; DB00945; Acetylsalicylic acid.
DR   DrugBank; DB02587; Colforsin.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB01017; Minocycline.
DR   DrugCentral; P31152; -.
DR   iPTMnet; P31152; -.
DR   PhosphoSitePlus; P31152; -.
DR   SwissPalm; P31152; -.
DR   BioMuta; MAPK4; -.
DR   DMDM; 215274102; -.
DR   CPTAC; CPTAC-883; -.
DR   CPTAC; CPTAC-884; -.
DR   EPD; P31152; -.
DR   jPOST; P31152; -.
DR   MassIVE; P31152; -.
DR   PaxDb; 9606-ENSP00000383234; -.
DR   PeptideAtlas; P31152; -.
DR   ProteomicsDB; 54762; -.
DR   Antibodypedia; 2079; 463 antibodies from 33 providers.
DR   DNASU; 5596; -.
DR   Ensembl; ENST00000400384.7; ENSP00000383234.1; ENSG00000141639.12.
DR   GeneID; 5596; -.
DR   KEGG; hsa:5596; -.
DR   MANE-Select; ENST00000400384.7; ENSP00000383234.1; NM_002747.4; NP_002738.2.
DR   UCSC; uc002lev.4; human.
DR   AGR; HGNC:6878; -.
DR   CTD; 5596; -.
DR   DisGeNET; 5596; -.
DR   GeneCards; MAPK4; -.
DR   HGNC; HGNC:6878; MAPK4.
DR   HPA; ENSG00000141639; Tissue enhanced (brain, parathyroid gland).
DR   MIM; 176949; gene.
DR   neXtProt; NX_P31152; -.
DR   OpenTargets; ENSG00000141639; -.
DR   PharmGKB; PA30623; -.
DR   VEuPathDB; HostDB:ENSG00000141639; -.
DR   eggNOG; KOG0660; Eukaryota.
DR   GeneTree; ENSGT00940000159850; -.
DR   HOGENOM; CLU_000288_181_15_1; -.
DR   InParanoid; P31152; -.
DR   OMA; QGPLFYP; -.
DR   OrthoDB; 5344491at2759; -.
DR   PhylomeDB; P31152; -.
DR   TreeFam; TF105098; -.
DR   BRENDA; 2.7.11.24; 2681.
DR   PathwayCommons; P31152; -.
DR   Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR   SignaLink; P31152; -.
DR   SIGNOR; P31152; -.
DR   BioGRID-ORCS; 5596; 8 hits in 1153 CRISPR screens.
DR   ChiTaRS; MAPK4; human.
DR   GeneWiki; MAPK4; -.
DR   GenomeRNAi; 5596; -.
DR   Pharos; P31152; Tbio.
DR   PRO; PR:P31152; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   RNAct; P31152; Protein.
DR   Bgee; ENSG00000141639; Expressed in caudate nucleus and 89 other cell types or tissues.
DR   ExpressionAtlas; P31152; baseline and differential.
DR   Genevisible; P31152; HS.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004707; F:MAP kinase activity; TAS:ProtInc.
DR   GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR   CDD; cd07854; STKc_MAPK4_6; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR008350; MAPK_ERK3/4.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR   PANTHER; PTHR24055:SF25; MITOGEN-ACTIVATED PROTEIN KINASE 4; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   PRINTS; PR01771; ERK3ERK4MAPK.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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   ATP-binding; Cell cycle; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
FT   CHAIN           1..587
FT                   /note="Mitogen-activated protein kinase 4"
FT                   /id="PRO_0000186254"
FT   DOMAIN          20..312
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          373..413
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          499..534
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           186..188
FT                   /note="SEG motif"
FT   MOTIF           328..333
FT                   /note="FRIEDE motif"
FT   COMPBIAS        393..413
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        149
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         26..34
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         49
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         186
FT                   /note="Phosphoserine; by PAK1, PAK2 and PAK3"
FT                   /evidence="ECO:0000269|PubMed:21177870,
FT                   ECO:0007744|PubMed:18669648"
FT   MOD_RES         434
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         38
FT                   /note="V -> M (in dbSNP:rs3752087)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042254"
FT   VARIANT         371
FT                   /note="R -> P (in dbSNP:rs3752089)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042255"
FT   CONFLICT        220
FT                   /note="A -> S (in Ref. 5; AAH50299)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   587 AA;  65922 MW;  71DB32D1E63EF8EE CRC64;
     MAEKGDCIAS VYGYDLGGRF VDFQPLGFGV NGLVLSAVDS RACRKVAVKK IALSDARSMK
     HALREIKIIR RLDHDNIVKV YEVLGPKGTD LQGELFKFSV AYIVQEYMET DLARLLEQGT
     LAEEHAKLFM YQLLRGLKYI HSANVLHRDL KPANIFISTE DLVLKIGDFG LARIVDQHYS
     HKGYLSEGLV TKWYRSPRLL LSPNNYTKAI DMWAAGCILA EMLTGRMLFA GAHELEQMQL
     ILETIPVIRE EDKDELLRVM PSFVSSTWEV KRPLRKLLPE VNSEAIDFLE KILTFNPMDR
     LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AANQSQLSNW DTCSSRYPVS
     LSSDLEWRPD RCQDASEVQR DPRAGSAPLA EDVQVDPRKD SHSSSERFLE QSHSSMERAF
     EADYGRSCDY KVGSPSYLDK LLWRDNKPHH YSEPKLILDL SHWKQAAGAP PTATGLADTG
     AREDEPASLF LEIAQWVKST QGGPEHASPP ADDPERRLSA SPPGRPAPVD GGASPQFDLD
     VFISRALKLC TKPEDLPDNK LGDLNGACIP EHPGDLVQTE AFSKERW
//
ID   B4DEW2_HUMAN            Unreviewed;       376 AA.
AC   B4DEW2;
DT   23-SEP-2008, integrated into UniProtKB/TrEMBL.
DT   23-SEP-2008, sequence version 1.
DT   24-JAN-2024, entry version 103.
DE   RecName: Full=mitogen-activated protein kinase {ECO:0000256|ARBA:ARBA00012411};
DE            EC=2.7.11.24 {ECO:0000256|ARBA:ARBA00012411};
GN   Name=MAPK4 {ECO:0000313|Ensembl:ENSP00000439231.1};
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:0000313|EMBL:BAG57223.1};
RN   [1] {ECO:0000313|Ensembl:ENSP00000439231.1, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16177791; DOI=10.1038/nature03983;
RA   Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA   Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA   Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA   Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA   Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA   Noguchi H., O'Leary S.B., O'Neill K., Piqani B., Smith C.L., Talamas J.A.,
RA   Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q.,
RA   Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 18.";
RL   Nature 437:551-555(2005).
RN   [2] {ECO:0000313|EMBL:BAG57223.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Cerebellum {ECO:0000313|EMBL:BAG57223.1};
RA   Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A.,
RA   Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y.,
RA   Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T.,
RA   Sugano S., Nomura N., Isogai T.;
RT   "NEDO human cDNA sequencing project focused on splicing variants.";
RL   Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0007829|PubMed:23186163}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=23186163;
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   [4] {ECO:0000313|Ensembl:ENSP00000439231.1}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (SEP-2023) to UniProtKB.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|ARBA:ARBA00001946};
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DR   EMBL; AC012433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090638; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK293818; BAG57223.1; -; mRNA.
DR   RefSeq; NP_001278968.1; NM_001292039.1.
DR   MassIVE; B4DEW2; -.
DR   ProteomicsDB; 3987; -.
DR   Antibodypedia; 2079; 463 antibodies from 33 providers.
DR   DNASU; 5596; -.
DR   Ensembl; ENST00000540640.3; ENSP00000439231.1; ENSG00000141639.12.
DR   GeneID; 5596; -.
DR   UCSC; uc010xdm.3; human.
DR   CTD; 5596; -.
DR   HGNC; HGNC:6878; MAPK4.
DR   VEuPathDB; HostDB:ENSG00000141639; -.
DR   GeneTree; ENSGT00940000159850; -.
DR   OMA; QGPLFYP; -.
DR   OrthoDB; 5344491at2759; -.
DR   BioGRID-ORCS; 5596; 8 hits in 1153 CRISPR screens.
DR   ChiTaRS; MAPK4; human.
DR   GenomeRNAi; 5596; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   Bgee; ENSG00000141639; Expressed in caudate nucleus and 89 other cell types or tissues.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0004707; F:MAP kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR008350; MAPK_ERK3/4.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR   PANTHER; PTHR24055:SF25; MITOGEN-ACTIVATED PROTEIN KINASE 4; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   PRINTS; PR01771; ERK3ERK4MAPK.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE   1: Evidence at protein level;
KW   Kinase {ECO:0000313|EMBL:BAG57223.1};
KW   Proteomics identification {ECO:0007829|MaxQB:B4DEW2,
KW   ECO:0007829|PeptideAtlas:B4DEW2};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Transferase {ECO:0000313|EMBL:BAG57223.1}.
FT   DOMAIN          1..101
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   REGION          162..202
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          288..323
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        182..202
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   376 AA;  42093 MW;  5C3D836FDF091BF6 CRC64;
     MWAAGCILAE MLTGRMLFAG AHELEQMQLI LETIPVIREE DKDELLRVMP SFVSSTWEVK
     RPLRKLLPEV NSEAIDFLEK ILTFNPMDRL TAEMGLQHPY MSPYSCPEDE PTSQHPFRIE
     DEIDDIVLMA ANQSQLSNWD TCSSRYPVSL SSDLEWRPDR CQDASEVQRD PRAGSAPLAE
     DVQVDPRKDS HSSSERFLEQ SHSSMERAFE ADYGRSCDYK VGSPSYLDKL LWRDNKPHHY
     SEPKLILDLS HWKQAAGAPP TATGLADTGA REDEPASLFL EIAQWVKSTQ GGPEHASPPA
     DDPERRLSAS PPGRPAPVDG GASPQFDLDV FISRALKLCT KPEDLPDNKL GDLNGACIPE
     HPGDLVQTEA FSKERW
//
ID   K7ELV1_HUMAN            Unreviewed;       233 AA.
AC   K7ELV1;
DT   09-JAN-2013, integrated into UniProtKB/TrEMBL.
DT   09-JAN-2013, sequence version 1.
DT   24-JAN-2024, entry version 73.
DE   RecName: Full=mitogen-activated protein kinase {ECO:0000256|ARBA:ARBA00012411};
DE            EC=2.7.11.24 {ECO:0000256|ARBA:ARBA00012411};
GN   Name=MAPK4 {ECO:0000313|Ensembl:ENSP00000466233.1};
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:0000313|Ensembl:ENSP00000466233.1, ECO:0000313|Proteomes:UP000005640};
RN   [1] {ECO:0000313|Ensembl:ENSP00000466233.1, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16177791; DOI=10.1038/nature03983;
RA   Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA   Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA   Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA   Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA   Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA   Noguchi H., O'Leary S.B., O'Neill K., Piqani B., Smith C.L., Talamas J.A.,
RA   Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q.,
RA   Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 18.";
RL   Nature 437:551-555(2005).
RN   [2] {ECO:0007829|PubMed:18669648}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [3] {ECO:0000313|Ensembl:ENSP00000466233.1}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (SEP-2023) to UniProtKB.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|ARBA:ARBA00001946};
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily.
CC       {ECO:0000256|RuleBase:RU000304}.
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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; AC012433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090638; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001278969.1; NM_001292040.1.
DR   AlphaFoldDB; K7ELV1; -.
DR   SMR; K7ELV1; -.
DR   MassIVE; K7ELV1; -.
DR   MaxQB; K7ELV1; -.
DR   PeptideAtlas; K7ELV1; -.
DR   Antibodypedia; 2079; 463 antibodies from 33 providers.
DR   DNASU; 5596; -.
DR   Ensembl; ENST00000592595.5; ENSP00000466233.1; ENSG00000141639.12.
DR   GeneID; 5596; -.
DR   UCSC; uc010doz.4; human.
DR   CTD; 5596; -.
DR   HGNC; HGNC:6878; MAPK4.
DR   VEuPathDB; HostDB:ENSG00000141639; -.
DR   GeneTree; ENSGT00940000159850; -.
DR   HOGENOM; CLU_000288_181_1_1; -.
DR   OrthoDB; 5344491at2759; -.
DR   BioGRID-ORCS; 5596; 8 hits in 1153 CRISPR screens.
DR   ChiTaRS; MAPK4; human.
DR   GenomeRNAi; 5596; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   Bgee; ENSG00000141639; Expressed in caudate nucleus and 89 other cell types or tissues.
DR   ExpressionAtlas; K7ELV1; baseline and differential.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004707; F:MAP kinase activity; IEA:UniProtKB-EC.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR008350; MAPK_ERK3/4.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR   PANTHER; PTHR24055:SF25; MITOGEN-ACTIVATED PROTEIN KINASE 4; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   PRINTS; PR01771; ERK3ERK4MAPK.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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   ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW   ProRule:PRU10141}; Kinase {ECO:0000256|RuleBase:RU000304};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW   ProRule:PRU10141}; Nucleus {ECO:0000256|ARBA:ARBA00023242};
KW   Proteomics identification {ECO:0007829|MaxQB:K7ELV1,
KW   ECO:0007829|PeptideAtlas:K7ELV1};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Serine/threonine-protein kinase {ECO:0000256|RuleBase:RU000304};
KW   Transferase {ECO:0000256|RuleBase:RU000304}.
FT   DOMAIN          20..233
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   BINDING         50
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
SQ   SEQUENCE   233 AA;  26186 MW;  953BE9B3AD82A0B5 CRC64;
     MAEKGDCIAS VYGYDLGGRF VDFQPLGFGV NGLVLSAVDS RACRKVAVKK IALSDARSMK
     HALREIKIIR RLDHDNIVKV YEVLGPKGTD LQGELFKFSV AYIVQEYMET DLARLLEQGT
     LAEEHAKLFM YQLLRGLKYI HSANVLHRDL KPANIFISTE DLVLKIGDFG LARIVDQHYS
     HKGYLSEGLV TKWYRSPRLL LSPNNYTKAI DMWAAGCILA EMLTGRMLFA GTL
//
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