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    MAP3K3 mitogen-activated protein kinase kinase kinase 3 [ Homo sapiens (human) ]

    Gene ID: 4215, updated on 22-Apr-2017
    Official Symbol
    MAP3K3provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 3provided by HGNC
    Primary source
    HGNC:HGNC:6855
    See related
    Ensembl:ENSG00000198909 MIM:602539; Vega:OTTHUMG00000178905
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MEKK3; MAPKKK3
    Summary
    This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    17q23.3
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 17 NC_000017.11 (63622209..63696310)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (61699404..61773670)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene translational activator of cytochrome c oxidase I Neighboring gene family with sequence similarity 136 member A pseudogene Neighboring gene eukaryotic translation elongation factor 1 delta pseudogene 7 Neighboring gene uncharacterized LOC107984984 Neighboring gene uncharacterized LOC101927898 Neighboring gene uncharacterized LOC729683 Neighboring gene LIM domain containing 2 Neighboring gene STE20-related kinase adaptor alpha

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe).
    NHGRI GWA Catalog
    Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
    NHGRI GWA Catalog
    Many sequence variants affecting diversity of adult human height.
    NHGRI GWA Catalog
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    NHGRI GWA Catalog
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      MAPK Cascade, organism-specific biosystem
      MAPK Cascade
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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    MAP kinase kinase kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    signal transducer, downstream of receptor, with serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Process Evidence Code Pubs
    MAPK cascade TAS
    Traceable Author Statement
    more info
    PubMed 
    actin cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    activation of MAPKK activity IEA
    Inferred from Electronic Annotation
    more info
     
    blood vessel development IEA
    Inferred from Electronic Annotation
    more info
     
    intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    positive regulation of p38MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    mitogen-activated protein kinase kinase kinase 3
    Names
    MAP/ERK kinase kinase 3
    MAPK/ERK kinase kinase 3
    MEK kinase 3
    MEKK 3
    NP_002392.2
    NP_976226.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001330431.1NP_001317360.1  mitogen-activated protein kinase kinase kinase 3 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AK225784, BC008336, BC143224, BE396317, BU633068, CN281110
      Consensus CDS
      CCDS82186.1
      UniProtKB/TrEMBL
      J3KRN4, Q96HN9
      Conserved Domains (3) summary
      cd06405
      Location:45123
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      smart00220
      Location:358617
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06625
      Location:357617
      STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases
    2. NM_002401.3NP_002392.2  mitogen-activated protein kinase kinase kinase 3 isoform 2

      See identical proteins and their annotated locations for NP_002392.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1. The resulting isoform (2) lacks an internal region, as compared to isoform 1.
      Source sequence(s)
      AL834303, BM728104, BM800091, BQ643432, BU633068
      Consensus CDS
      CCDS32702.1
      UniProtKB/Swiss-Prot
      Q99759
      Related
      ENSP00000354485.3, OTTHUMP00000260292, ENST00000361733.7, OTTHUMT00000443867
      Conserved Domains (3) summary
      cd06405
      Location:45123
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      smart00220
      Location:362621
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06625
      Location:361621
      STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases
    3. NM_203351.1NP_976226.1  mitogen-activated protein kinase kinase kinase 3 isoform 1

      See identical proteins and their annotated locations for NP_976226.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL834303, BM479726, BM728104, BM800091, BU633068
      Consensus CDS
      CCDS32701.1
      UniProtKB/Swiss-Prot
      Q99759
      Related
      ENSP00000354927.3, OTTHUMP00000260293, ENST00000361357.7, OTTHUMT00000443868
      Conserved Domains (3) summary
      cd06405
      Location:76154
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      smart00220
      Location:393652
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06625
      Location:392652
      STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p7 Primary Assembly

      Range
      63622209..63696310
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005257376.3XP_005257433.1  mitogen-activated protein kinase kinase kinase 3 isoform X1

      See identical proteins and their annotated locations for XP_005257433.1

      UniProtKB/TrEMBL
      J3QRB6
      Related
      ENSP00000464130.1, OTTHUMP00000260291, ENST00000584573.5, OTTHUMT00000443866
      Conserved Domains (3) summary
      cd06405
      Location:76154
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      smart00220
      Location:389648
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06625
      Location:388648
      STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases
    2. XM_005257378.2XP_005257435.1  mitogen-activated protein kinase kinase kinase 3 isoform X3

      Conserved Domains (3) summary
      cd06405
      Location:76154
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      smart00220
      Location:393522
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:392524
      PKc_like; Protein Kinases, catalytic domain
    3. XM_005257377.3XP_005257434.1  mitogen-activated protein kinase kinase kinase 3 isoform X2

      Related
      ENSP00000462086.1, OTTHUMP00000260294, ENST00000577395.5, OTTHUMT00000443869
      Conserved Domains (3) summary
      cd06405
      Location:45123
      PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
      smart00220
      Location:358617
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06625
      Location:357617
      STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

    RNA

    1. XR_934463.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018928.2 Alternate CHM1_1.1

      Range
      61764216..61838082
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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