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Q8IVH8

- M4K3_HUMAN

UniProt

Q8IVH8 - M4K3_HUMAN

Protein

Mitogen-activated protein kinase kinase kinase kinase 3

Gene

MAP4K3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      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 sitei45 – 451ATPPROSITE-ProRule annotation
    Binding sitei48 – 481ATP1 PublicationPROSITE-ProRule annotation
    Active sitei136 – 1361Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi22 – 309ATPPROSITE-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. intracellular signal transduction Source: UniProtKB
    2. JNK cascade Source: ProtInc
    3. protein phosphorylation Source: UniProtKB
    4. response to tumor necrosis factor Source: UniProtKB
    5. response to UV Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ8IVH8.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 3 (EC:2.7.11.1)
    Alternative name(s):
    Germinal center kinase-related protein kinase
    Short name:
    GLK
    MAPK/ERK kinase kinase kinase 3
    Short name:
    MEK kinase kinase 3
    Short name:
    MEKKK 3
    Gene namesi
    Name:MAP4K3
    Synonyms:RAB8IPL1
    OrganismiHomo sapiens (Human)Imported
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:6865. MAP4K3.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi48 – 481K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication

    Organism-specific databases

    PharmGKBiPA30611.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 894894Mitogen-activated protein kinase kinase kinase kinase 3PRO_0000086277Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine2 Publications
    Modified residuei398 – 3981Phosphoserine1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ8IVH8.
    PaxDbiQ8IVH8.
    PRIDEiQ8IVH8.

    PTM databases

    PhosphoSiteiQ8IVH8.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.1 Publication

    Gene expression databases

    ArrayExpressiQ8IVH8.
    BgeeiQ8IVH8.
    CleanExiHS_MAP4K3.
    GenevestigatoriQ8IVH8.

    Organism-specific databases

    HPAiHPA030380.

    Interactioni

    Subunit structurei

    Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GRB2P629932EBI-1758170,EBI-401755
    LCP2Q130945EBI-1758170,EBI-346946
    PRKCQQ047594EBI-1758170,EBI-374762
    PrkcqQ021114EBI-1758170,EBI-2639157From a different organism.

    Protein-protein interaction databases

    BioGridi114063. 6 interactions.
    DIPiDIP-48924N.
    IntActiQ8IVH8. 10 interactions.
    STRINGi9606.ENSP00000263881.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IVH8.
    SMRiQ8IVH8. Positions 8-313.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 273258Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini556 – 867312CNHPROSITE-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.
    InParanoidiQ8IVH8.
    KOiK04406.
    OMAiQNEHRGT.
    OrthoDBiEOG7WX07M.
    PhylomeDBiQ8IVH8.
    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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 11 PublicationCurated (identifier: Q8IVH8-1) [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

    MNPGFDLSRR NPQEDFELIQ RIGSGTYGDV YKARNVNTGE LAAIKVIKLE    50
    PGEDFAVVQQ EIIMMKDCKH PNIVAYFGSY LRRDKLWICM EFCGGGSLQD 100
    IYHVTGPLSE LQIAYVSRET LQGLYYLHSK GKMHRDIKGA NILLTDNGHV 150
    KLADFGVSAQ ITATIAKRKS FIGTPYWMAP EVAAVERKGG YNQLCDLWAV 200
    GITAIELAEL QPPMFDLHPM RALFLMTKSN FQPPKLKDKM KWSNSFHHFV 250
    KMALTKNPKK RPTAEKLLQH PFVTQHLTRS LAIELLDKVN NPDHSTYHDF 300
    DDDDPEPLVA VPHRIHSTSR NVREEKTRSE ITFGQVKFDP PLRKETEPHH 350
    ELPDSDGFLD SSEEIYYTAR SNLDLQLEYG QGHQGGYFLG ANKSLLKSVE 400
    EELHQRGHVA HLEDDEGDDD ESKHSTLKAK IPPPLPPKPK SIFIPQEMHS 450
    TEDENQGTIK RCPMSGSPAK PSQVPPRPPP PRLPPHKPVA LGNGMSSFQL 500
    NGERDGSLCQ QQNEHRGTNL SRKEKKDVPK PISNGLPPTP KVHMGACFSK 550
    VFNGCPLKIH CASSWINPDT RDQYLIFGAE EGIYTLNLNE LHETSMEQLF 600
    PRRCTWLYVM NNCLLSISGK ASQLYSHNLP GLFDYARQMQ KLPVAIPAHK 650
    LPDRILPRKF SVSAKIPETK WCQKCCVVRN PYTGHKYLCG ALQTSIVLLE 700
    WVEPMQKFML IKHIDFPIPC PLRMFEMLVV PEQEYPLVCV GVSRGRDFNQ 750
    VVRFETVNPN STSSWFTESD TPQTNVTHVT QLERDTILVC LDCCIKIVNL 800
    QGRLKSSRKL SSELTFDFQI ESIVCLQDSV LAFWKHGMQG RSFRSNEVTQ 850
    EISDSTRIFR LLGSDRVVVL ESRPTDNPTA NSNLYILAGH ENSY 894

    Note: No experimental confirmation available.

    Length:894
    Mass (Da):101,316
    Last modified:March 1, 2003 - v1
    Checksum:i6EB77BBB34E5B733
    GO
    Isoform 21 PublicationCurated (identifier: Q8IVH8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-12: MNPGFDLSRRNP → MA

    Show »
    Length:884
    Mass (Da):100,133
    Checksum:i14839222F5360166
    GO
    Isoform 31 PublicationCurated (identifier: Q8IVH8-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         352-372: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:873
    Mass (Da):98,954
    Checksum:i0C7D648387CFFE0C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti392 – 3921N → D in AAC15472. (PubMed:9275185)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti200 – 2001V → L.1 Publication
    Corresponds to variant rs35957290 [ dbSNP | Ensembl ].
    VAR_040743
    Natural varianti424 – 4241H → Q.1 Publication
    Corresponds to variant rs56317466 [ dbSNP | Ensembl ].
    VAR_040744
    Natural varianti669 – 6691T → S in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
    VAR_040745

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1212MNPGF…SRRNP → MA in isoform 2. 1 PublicationVSP_007052Add
    BLAST
    Alternative sequencei352 – 37221Missing in isoform 3. 1 PublicationVSP_007053Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF000145 mRNA. Translation: AAC15472.1.
    AF445413
    , AF445385, AF445386, AF445387, AF445388, AF445390, AF445391, AF445392, AF445393, AF445394, AF445395, AF445396, AF445397, AF445398, AF445399, AF445400, AF445401, AF445402, AF445403, AF445404, AF445405, AF445406, AF445407, AF445408, AF445409, AF445410, AF445411, AF445412 Genomic DNA. Translation: AAN75849.1.
    AF445413
    , AF445385, AF445386, AF445387, AF445388, AF445390, AF445391, AF445392, AF445393, AF445394, AF445395, AF445397, AF445398, AF445399, AF445400, AF445401, AF445402, AF445403, AF445404, AF445405, AF445406, AF445407, AF445408, AF445409, AF445410, AF445411, AF445412 Genomic DNA. Translation: AAN75850.1.
    CH471053 Genomic DNA. Translation: EAX00346.1.
    BC071579 mRNA. Translation: AAH71579.1.
    AC007684 Genomic DNA. Translation: AAF19240.1.
    CCDSiCCDS1803.1. [Q8IVH8-1]
    CCDS58707.1. [Q8IVH8-3]
    RefSeqiNP_001257354.1. NM_001270425.1. [Q8IVH8-3]
    NP_003609.2. NM_003618.3. [Q8IVH8-1]
    UniGeneiHs.655750.

    Genome annotation databases

    EnsembliENST00000263881; ENSP00000263881; ENSG00000011566. [Q8IVH8-1]
    ENST00000341681; ENSP00000345434; ENSG00000011566. [Q8IVH8-3]
    GeneIDi8491.
    KEGGihsa:8491.
    UCSCiuc002rro.4. human. [Q8IVH8-1]
    uc002rrp.4. human. [Q8IVH8-3]

    Polymorphism databases

    DMDMi29427817.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF000145 mRNA. Translation: AAC15472.1 .
    AF445413
    , AF445385 , AF445386 , AF445387 , AF445388 , AF445390 , AF445391 , AF445392 , AF445393 , AF445394 , AF445395 , AF445396 , AF445397 , AF445398 , AF445399 , AF445400 , AF445401 , AF445402 , AF445403 , AF445404 , AF445405 , AF445406 , AF445407 , AF445408 , AF445409 , AF445410 , AF445411 , AF445412 Genomic DNA. Translation: AAN75849.1 .
    AF445413
    , AF445385 , AF445386 , AF445387 , AF445388 , AF445390 , AF445391 , AF445392 , AF445393 , AF445394 , AF445395 , AF445397 , AF445398 , AF445399 , AF445400 , AF445401 , AF445402 , AF445403 , AF445404 , AF445405 , AF445406 , AF445407 , AF445408 , AF445409 , AF445410 , AF445411 , AF445412 Genomic DNA. Translation: AAN75850.1 .
    CH471053 Genomic DNA. Translation: EAX00346.1 .
    BC071579 mRNA. Translation: AAH71579.1 .
    AC007684 Genomic DNA. Translation: AAF19240.1 .
    CCDSi CCDS1803.1. [Q8IVH8-1 ]
    CCDS58707.1. [Q8IVH8-3 ]
    RefSeqi NP_001257354.1. NM_001270425.1. [Q8IVH8-3 ]
    NP_003609.2. NM_003618.3. [Q8IVH8-1 ]
    UniGenei Hs.655750.

    3D structure databases

    ProteinModelPortali Q8IVH8.
    SMRi Q8IVH8. Positions 8-313.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114063. 6 interactions.
    DIPi DIP-48924N.
    IntActi Q8IVH8. 10 interactions.
    STRINGi 9606.ENSP00000263881.

    Chemistry

    BindingDBi Q8IVH8.
    ChEMBLi CHEMBL5432.
    GuidetoPHARMACOLOGYi 2087.

    PTM databases

    PhosphoSitei Q8IVH8.

    Polymorphism databases

    DMDMi 29427817.

    Proteomic databases

    MaxQBi Q8IVH8.
    PaxDbi Q8IVH8.
    PRIDEi Q8IVH8.

    Protocols and materials databases

    DNASUi 8491.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000263881 ; ENSP00000263881 ; ENSG00000011566 . [Q8IVH8-1 ]
    ENST00000341681 ; ENSP00000345434 ; ENSG00000011566 . [Q8IVH8-3 ]
    GeneIDi 8491.
    KEGGi hsa:8491.
    UCSCi uc002rro.4. human. [Q8IVH8-1 ]
    uc002rrp.4. human. [Q8IVH8-3 ]

    Organism-specific databases

    CTDi 8491.
    GeneCardsi GC02M039476.
    H-InvDB HIX0001996.
    HGNCi HGNC:6865. MAP4K3.
    HPAi HPA030380.
    MIMi 604921. gene.
    neXtProti NX_Q8IVH8.
    PharmGKBi PA30611.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000230824.
    HOVERGENi HBG036702.
    InParanoidi Q8IVH8.
    KOi K04406.
    OMAi QNEHRGT.
    OrthoDBi EOG7WX07M.
    PhylomeDBi Q8IVH8.
    TreeFami TF105121.

    Enzyme and pathway databases

    SignaLinki Q8IVH8.

    Miscellaneous databases

    ChiTaRSi MAP4K3. human.
    GenomeRNAii 8491.
    NextBioi 31767.
    PROi Q8IVH8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IVH8.
    Bgeei Q8IVH8.
    CleanExi HS_MAP4K3.
    Genevestigatori Q8IVH8.

    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. "Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase."
      Diener K., Wang X.S., Chen C., Meyer C.F., Keesler G., Zukowski M., Tan T.-H., Yao Z.
      Proc. Natl. Acad. Sci. U.S.A. 94:9687-9692(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-48.
      Tissue: Macrophage and Skeletal muscle.
    2. "Physical/genetic map of the 2p22-2p21 region on chromosome 2."
      Gorry M.C., Zhang Y., Marks J.J., Suppe B., Hart S., Cortelli J., Pallos D., Hart T.C.
      Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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: Testis.
    5. Edwards J., Wohldmann P., Hawkins M., Harkins R.
      Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE OF 1-712 (ISOFORM 1).
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "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] LEU-200; GLN-424 AND SER-669.

    Entry informationi

    Entry nameiM4K3_HUMAN
    AccessioniPrimary (citable) accession number: Q8IVH8
    Secondary accession number(s): Q6IQ39
    , Q8IVH7, Q9UDM5, Q9Y6R5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 28, 2003
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 119 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 2
      Human chromosome 2: 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