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P70218

- M4K1_MOUSE

UniProt

P70218 - M4K1_MOUSE

Protein

Mitogen-activated protein kinase kinase kinase kinase 1

Gene

Map4k1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 1 (01 Feb 1997)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.1 Publication

    Catalytic activityi

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

    Cofactori

    Magnesium.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei46 – 461ATP1 PublicationPROSITE-ProRule annotation
    Active sitei137 – 1371Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi23 – 319ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. cell proliferation Source: UniProtKB
    2. intracellular signal transduction Source: UniProtKB
    3. peptidyl-serine phosphorylation Source: UniProtKB
    4. protein autophosphorylation Source: UniProtKB
    5. protein phosphorylation Source: UniProtKB
    6. response to stress Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 1 (EC:2.7.11.1)
    Alternative name(s):
    Hematopoietic progenitor kinase
    Short name:
    HPK
    MAPK/ERK kinase kinase kinase 1
    Short name:
    MEK kinase kinase 1
    Short name:
    MEKKK 1
    Gene namesi
    Name:Map4k1
    Synonyms:Hpk1
    OrganismiMus musculus (Mouse)Imported
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:1346882. Map4k1.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi46 – 461K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 827827Mitogen-activated protein kinase kinase kinase kinase 1PRO_0000086274Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei165 – 1651Phosphothreonine; by autocatalysisBy similarity
    Modified residuei171 – 1711Phosphoserine; by autocatalysisBy similarity
    Modified residuei175 – 1751Phosphothreonine; by autocatalysisBy similarity
    Modified residuei354 – 3541Phosphothreonine; by autocatalysisBy similarity
    Modified residuei403 – 4031PhosphoserineBy similarity
    Modified residuei405 – 4051PhosphoserineBy similarity
    Modified residuei419 – 4191PhosphoserineBy similarity
    Modified residuei592 – 5921PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylates: phosphorylation promotes ubiquitination by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.By similarity
    Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex following autophosphorylation, leading to its degradation by the proteasome.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP70218.
    PRIDEiP70218.

    PTM databases

    PhosphoSiteiP70218.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed in all tissues examined at embryonic stage E16.5 with high levels in lung, heart and fetal liver. In the neonate, expression is restricted to the tissues which undergo lineage decisions, lung, thymus, liver, kidney and brain. In the adult, expression is limited to hemopoietic organs, thymus, bone marrow, and spleen and to the testis.1 Publication

    Gene expression databases

    BgeeiP70218.
    GenevestigatoriP70218.

    Interactioni

    Subunit structurei

    Interacts with MAP3K1. Interacts with FBXW8 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MAP3K11Q165843EBI-2906801,EBI-49961From a different organism.

    Protein-protein interaction databases

    BioGridi204964. 4 interactions.
    DIPiDIP-42073N.
    IntActiP70218. 4 interactions.
    MINTiMINT-1176243.

    Structurei

    Secondary structure

    1
    827
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi473 – 4764

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1UTIX-ray1.50D465-480[»]
    ProteinModelPortaliP70218.
    SMRiP70218. Positions 9-332.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP70218.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini17 – 274258Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini501 – 806306CNHPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00690000101936.
    HOGENOMiHOG000230824.
    HOVERGENiHBG036702.
    InParanoidiP70218.
    KOiK04408.
    OMAiLQWYQPM.
    OrthoDBiEOG7WX07M.
    PhylomeDBiP70218.
    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.

    P70218-1 [UniParc]FASTAAdd to Basket

    « Hide

    MALVDPDIFN KDPREHYDLL QRLGGGTYGE VFKARDKVSK DLVALKMVKM    50
    EPDDDVATLQ KEILMLKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ 100
    DIYQVTGSLS ELQISYVCRE VLQGLAYLHS EKKIHRDIKG ANILINDCGE 150
    VKLADFGISA QIGATLARRL SFIGTPYWMA PEVAAVALKG GYNELCDIWS 200
    LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK SRWSSSFHNF 250
    VKVTLTKNSK KRPSATKMLS HQLVSQPGLN RGLILDLLDK MKNPGKGLPV 300
    DIEDEEPEPP PAIPRRIRST YRASSLGIPD ADCCRRQMEF QRPRCVDCRP 350
    QAETVRLYPP AHFGSTSPRS QLSDSDDDYD DVDIPAPSEN IPPPLPPKPK 400
    FRSPSDDGSG GIRDDGQLSP GVLVRCASGP PPRTPRPGPP PATCSPHLTA 450
    RSDPSLWNPA APEPGQPPLV PPRKEKMRGK MENEKRREKY PLLVKLFNGC 500
    PLQIHSTAAW THPSTKDQNL LLGAEEGIFI LNRNDQEATL EMIFPGRTTW 550
    LYCINNLLMS LSGKTPYLYS HSILGLLERK DGRTGSPIAH ISPHRLLARK 600
    NMVSSKIQDT KGCRACCVAE SASSGGPFLC GALETSVVLL QWYQPMNKFL 650
    LVRQVLFPLP TPLPVFTLLT TPGSELPAVC IGVSPGQAAK SVLFHTVRFG 700
    ALSCWLDDSS TEHKGPVQVI QVKEDMVMVL MDGSLKLVTP EGAPAPGLRT 750
    PEIPMTEAVE AVAMVEDRLE AFWKHGVQVW APGLKQPLQE LRDPTLTFRL 800
    LCSPRPVVVE TRPTDDPTAP SNLYIQE 827
    Length:827
    Mass (Da):91,535
    Last modified:February 1, 1997 - v1
    Checksum:i82341BE9D13036BA
    GO

    Sequence cautioni

    The sequence AAH05433.1 differs from that shown. Reason: Intron retention.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti411 – 4111G → V in AAH24832. (PubMed:15489334)Curated
    Sequence conflicti444 – 4441C → R in AAH05433. (PubMed:15489334)Curated
    Sequence conflicti444 – 4441C → R in AAH24832. (PubMed:15489334)Curated
    Sequence conflicti807 – 8071V → I in AAH24832. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y09010 mRNA. Translation: CAA70213.1.
    BC005433 mRNA. Translation: AAH05433.1. Sequence problems.
    BC024832 mRNA. Translation: AAH24832.1.
    CCDSiCCDS39865.1.
    RefSeqiNP_032305.2. NM_008279.2.
    UniGeneiMm.148278.

    Genome annotation databases

    EnsembliENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337.
    GeneIDi26411.
    KEGGimmu:26411.
    UCSCiuc009gam.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y09010 mRNA. Translation: CAA70213.1 .
    BC005433 mRNA. Translation: AAH05433.1 . Sequence problems.
    BC024832 mRNA. Translation: AAH24832.1 .
    CCDSi CCDS39865.1.
    RefSeqi NP_032305.2. NM_008279.2.
    UniGenei Mm.148278.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1UTI X-ray 1.50 D 465-480 [» ]
    ProteinModelPortali P70218.
    SMRi P70218. Positions 9-332.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204964. 4 interactions.
    DIPi DIP-42073N.
    IntActi P70218. 4 interactions.
    MINTi MINT-1176243.

    PTM databases

    PhosphoSitei P70218.

    Proteomic databases

    PaxDbi P70218.
    PRIDEi P70218.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000085835 ; ENSMUSP00000082995 ; ENSMUSG00000037337 .
    GeneIDi 26411.
    KEGGi mmu:26411.
    UCSCi uc009gam.1. mouse.

    Organism-specific databases

    CTDi 11184.
    MGIi MGI:1346882. Map4k1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00690000101936.
    HOGENOMi HOG000230824.
    HOVERGENi HBG036702.
    InParanoidi P70218.
    KOi K04408.
    OMAi LQWYQPM.
    OrthoDBi EOG7WX07M.
    PhylomeDBi P70218.
    TreeFami TF105121.

    Miscellaneous databases

    EvolutionaryTracei P70218.
    NextBioi 304401.
    PROi P70218.
    SOURCEi Search...

    Gene expression databases

    Bgeei P70218.
    Genevestigatori P70218.

    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. "HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway."
      Kiefer F., Tibbles L.A., Anafi M., Janssen A., Zanke B.W., Lassam N., Pawson T., Woodgett J.R., Iscove N.N.
      EMBO J. 15:7013-7025(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-46.
      Tissue: Pre-B 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].
      Tissue: Mammary gland.

    Entry informationi

    Entry nameiM4K1_MOUSE
    AccessioniPrimary (citable) accession number: P70218
    Secondary accession number(s): Q8R3R0, Q99K62
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 28, 2003
    Last sequence update: February 1, 1997
    Last modified: October 1, 2014
    This is version 123 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3