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Q8TD08

- MK15_HUMAN

UniProt

Q8TD08 - MK15_HUMAN

Protein

Mitogen-activated protein kinase 15

Gene

MAPK15

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    Functioni

    In vitro, phosphorylates MBP.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Activated by threonine and tyrosine phosphorylation. Inhibited by dual specificity phosphatases, such as DUSP1 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei42 – 421ATPPROSITE-ProRule annotation
    Active sitei137 – 1371Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi19 – 279ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. MAP kinase activity Source: UniProtKB
    3. SH3 domain binding Source: UniProtKB

    GO - Biological processi

    1. MAPK cascade Source: GOC
    2. negative regulation of DNA replication Source: Ensembl
    3. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    4. positive regulation of protein catabolic process Source: Ensembl
    5. positive regulation of protein phosphorylation Source: Ensembl
    6. positive regulation of protein ubiquitination Source: Ensembl
    7. protein autophosphorylation Source: UniProtKB
    8. response to estradiol Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ8TD08.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 15 (EC:2.7.11.24)
    Short name:
    MAP kinase 15
    Short name:
    MAPK 15
    Alternative name(s):
    Extracellular signal-regulated kinase 7
    Short name:
    ERK-7
    Extracellular signal-regulated kinase 8
    Short name:
    ERK-8
    Gene namesi
    Name:MAPK15
    Synonyms:ERK7, ERK8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:24667. MAPK15.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB
    2. intracellular Source: UniProtKB
    3. nucleus Source: Ensembl

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi42 – 421K → R: Loss of autophosphorylation and activity. 1 Publication
    Mutagenesisi175 – 1751T → A: Loss of autophosphorylation and activity. 1 Publication
    Mutagenesisi177 – 1771Y → A: Loss of autophosphorylation and activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA142671478.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 544544Mitogen-activated protein kinase 15PRO_0000232637Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei175 – 1751Phosphothreonine1 Publication
    Modified residuei177 – 1771Phosphotyrosine1 Publication
    Modified residuei415 – 4151Phosphoserine1 Publication

    Post-translational modificationi

    Dually phosphorylated on Thr-175 and Tyr-177, which activates the enzyme. Autophosphorylated on threonine and tyrosine residues in vitro.2 Publications
    Ubiquitinated. Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ8TD08.
    PaxDbiQ8TD08.
    PRIDEiQ8TD08.

    PTM databases

    PhosphoSiteiQ8TD08.

    Expressioni

    Tissue specificityi

    Widely expressed with a maximal expression in lung and kidney.2 Publications

    Gene expression databases

    BgeeiQ8TD08.
    CleanExiHS_MAPK15.
    GenevestigatoriQ8TD08.

    Organism-specific databases

    HPAiHPA002704.

    Interactioni

    Subunit structurei

    Interacts with CSK/c-Src, ABL1, RET and TGFB1I1.3 Publications

    Protein-protein interaction databases

    BioGridi128827. 18 interactions.
    IntActiQ8TD08. 9 interactions.
    STRINGi9606.ENSP00000337691.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8TD08.
    SMRiQ8TD08. Positions 5-402.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 304292Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi175 – 1773TXY

    Domaini

    The N-terminal region (1-20) is the minimal region necessary for ubiquitination and further proteasomal degradation.By similarity
    The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    KOiK08293.
    OMAiCTVKLCD.
    OrthoDBiEOG7VDXPC.
    PhylomeDBiQ8TD08.
    TreeFamiTF105101.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8TD08-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MCTVVDPRIV RRYLLRRQLG QGAYGIVWKA VDRRTGEVVA IKKIFDAFRD    50
    KTDAQRTFRE ITLLQEFGDH PNIISLLDVI RAENDRDIYL VFEFMDTDLN 100
    AVIRKGGLLQ DVHVRSIFYQ LLRATRFLHS GHVVHRDQKP SNVLLDANCT 150
    VKLCDFGLAR SLGDLPEGPE DQAVTEYVAT RWYRAPEVLL SSHRYTLGVD 200
    MWSLGCILGE MLRGRPLFPG TSTLHQLELI LETIPPPSEE DLLALGSGCR 250
    ASVLHQLGSR PRQTLDALLP PDTSPEALDL LRRLLVFAPD KRLSATQALQ 300
    HPYVQRFHCP SDEWAREADV RPRAHEGVQL SVPEYRSRVY QMILECGGSS 350
    GTSREKGPEG VSPSQAHLHK PRADPQLPSR TPVQGPRPRP QSSPGHDPAE 400
    HESPRAAKNV PRQNSAPLLQ TALLGNGERP PGAKEAPPLT LSLVKPSGRG 450
    AAPSLTSQAA AQVANQALIR GDWNRGGGVR VASVQQVPPR LPPEARPGRR 500
    MFSTSALQGA QGGARALLGG YSQAYGTVCH SALGHLPLLE GHHV 544
    Length:544
    Mass (Da):59,832
    Last modified:June 1, 2002 - v1
    Checksum:i758E0E3B9654AAC5
    GO
    Isoform 2 (identifier: Q8TD08-2) [UniParc]FASTAAdd to Basket

    Also known as: Erk8 delta

    The sequence of this isoform differs from the canonical sequence as follows:
         241-254: DLLALGSGCRASVL → GAQTACRSGTGAST
         255-544: Missing.

    Note: Appears not to be a CSK- and RET-dependent activated kinase.

    Show »
    Length:254
    Mass (Da):28,696
    Checksum:i88FC081FFB15644A
    GO
    Isoform 3 (identifier: Q8TD08-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         95-95: M → MGCPPSPPPPTAVRTLSA
         261-544: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:277
    Mass (Da):31,112
    Checksum:i07B9D39A696701D0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti113 – 1131H → R in AAY44299. (PubMed:16484222)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti221 – 2211T → K.
    Corresponds to variant rs60732298 [ dbSNP | Ensembl ].
    VAR_061535
    Natural varianti505 – 5051S → P.
    Corresponds to variant rs56038219 [ dbSNP | Ensembl ].
    VAR_061536

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei95 – 951M → MGCPPSPPPPTAVRTLSA in isoform 3. 1 PublicationVSP_017918
    Alternative sequencei241 – 25414DLLAL…RASVL → GAQTACRSGTGAST in isoform 2. 1 PublicationVSP_017919Add
    BLAST
    Alternative sequencei255 – 544290Missing in isoform 2. 1 PublicationVSP_017920Add
    BLAST
    Alternative sequencei261 – 544284Missing in isoform 3. 1 PublicationVSP_017921Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY065978 mRNA. Translation: AAL40897.1.
    AY994058 mRNA. Translation: AAY44299.1.
    BC028034 mRNA. Translation: AAH28034.1.
    CCDSiCCDS6409.2. [Q8TD08-1]
    RefSeqiNP_620590.2. NM_139021.2. [Q8TD08-1]
    UniGeneiHs.493169.

    Genome annotation databases

    EnsembliENST00000338033; ENSP00000337691; ENSG00000181085. [Q8TD08-1]
    ENST00000395107; ENSP00000378539; ENSG00000181085. [Q8TD08-3]
    ENST00000395108; ENSP00000378540; ENSG00000181085. [Q8TD08-2]
    GeneIDi225689.
    KEGGihsa:225689.
    UCSCiuc003yzj.3. human. [Q8TD08-1]

    Polymorphism databases

    DMDMi74760462.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY065978 mRNA. Translation: AAL40897.1 .
    AY994058 mRNA. Translation: AAY44299.1 .
    BC028034 mRNA. Translation: AAH28034.1 .
    CCDSi CCDS6409.2. [Q8TD08-1 ]
    RefSeqi NP_620590.2. NM_139021.2. [Q8TD08-1 ]
    UniGenei Hs.493169.

    3D structure databases

    ProteinModelPortali Q8TD08.
    SMRi Q8TD08. Positions 5-402.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 128827. 18 interactions.
    IntActi Q8TD08. 9 interactions.
    STRINGi 9606.ENSP00000337691.

    Chemistry

    BindingDBi Q8TD08.
    ChEMBLi CHEMBL5198.
    GuidetoPHARMACOLOGYi 2090.

    PTM databases

    PhosphoSitei Q8TD08.

    Polymorphism databases

    DMDMi 74760462.

    Proteomic databases

    MaxQBi Q8TD08.
    PaxDbi Q8TD08.
    PRIDEi Q8TD08.

    Protocols and materials databases

    DNASUi 225689.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000338033 ; ENSP00000337691 ; ENSG00000181085 . [Q8TD08-1 ]
    ENST00000395107 ; ENSP00000378539 ; ENSG00000181085 . [Q8TD08-3 ]
    ENST00000395108 ; ENSP00000378540 ; ENSG00000181085 . [Q8TD08-2 ]
    GeneIDi 225689.
    KEGGi hsa:225689.
    UCSCi uc003yzj.3. human. [Q8TD08-1 ]

    Organism-specific databases

    CTDi 225689.
    GeneCardsi GC08P144798.
    HGNCi HGNC:24667. MAPK15.
    HPAi HPA002704.
    neXtProti NX_Q8TD08.
    PharmGKBi PA142671478.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    KOi K08293.
    OMAi CTVKLCD.
    OrthoDBi EOG7VDXPC.
    PhylomeDBi Q8TD08.
    TreeFami TF105101.

    Enzyme and pathway databases

    SignaLinki Q8TD08.

    Miscellaneous databases

    GeneWikii MAPK15.
    GenomeRNAii 225689.
    NextBioi 91718.
    PROi Q8TD08.

    Gene expression databases

    Bgeei Q8TD08.
    CleanExi HS_MAPK15.
    Genevestigatori Q8TD08.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH CSK, MUTAGENESIS OF LYS-42; THR-175 AND TYR-177, PHOSPHORYLATION AT THR-175 AND TYR-177, CHARACTERIZATION, FUNCTION.
      Tissue: Testis.
    2. "Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene."
      Iavarone C., Acunzo M., Carlomagno F., Catania A., Melillo R.M., Carlomagno S.M., Santoro M., Chiariello M.
      J. Biol. Chem. 281:10567-10576(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, FUNCTION, INTERACTION WITH ABL1 AND RET.
      Tissue: Medulla oblongata.
    3. "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] (ISOFORM 3).
      Tissue: Brain.
    4. "ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5."
      Saelzler M.P., Spackman C.C., Liu Y., Martinez L.C., Harris J.P., Abe M.K.
      J. Biol. Chem. 281:16821-16832(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TGFB1I1.
    5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiMK15_HUMAN
    AccessioniPrimary (citable) accession number: Q8TD08
    Secondary accession number(s): Q2TCF9, Q8N362
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 18, 2006
    Last sequence update: June 1, 2002
    Last modified: October 1, 2014
    This is version 110 of the entry and version 1 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 8
      Human chromosome 8: 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. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3