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Q9Y4K4

- M4K5_HUMAN

UniProt

Q9Y4K4 - M4K5_HUMAN

Protein

Mitogen-activated protein kinase kinase kinase kinase 5

Gene

MAP4K5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.1 Publication

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei49 – 491ATP1 PublicationPROSITE-ProRule annotation
    Active sitei140 – 1401Proton acceptorPROSITE-ProRule annotation

    Regions

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

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. protein kinase activity Source: ProtInc
    4. protein serine/threonine kinase activity Source: UniProtKB
    5. small GTPase regulator activity Source: InterPro

    GO - Biological processi

    1. activation of JUN kinase activity Source: ProtInc
    2. intracellular signal transduction Source: UniProtKB
    3. protein phosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ9Y4K4.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 5 (EC:2.7.11.1)
    Alternative name(s):
    Kinase homologous to SPS1/STE20
    Short name:
    KHS
    MAPK/ERK kinase kinase kinase 5
    Short name:
    MEK kinase kinase 5
    Short name:
    MEKKK 5
    Gene namesi
    Name:MAP4K5
    OrganismiHomo sapiens (Human)Imported
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:6867. MAP4K5.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. plasma membrane Source: HPA

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi49 – 491K → R: Loss of kinase activity and ability to activate JNK family. 1 Publication

    Organism-specific databases

    PharmGKBiPA30613.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 846846Mitogen-activated protein kinase kinase kinase kinase 5PRO_0000086282Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei335 – 3351PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9Y4K4.
    PaxDbiQ9Y4K4.
    PRIDEiQ9Y4K4.

    PTM databases

    PhosphoSiteiQ9Y4K4.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed in all tissues examined, with high levels in the ovary, testis and prostate.1 Publication

    Gene expression databases

    ArrayExpressiQ9Y4K4.
    BgeeiQ9Y4K4.
    CleanExiHS_MAP4K5.
    GenevestigatoriQ9Y4K4.

    Organism-specific databases

    HPAiHPA036696.

    Interactioni

    Subunit structurei

    Interacts with both SH3 domains of the adapter proteins CRK and CRKL.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CRKP461085EBI-1279,EBI-886
    GRB2P629934EBI-1279,EBI-401755
    NCK1P163332EBI-1279,EBI-389883

    Protein-protein interaction databases

    BioGridi116353. 11 interactions.
    IntActiQ9Y4K4. 9 interactions.
    MINTiMINT-7241969.
    STRINGi9606.ENSP00000414032.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Y4K4.
    SMRiQ9Y4K4. Positions 13-346.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini20 – 277258Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini506 – 819314CNHPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 CNH domain.CuratedPROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000230824.
    HOVERGENiHBG036702.
    InParanoidiQ9Y4K4.
    KOiK08833.
    OrthoDBiEOG7WX07M.
    PhylomeDBiQ9Y4K4.
    TreeFamiTF105121.

    Family and domain databases

    InterProiIPR001180. Citron.
    IPR011009. Kinase-like_dom.
    IPR021160. MAPKKKK.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    [Graphical view]
    PfamiPF00780. CNH. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038172. MAPKKKK. 1 hit.
    SMARTiSM00036. CNH. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50219. CNH. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Y4K4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEAPLRPAAD ILRRNPQQDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI    50
    IKLEPGDDFS LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG 100
    SLQDIYHVTG PLSELQIAYV CRETLQGLAY LHTKGKMHRD IKGANILLTD 150
    HGDVKLADFG VAAKITATIA KRKSFIGTPY WMAPEVAAVE KNGGYNQLCD 200
    IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL KDKTKWSSTF 250
    HNFVKIALTK NPKKRPTAER LLTHTFVAQP GLSRALAVEL LDKVNNPDNH 300
    AHYTEADDDD FEPHAIIRHT IRSTNRNARA ERTASEINFD KLQFEPPLRK 350
    ETEARDEMGL SSDPNFMLQW NPFVDGANTG KSTSKRAIPP PLPPKPRISS 400
    YPEDNFPDEE KASTIKHCPD SESRAPQILR RQSSPSCGPV AETSSIGNGD 450
    GISKLMSENT EGSAQAPQLP RKNDKRDFPK PAINGLPPTP KVLMGACFSK 500
    VFDGCPLKIN CATSWIHPDT KDQYIIFGTE DGIYTLNLNE LHEATMEQLF 550
    PRKCTWLYVI NNTLMSLSEG KTFQLYSHNL IALFEHAKKP GLAAHIQTHR 600
    FPDRILPRKF ALTTKIPDTK GCHKCCIVRN PYTGHKYLCG ALQSGIVLLQ 650
    WYEPMQKFML IKHFDFPLPS PLNVFEMLVI PEQEYPMVCV AISKGTESNQ 700
    VVQFETINLN SASSWFTEIG AGSQQLDSIH VTQLERDTVL VCLDKFVKIV 750
    NLQGKLKSSK KLASELSFDF RIESVVCLQD SVLAFWKHGM QGKSFKSDEV 800
    TQEISDETRV FRLLGSDRVV VLESRPTENP TAHSNLYILA GHENSY 846
    Length:846
    Mass (Da):95,040
    Last modified:November 1, 1999 - v1
    Checksum:iB17F95196AA14E08
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411H → Y.
    Corresponds to variant rs34726242 [ dbSNP | Ensembl ].
    VAR_057102
    Natural varianti334 – 3341A → T.1 Publication
    Corresponds to variant rs12881869 [ dbSNP | Ensembl ].
    VAR_040747
    Natural varianti407 – 4071P → L.1 Publication
    Corresponds to variant rs34818002 [ dbSNP | Ensembl ].
    VAR_040748
    Natural varianti446 – 4461I → V.1 Publication
    Corresponds to variant rs55815015 [ dbSNP | Ensembl ].
    VAR_040749
    Natural varianti473 – 4731N → K.2 Publications
    Corresponds to variant rs35768475 [ dbSNP | Ensembl ].
    VAR_040750
    Natural varianti552 – 5521R → Q.1 Publication
    Corresponds to variant rs55997280 [ dbSNP | Ensembl ].
    VAR_040751
    Natural varianti633 – 6331T → M.1 Publication
    Corresponds to variant rs17780143 [ dbSNP | Ensembl ].
    VAR_040752

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77129 mRNA. Translation: AAB48435.1.
    BC036013 mRNA. Translation: AAH36013.1.
    RefSeqiNP_006566.2. NM_006575.4.
    NP_942089.1. NM_198794.2.
    XP_006720076.1. XM_006720013.1.
    UniGeneiHs.130491.

    Genome annotation databases

    EnsembliENST00000013125; ENSP00000013125; ENSG00000012983.
    GeneIDi11183.
    KEGGihsa:11183.
    UCSCiuc001wya.3. human.

    Polymorphism databases

    DMDMi30316147.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77129 mRNA. Translation: AAB48435.1 .
    BC036013 mRNA. Translation: AAH36013.1 .
    RefSeqi NP_006566.2. NM_006575.4.
    NP_942089.1. NM_198794.2.
    XP_006720076.1. XM_006720013.1.
    UniGenei Hs.130491.

    3D structure databases

    ProteinModelPortali Q9Y4K4.
    SMRi Q9Y4K4. Positions 13-346.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116353. 11 interactions.
    IntActi Q9Y4K4. 9 interactions.
    MINTi MINT-7241969.
    STRINGi 9606.ENSP00000414032.

    Chemistry

    BindingDBi Q9Y4K4.
    ChEMBLi CHEMBL4852.
    GuidetoPHARMACOLOGYi 2089.

    PTM databases

    PhosphoSitei Q9Y4K4.

    Polymorphism databases

    DMDMi 30316147.

    Proteomic databases

    MaxQBi Q9Y4K4.
    PaxDbi Q9Y4K4.
    PRIDEi Q9Y4K4.

    Protocols and materials databases

    DNASUi 11183.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000013125 ; ENSP00000013125 ; ENSG00000012983 .
    GeneIDi 11183.
    KEGGi hsa:11183.
    UCSCi uc001wya.3. human.

    Organism-specific databases

    CTDi 11183.
    GeneCardsi GC14M050885.
    HGNCi HGNC:6867. MAP4K5.
    HPAi HPA036696.
    MIMi 604923. gene.
    neXtProti NX_Q9Y4K4.
    PharmGKBi PA30613.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000230824.
    HOVERGENi HBG036702.
    InParanoidi Q9Y4K4.
    KOi K08833.
    OrthoDBi EOG7WX07M.
    PhylomeDBi Q9Y4K4.
    TreeFami TF105121.

    Enzyme and pathway databases

    SignaLinki Q9Y4K4.

    Miscellaneous databases

    ChiTaRSi MAP4K5. human.
    GeneWikii MAP4K5.
    GenomeRNAii 11183.
    NextBioi 42555.
    PROi Q9Y4K4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y4K4.
    Bgeei Q9Y4K4.
    CleanExi HS_MAP4K5.
    Genevestigatori Q9Y4K4.

    Family and domain databases

    InterProi IPR001180. Citron.
    IPR011009. Kinase-like_dom.
    IPR021160. MAPKKKK.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    [Graphical view ]
    Pfami PF00780. CNH. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038172. MAPKKKK. 1 hit.
    SMARTi SM00036. CNH. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50219. CNH. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel human SPS1/STE20 homologue, KHS, activates jun N-terminal kinase."
      Tung R.M., Blenis J.
      Oncogene 14:653-659(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-49.
      Tissue: T-cell.
    2. "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 LYS-473.
      Tissue: Testis.
    3. "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins."
      Oehrl W., Kardinal C., Ruf S., Adermann K., Groffen J., Feng G.-S., Blenis J., Tan T.-H., Feller S.M.
      Oncogene 17:1893-1901(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CRK AND CRKL.
    4. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    5. "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] THR-334; LEU-407; VAL-446; LYS-473; GLN-552 AND MET-633.

    Entry informationi

    Entry nameiM4K5_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y4K4
    Secondary accession number(s): Q8IYF6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 30, 2003
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 127 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 14
      Human chromosome 14: 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