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Q02779

- M3K10_HUMAN

UniProt

Q02779 - M3K10_HUMAN

Protein

Mitogen-activated protein kinase kinase kinase 10

Gene

MAP3K10

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 3 (17 Apr 2007)
      Previous versions | rss
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    Functioni

    Activates the JUN N-terminal pathway.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei125 – 1251ATPPROSITE-ProRule annotation
    Active sitei222 – 2221Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi104 – 1129ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. bHLH transcription factor binding Source: UniProtKB
    3. JUN kinase kinase kinase activity Source: UniProtKB
    4. protein homodimerization activity Source: UniProtKB
    5. protein kinase activity Source: ProtInc
    6. protein serine/threonine kinase activity Source: UniProtKB
    7. transcription corepressor activity Source: UniProtKB

    GO - Biological processi

    1. activation of JNKK activity Source: GOC
    2. activation of JUN kinase activity Source: UniProtKB
    3. apoptotic process Source: ProtInc
    4. JNK cascade Source: ProtInc
    5. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    6. negative regulation of transcription, DNA-templated Source: UniProtKB
    7. peptidyl-serine phosphorylation Source: UniProtKB
    8. peptidyl-threonine phosphorylation Source: UniProtKB
    9. positive regulation of apoptotic process Source: Ensembl
    10. positive regulation of JNK cascade Source: UniProtKB
    11. positive regulation of JUN kinase activity Source: UniProtKB
    12. protein autophosphorylation Source: UniProtKB
    13. signal transduction Source: ProtInc
    14. smoothened signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ02779.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 10 (EC:2.7.11.25)
    Alternative name(s):
    Mixed lineage kinase 2
    Protein kinase MST
    Gene namesi
    Name:MAP3K10
    Synonyms:MLK2, MST
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:6849. MAP3K10.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30593.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 954954Mitogen-activated protein kinase kinase kinase 10PRO_0000086259Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei258 – 2581Phosphothreonine; by autocatalysisBy similarity
    Modified residuei262 – 2621Phosphoserine; by autocatalysis and MAP4K1By similarity
    Modified residuei498 – 4981Phosphoserine1 Publication
    Modified residuei502 – 5021Phosphoserine1 Publication
    Modified residuei506 – 5061Phosphoserine1 Publication
    Modified residuei558 – 5581Phosphothreonine1 Publication

    Post-translational modificationi

    Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ02779.
    PRIDEiQ02779.

    PTM databases

    PhosphoSiteiQ02779.

    Expressioni

    Tissue specificityi

    Expressed in brain and skeletal muscle.

    Gene expression databases

    ArrayExpressiQ02779.
    BgeeiQ02779.
    CleanExiHS_MAP3K10.
    GenevestigatoriQ02779.

    Organism-specific databases

    HPAiHPA007039.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi110440. 25 interactions.
    IntActiQ02779. 3 interactions.
    STRINGi9606.ENSP00000253055.

    Structurei

    Secondary structure

    1
    954
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi20 – 234
    Beta strandi42 – 476
    Helixi50 – 534
    Beta strandi58 – 625
    Beta strandi68 – 725
    Helixi73 – 753

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2RF0X-ray2.00A/B/C/D13-78[»]
    ProteinModelPortaliQ02779.
    SMRiQ02779. Positions 17-78, 92-385.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ02779.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 8166SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini98 – 360263Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni384 – 40522Leucine-zipper 1Add
    BLAST
    Regioni419 – 44022Leucine-zipper 2Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi2 – 54Poly-Glu
    Compositional biasi449 – 46315Arg/Lys-rich (basic)Add
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000060081.
    HOVERGENiHBG067662.
    InParanoidiQ02779.
    KOiK04418.
    OMAiKGHFKKS.
    OrthoDBiEOG7D85VN.
    PhylomeDBiQ02779.
    TreeFamiTF105118.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR015785. MAP3K10.
    IPR016231. MAPKKK9/10/11.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001452. SH3_domain.
    [Graphical view]
    PANTHERiPTHR23257:SF370. PTHR23257:SF370. 1 hit.
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000556. MAPKKK9_11. 1 hit.
    PRINTSiPR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q02779-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEEEEGAVAK EWGTTPAGPV WTAVFDYEAA GDEELTLRRG DRVQVLSQDC    50
    AVSGDEGWWT GQLPSGRVGV FPSNYVAPGA PAAPAGLQLP QEIPFHELQL 100
    EEIIGVGGFG KVYRALWRGE EVAVKAARLD PEKDPAVTAE QVCQEARLFG 150
    ALQHPNIIAL RGACLNPPHL CLVMEYARGG ALSRVLAGRR VPPHVLVNWA 200
    VQVARGMNYL HNDAPVPIIH RDLKSINILI LEAIENHNLA DTVLKITDFG 250
    LAREWHKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE 300
    VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFARLLEECW DPDPHGRPDF 350
    GSILKRLEVI EQSALFQMPL ESFHSLQEDW KLEIQHMFDD LRTKEKELRS 400
    REEELLRAAQ EQRFQEEQLR RREQELAERE MDIVERELHL LMCQLSQEKP 450
    RVRKRKGNFK RSRLLKLREG GSHISLPSGF EHKITVQASP TLDKRKGSDG 500
    ASPPASPSII PRLRAIRLTP VDCGGSSSGS SSGGSGTWSR GGPPKKEELV 550
    GGKKKGRTWG PSSTLQKERV GGEERLKGLG EGSKQWSSSA PNLGKSPKHT 600
    PIAPGFASLN EMEEFAEAED GGSSVPPSPY STPSYLSVPL PAEPSPGARA 650
    PWEPTPSAPP ARWGHGARRR CDLALLGCAT LLGAVGLGAD VAEARAADGE 700
    EQRRWLDGLF FPRAGRFPRG LSPPARPHGR REDVGPGLGL APSATLVSLS 750
    SVSDCNSTRS LLRSDSDEAA PAAPSPPPSP PAPTPTPSPS TNPLVDLELE 800
    SFKKDPRQSL TPTHVTAACA VSRGHRRTPS DGALGQRGPP EPAGHGPGPR 850
    DLLDFPRLPD PQALFPARRR PPEFPGRPTT LTFAPRPRPA ASRPRLDPWK 900
    LVSFGRTLTI SPPSRPDTPE SPGPPSVQPT LLDMDMEGQN QDSTVPLCGA 950
    HGSH 954
    Length:954
    Mass (Da):103,694
    Last modified:April 17, 2007 - v3
    Checksum:i59A7596B05751981
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti462 – 4643SRL → AV in CAA88531. (PubMed:7731697)Curated
    Sequence conflicti465 – 48016LKLRE…LPSGF → AQAAGRRQPHQPALWL(PubMed:8477742)CuratedAdd
    BLAST
    Sequence conflicti471 – 4711G → S in CAA88531. (PubMed:7731697)Curated
    Sequence conflicti807 – 8071R → G in CAA62351. (PubMed:8536694)Curated
    Sequence conflicti818 – 8181A → V in CAA62351. (PubMed:8536694)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti107 – 1071G → E in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_040702
    Natural varianti168 – 1681P → Q.
    Corresponds to variant rs36102209 [ dbSNP | Ensembl ].
    VAR_051639

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X90846 mRNA. Translation: CAA62351.1.
    Z48615 mRNA. Translation: CAA88531.1.
    CCDSiCCDS12549.1.
    PIRiS68178.
    RefSeqiNP_002437.2. NM_002446.3.
    UniGeneiHs.466743.

    Genome annotation databases

    EnsembliENST00000253055; ENSP00000253055; ENSG00000130758.
    GeneIDi4294.
    KEGGihsa:4294.
    UCSCiuc002ona.3. human.

    Polymorphism databases

    DMDMi145559494.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X90846 mRNA. Translation: CAA62351.1 .
    Z48615 mRNA. Translation: CAA88531.1 .
    CCDSi CCDS12549.1.
    PIRi S68178.
    RefSeqi NP_002437.2. NM_002446.3.
    UniGenei Hs.466743.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2RF0 X-ray 2.00 A/B/C/D 13-78 [» ]
    ProteinModelPortali Q02779.
    SMRi Q02779. Positions 17-78, 92-385.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110440. 25 interactions.
    IntActi Q02779. 3 interactions.
    STRINGi 9606.ENSP00000253055.

    Chemistry

    BindingDBi Q02779.
    ChEMBLi CHEMBL2873.
    GuidetoPHARMACOLOGYi 2070.

    PTM databases

    PhosphoSitei Q02779.

    Polymorphism databases

    DMDMi 145559494.

    Proteomic databases

    PaxDbi Q02779.
    PRIDEi Q02779.

    Protocols and materials databases

    DNASUi 4294.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000253055 ; ENSP00000253055 ; ENSG00000130758 .
    GeneIDi 4294.
    KEGGi hsa:4294.
    UCSCi uc002ona.3. human.

    Organism-specific databases

    CTDi 4294.
    GeneCardsi GC19P040697.
    H-InvDB HIX0040140.
    HGNCi HGNC:6849. MAP3K10.
    HPAi HPA007039.
    MIMi 600137. gene.
    neXtProti NX_Q02779.
    PharmGKBi PA30593.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000060081.
    HOVERGENi HBG067662.
    InParanoidi Q02779.
    KOi K04418.
    OMAi KGHFKKS.
    OrthoDBi EOG7D85VN.
    PhylomeDBi Q02779.
    TreeFami TF105118.

    Enzyme and pathway databases

    SignaLinki Q02779.

    Miscellaneous databases

    ChiTaRSi MAP3K10. human.
    EvolutionaryTracei Q02779.
    GeneWikii MAP3K10.
    GenomeRNAii 4294.
    NextBioi 16901.
    PROi Q02779.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q02779.
    Bgeei Q02779.
    CleanExi HS_MAP3K10.
    Genevestigatori Q02779.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR015785. MAP3K10.
    IPR016231. MAPKKK9/10/11.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001452. SH3_domain.
    [Graphical view ]
    PANTHERi PTHR23257:SF370. PTHR23257:SF370. 1 hit.
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000556. MAPKKK9_11. 1 hit.
    PRINTSi PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00326. SH3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2."
      Dorow D.S., Devereux L., Tu G.F., Price G., Nicholl J.K., Sutherland G.R., Simpson R.J.
      Eur. J. Biochem. 234:492-500(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. "Cloning and characterization of MST, a novel (putative) serine/threonine kinase with SH3 domain."
      Katoh M., Hirai M., Sugimura T., Terada M.
      Oncogene 10:1447-1451(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    3. "Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains."
      Dorow D.S., Devereux L., Dietzsch E., de Kretser T.
      Eur. J. Biochem. 213:701-710(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-480.
      Tissue: Colon epithelium.
    4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498; SER-502 AND THR-558, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    5. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    6. "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: VARIANT [LARGE SCALE ANALYSIS] GLU-107.

    Entry informationi

    Entry nameiM3K10_HUMAN
    AccessioniPrimary (citable) accession number: Q02779
    Secondary accession number(s): Q12761, Q14871
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: April 17, 2007
    Last modified: October 1, 2014
    This is version 146 of the entry and version 3 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3