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P31152

- MK04_HUMAN

UniProt

P31152 - MK04_HUMAN

Protein

Mitogen-activated protein kinase 4

Gene

MAPK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 2 (25 Nov 2008)
      Previous versions | rss
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    Functioni

    Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activated by phosphorylation at Ser-186.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei49 – 491ATPPROSITE-ProRule annotations
    Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotations

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi26 – 349ATPPROSITE-ProRule annotations

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. MAP kinase activity Source: ProtInc
    3. protein binding Source: IntAct
    4. protein homodimerization activity Source: UniProtKB
    5. protein kinase binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. MAPK cascade Source: GOC
    3. protein phosphorylation Source: ProtInc

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Cell cycle

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 2681.
    SignaLinkiP31152.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 4 (EC:2.7.11.24)
    Short name:
    MAP kinase 4
    Short name:
    MAPK 4
    Alternative name(s):
    Extracellular signal-regulated kinase 4
    Short name:
    ERK-4
    MAP kinase isoform p63
    Short name:
    p63-MAPK
    Gene namesi
    Name:MAPK4
    Synonyms:ERK4, PRKM4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

    Organism-specific databases

    HGNCiHGNC:6878. MAPK4.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity
    Note: Translocates to the cytoplasm following interaction with MAPKAPK5.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30623.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 587587Mitogen-activated protein kinase 4PRO_0000186254Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei186 – 1861Phosphoserine; by PAK1, PAK2 and PAK32 Publications

    Post-translational modificationi

    Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP31152.
    PaxDbiP31152.
    PRIDEiP31152.

    PTM databases

    PhosphoSiteiP31152.

    Expressioni

    Tissue specificityi

    High expression in heart and brain.

    Gene expression databases

    ArrayExpressiP31152.
    BgeeiP31152.
    CleanExiHS_MAPK4.
    GenevestigatoriP31152.

    Organism-specific databases

    HPAiCAB025868.
    HPA007461.

    Interactioni

    Subunit structurei

    Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HSP90AB1P082382EBI-3906061,EBI-352572

    Protein-protein interaction databases

    BioGridi111582. 15 interactions.
    IntActiP31152. 11 interactions.
    STRINGi9606.ENSP00000383234.

    Structurei

    3D structure databases

    ProteinModelPortaliP31152.
    SMRiP31152. Positions 13-316.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini20 – 312293Protein kinasePROSITE-ProRule annotationsAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi186 – 1883SEG motif
    Motifi328 – 3336FRIEDE motif

    Domaini

    The FRIEDE motif is required for docking MAPKAPK5.By similarity
    In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotations

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233020.
    HOVERGENiHBG104376.
    InParanoidiP31152.
    KOiK06855.
    OMAiRCQDASE.
    PhylomeDBiP31152.
    TreeFamiTF105098.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR008350. MAPK_ERK3/4.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    PRINTSiPR01771. ERK3ERK4MAPK.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Sequencei

    Sequence statusi: Complete.

    P31152-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEKGDCIAS VYGYDLGGRF VDFQPLGFGV NGLVLSAVDS RACRKVAVKK    50
    IALSDARSMK HALREIKIIR RLDHDNIVKV YEVLGPKGTD LQGELFKFSV 100
    AYIVQEYMET DLARLLEQGT LAEEHAKLFM YQLLRGLKYI HSANVLHRDL 150
    KPANIFISTE DLVLKIGDFG LARIVDQHYS HKGYLSEGLV TKWYRSPRLL 200
    LSPNNYTKAI DMWAAGCILA EMLTGRMLFA GAHELEQMQL ILETIPVIRE 250
    EDKDELLRVM PSFVSSTWEV KRPLRKLLPE VNSEAIDFLE KILTFNPMDR 300
    LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AANQSQLSNW 350
    DTCSSRYPVS LSSDLEWRPD RCQDASEVQR DPRAGSAPLA EDVQVDPRKD 400
    SHSSSERFLE QSHSSMERAF EADYGRSCDY KVGSPSYLDK LLWRDNKPHH 450
    YSEPKLILDL SHWKQAAGAP PTATGLADTG AREDEPASLF LEIAQWVKST 500
    QGGPEHASPP ADDPERRLSA SPPGRPAPVD GGASPQFDLD VFISRALKLC 550
    TKPEDLPDNK LGDLNGACIP EHPGDLVQTE AFSKERW 587
    Length:587
    Mass (Da):65,922
    Last modified:November 25, 2008 - v2
    Checksum:i71DB32D1E63EF8EE
    GO

    Sequence cautioni

    The sequence CAA42411.1 differs from that shown. Reason: Frameshift at several positions.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti38 – 381V → M.2 Publications
    Corresponds to variant rs3752087 [ dbSNP | Ensembl ].
    VAR_042254
    Natural varianti371 – 3711R → P.1 Publication
    Corresponds to variant rs3752089 [ dbSNP | Ensembl ].
    VAR_042255

    Sequence conflict

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti220 – 2201A → S in AAH50299. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X59727 mRNA. Translation: CAA42411.1. Frameshift.
    AK295058 mRNA. Translation: BAG58107.1.
    AC012433 Genomic DNA. No translation available.
    AC090395 Genomic DNA. No translation available.
    CH471096 Genomic DNA. Translation: EAW62976.1.
    CH471096 Genomic DNA. Translation: EAW62977.1.
    BC050299 mRNA. Translation: AAH50299.1.
    BC117216 mRNA. Translation: AAI17217.1.
    CCDSiCCDS42437.1.
    PIRiS23429.
    RefSeqiNP_002738.2. NM_002747.3.
    XP_005258356.1. XM_005258299.1.
    UniGeneiHs.433728.

    Genome annotation databases

    EnsembliENST00000400384; ENSP00000383234; ENSG00000141639.
    GeneIDi5596.
    KEGGihsa:5596.
    UCSCiuc002lev.3. human.

    Polymorphism databases

    DMDMi215274102.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X59727 mRNA. Translation: CAA42411.1 . Frameshift.
    AK295058 mRNA. Translation: BAG58107.1 .
    AC012433 Genomic DNA. No translation available.
    AC090395 Genomic DNA. No translation available.
    CH471096 Genomic DNA. Translation: EAW62976.1 .
    CH471096 Genomic DNA. Translation: EAW62977.1 .
    BC050299 mRNA. Translation: AAH50299.1 .
    BC117216 mRNA. Translation: AAI17217.1 .
    CCDSi CCDS42437.1.
    PIRi S23429.
    RefSeqi NP_002738.2. NM_002747.3.
    XP_005258356.1. XM_005258299.1.
    UniGenei Hs.433728.

    3D structure databases

    ProteinModelPortali P31152.
    SMRi P31152. Positions 13-316.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111582. 15 interactions.
    IntActi P31152. 11 interactions.
    STRINGi 9606.ENSP00000383234.

    Chemistry

    BindingDBi P31152.
    ChEMBLi CHEMBL5759.
    GuidetoPHARMACOLOGYi 2091.

    PTM databases

    PhosphoSitei P31152.

    Polymorphism databases

    DMDMi 215274102.

    Proteomic databases

    MaxQBi P31152.
    PaxDbi P31152.
    PRIDEi P31152.

    Protocols and materials databases

    DNASUi 5596.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000400384 ; ENSP00000383234 ; ENSG00000141639 .
    GeneIDi 5596.
    KEGGi hsa:5596.
    UCSCi uc002lev.3. human.

    Organism-specific databases

    CTDi 5596.
    GeneCardsi GC18P048125.
    H-InvDB HIX0027373.
    HGNCi HGNC:6878. MAPK4.
    HPAi CAB025868.
    HPA007461.
    MIMi 176949. gene.
    neXtProti NX_P31152.
    PharmGKBi PA30623.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233020.
    HOVERGENi HBG104376.
    InParanoidi P31152.
    KOi K06855.
    OMAi RCQDASE.
    PhylomeDBi P31152.
    TreeFami TF105098.

    Enzyme and pathway databases

    BRENDAi 2.7.11.24. 2681.
    SignaLinki P31152.

    Miscellaneous databases

    GeneWikii MAPK4.
    GenomeRNAii 5596.
    NextBioi 21720.
    PROi P31152.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P31152.
    Bgeei P31152.
    CleanExi HS_MAPK4.
    Genevestigatori P31152.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR008350. MAPK_ERK3/4.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PRINTSi PR01771. ERK3ERK4MAPK.
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Heterogeneous expression of four MAP kinase isoforms in human tissues."
      Gonzalez F.A., Raden D.L., Rigby M.R., Davis R.J.
      FEBS Lett. 304:170-178(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-38.
      Tissue: Brain and Cerebellum.
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    7. "Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway."
      Deleris P., Trost M., Topisirovic I., Tanguay P.L., Borden K.L., Thibault P., Meloche S.
      J. Biol. Chem. 286:6470-6478(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-186.
    8. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-38 AND PRO-371.

    Entry informationi

    Entry nameiMK04_HUMAN
    AccessioniPrimary (citable) accession number: P31152
    Secondary accession number(s): A1A4C4, Q0VG04
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: November 25, 2008
    Last modified: October 1, 2014
    This is version 140 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

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