LOCUS       NP_002738                587 aa            linear   PRI 28-APR-2025
DEFINITION  mitogen-activated protein kinase 4 isoform 1 [Homo sapiens].
ACCESSION   NP_002738
VERSION     NP_002738.2
DBSOURCE    REFSEQ: accession NM_002747.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 587)
  AUTHORS   Fan,Z., Huang,Q., Zhang,Z., Han,L., Fang,X., Yang,K., Huang,G.,
            Zheng,Z., Yawalkar,N., Lin,Y., Wang,Z. and Yan,K.
  TITLE     Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with
            Clinical Response to Methotrexate in Patients with Psoriasis
  JOURNAL   Dermatology 240 (1), 111-118 (2024)
   PUBMED   37494889
  REMARK    GeneRIF: Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated
            with Clinical Response to Methotrexate in Patients with Psoriasis.
REFERENCE   2  (residues 1 to 587)
  AUTHORS   Zhang,Z., Lan,H. and Zhao,S.
  TITLE     LINC00467 enhanced the proliferative, migratory and invasive
            ability of breast cancer cells by targeting miR-18a/b-5p/MAPK4 axis
  JOURNAL   Cell Mol Biol (Noisy-le-grand) 69 (14), 88-93 (2023)
   PUBMED   38279470
  REMARK    GeneRIF: LINC00467 enhanced the proliferative, migratory and
            invasive ability of breast cancer cells by targeting
            miR-18a/b-5p/MAPK4 axis.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 587)
  AUTHORS   Han,D., Wang,W., Jeon,J.H., Shen,T., Huang,X., Yi,P., Dong,B. and
            Yang,F.
  TITLE     Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer
            growth and resistance to therapy
  JOURNAL   PLoS Biol 21 (8), e3002227 (2023)
   PUBMED   37531320
  REMARK    GeneRIF: Cooperative activation of PDK1 and AKT by MAPK4 enhances
            cancer growth and resistance to therapy.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 587)
  AUTHORS   Segal,D., Maier,S., Mastromarco,G.J., Qian,W.W., Nabeel-Shah,S.,
            Lee,H., Moore,G., Lacoste,J., Larsen,B., Lin,Z.Y.,
            Selvabaskaran,A., Liu,K., Smibert,C., Zhang,Z., Greenblatt,J.,
            Peng,J., Lee,H.O., Gingras,A.C. and Taipale,M.
  TITLE     A central chaperone-like role for 14-3-3 proteins in human cells
  JOURNAL   Mol Cell 83 (6), 974-993 (2023)
   PUBMED   36931259
REFERENCE   5  (residues 1 to 587)
  AUTHORS   Guan,W., Li,S., Zhang,Z., Xiao,H., He,J., Li,J., He,X., Luo,J.,
            Liu,Y., Lei,L., Ma,J., Chen,L. and Chen,C.
  TITLE     Promotor methylation status of MAPK4 is a novel epigenetic
            biomarker for prognosis of recurrence in patients with thymic
            epithelial tumors
  JOURNAL   Thorac Cancer 13 (20), 2844-2853 (2022)
   PUBMED   36073321
  REMARK    GeneRIF: Promotor methylation status of MAPK4 is a novel epigenetic
            biomarker for prognosis of recurrence in patients with thymic
            epithelial tumors.
REFERENCE   6  (residues 1 to 587)
  AUTHORS   Davis,R.J.
  TITLE     Transcriptional regulation by MAP kinases
  JOURNAL   Mol Reprod Dev 42 (4), 459-467 (1995)
   PUBMED   8607977
  REMARK    Review article
REFERENCE   7  (residues 1 to 587)
  AUTHORS   Seger,R. and Krebs,E.G.
  TITLE     The MAPK signaling cascade
  JOURNAL   FASEB J 9 (9), 726-735 (1995)
   PUBMED   7601337
  REMARK    Review article
REFERENCE   8  (residues 1 to 587)
  AUTHORS   Zhu,A.X., Zhao,Y., Moller,D.E. and Flier,J.S.
  TITLE     Cloning and characterization of p97MAPK, a novel human homolog of
            rat ERK-3
  JOURNAL   Mol Cell Biol 14 (12), 8202-8211 (1994)
   PUBMED   7969157
REFERENCE   9  (residues 1 to 587)
  AUTHORS   Li,L., Wysk,M., Gonzalez,F.A. and Davis,R.J.
  TITLE     Genomic loci of human mitogen-activated protein kinases
  JOURNAL   Oncogene 9 (2), 647-649 (1994)
   PUBMED   8290275
REFERENCE   10 (residues 1 to 587)
  AUTHORS   Gonzalez,F.A., Raden,D.L., Rigby,M.R. and Davis,R.J.
  TITLE     Heterogeneous expression of four MAP kinase isoforms in human
            tissues
  JOURNAL   FEBS Lett 304 (2-3), 170-178 (1992)
   PUBMED   1319925
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC090638.11, BC050299.1,
            X59727.1, BC040493.1 and AI088913.1.
            
            On Mar 9, 2006 this sequence version replaced NP_002738.1.
            
            Summary: Mitogen-activated protein kinase 4 is a member of the
            mitogen-activated protein kinase family. Tyrosine kinase growth
            factor receptors activate mitogen-activated protein kinases which
            then translocate into the nucleus and phosphorylate nuclear
            targets. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, May 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC050299.1, AK295058.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1970526, SAMEA2144120
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000400384.7/ ENSP00000383234.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..587
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q21.1-q21.2"
     Protein         1..587
                     /product="mitogen-activated protein kinase 4 isoform 1"
                     /EC_number="2.7.11.24"
                     /note="Erk3-related; extracellular signal-regulated kinase
                     4; MAPK 4"
                     /calculated_mol_wt=65791
     Region          14..351
                     /region_name="STKc_MAPK4_6"
                     /note="Catalytic domain of the Serine/Threonine Kinases,
                     Mitogen-Activated Protein Kinases 4 (also called ERK4) and
                     6 (also called ERK3); cd07854"
                     /db_xref="CDD:143359"
     Site            order(26..29,31..32,34,47,49,64,78,105..108,111,113..114,
                     149,151,153..154,156,167..168,171,186,188..191,193,231)
                     /site_type="active"
                     /db_xref="CDD:143359"
     Site            order(26..29,31..32,34,47,49,78,105..108,111,114,151,
                     153..154,156,167..168)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:143359"
     Site            order(64,113,149,151,171,186,188..191,193,231)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:143359"
     Site            order(75,109..110,115,125,128,135,157..160,162,315,317,
                     320)
                     /site_type="other"
                     /note="KIM docking site [polypeptide binding]"
                     /db_xref="CDD:143359"
     Site            167..193
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:143359"
     Region          186..188
                     /region_name="SEG motif"
                     /note="propagated from UniProtKB/Swiss-Prot (P31152.2)"
     Site            186
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by PAK1, PAK2 and PAK3.
                     /evidence=ECO:0000269|PubMed:21177870,
                     ECO:0007744|PubMed:18669648; propagated from
                     UniProtKB/Swiss-Prot (P31152.2)"
     Region          328..333
                     /region_name="FRIEDE motif"
                     /note="propagated from UniProtKB/Swiss-Prot (P31152.2)"
     Region          373..413
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P31152.2)"
     Site            434
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (P31152.2)"
     Region          499..534
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P31152.2)"
     CDS             1..587
                     /gene="MAPK4"
                     /gene_synonym="ERK-4; ERK4; p63-MAPK; p63MAPK; PRKM4"
                     /coded_by="NM_002747.4:1028..2791"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS42437.1"
                     /db_xref="GeneID:5596"
                     /db_xref="HGNC:HGNC:6878"
                     /db_xref="MIM:176949"
ORIGIN      
        1 maekgdcias vygydlggrf vdfqplgfgv nglvlsavds racrkvavkk ialsdarsmk
       61 halreikiir rldhdnivkv yevlgpkgtd lqgelfkfsv ayivqeymet dlarlleqgt
      121 laeehaklfm yqllrglkyi hsanvlhrdl kpanifiste dlvlkigdfg larivdqhys
      181 hkgylseglv tkwyrsprll lspnnytkai dmwaagcila emltgrmlfa gaheleqmql
      241 iletipvire edkdellrvm psfvsstwev krplrkllpe vnseaidfle kiltfnpmdr
      301 ltaemglqhp ymspyscped eptsqhpfri edeiddivlm aanqsqlsnw dtcssrypvs
      361 lssdlewrpd rcqdasevqr dpragsapla edvqvdprkd shssserfle qshssmeraf
      421 eadygrscdy kvgspsyldk llwrdnkphh ysepklildl shwkqaagap ptatgladtg
      481 aredepaslf leiaqwvkst qggpehaspp addperrlsa sppgrpapvd ggaspqfdld
      541 vfisralklc tkpedlpdnk lgdlngacip ehpgdlvqte afskerw
//
