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

Gene ID: 4215, updated on 12-Aug-2018

Summary

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]
Expression
Ubiquitous expression in spleen (RPKM 15.4), lung (RPKM 14.5) and 25 other tissues See more
Orthologs

Genomic context

See MAP3K3 in Genome Data Viewer
Location:
17q23.3
Exon count:
17
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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 VISTA enhancer hs1856 Neighboring gene uncharacterized LOC101927898 Neighboring gene uncharacterized LOC729683 Neighboring gene LIM domain containing 2 Neighboring gene STE20-related kinase adaptor alpha

Genomic regions, transcripts, and products

Expression

  • 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

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

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

Pathways from BioSystems

  • Angiopoietin Like Protein 8 Regulatory Pathway, organism-specific biosystem (from WikiPathways)
    Angiopoietin Like Protein 8 Regulatory Pathway, organism-specific biosystemThe hepatic ANGPTL8 (Angiopoietin Like Protein 8) regulatory pathway represents an up-to-date curated interactive pathway for all of the interactions from the known regulators of ANGPTL8 and updated ...
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • EBV LMP1 signaling, organism-specific biosystem (from WikiPathways)
    EBV LMP1 signaling, organism-specific biosystem
    EBV LMP1 signaling
  • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
    EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
  • GnRH signaling pathway, organism-specific biosystem (from KEGG)
    GnRH signaling pathway, organism-specific biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...
  • GnRH signaling pathway, conserved biosystem (from KEGG)
    GnRH signaling pathway, conserved biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...
  • HTLV-I infection, organism-specific biosystem (from KEGG)
    HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • HTLV-I infection, conserved biosystem (from KEGG)
    HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • IL-1 signaling pathway, organism-specific biosystem (from WikiPathways)
    IL-1 signaling pathway, organism-specific biosystemThe IL-1 family of cytokines currently consists of 11 members which are encoded by distinct genes and includes IL-1?, IL-1?, and the IL-1 Receptor antagonist (IL-1RA). The major role of IL-1 type cyt...
  • IL1-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL1-mediated signaling events, organism-specific biosystem
    IL1-mediated signaling events
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Insulin Signaling, organism-specific biosystem (from WikiPathways)
    Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...
  • Interleukin-1 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-1 signaling, organism-specific biosystemInterleukin 1 (IL1) signals via Interleukin 1 receptor 1 (IL1R1), the only signaling-capable IL1 receptor. This is a single chain type 1 transmembrane protein comprising an extracellular ligand bindi...
  • MAPK (ERK5) signaling, organism-specific biosystem (from KEGG)
    MAPK (ERK5) signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • MAPK (ERK5) signaling, conserved biosystem (from KEGG)
    MAPK (ERK5) signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • MAPK (JNK) signaling, organism-specific biosystem (from KEGG)
    MAPK (JNK) signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • MAPK (JNK) signaling, conserved biosystem (from KEGG)
    MAPK (JNK) signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • MAPK (p38) signaling, organism-specific biosystem (from KEGG)
    MAPK (p38) signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • MAPK (p38) signaling, conserved biosystem (from KEGG)
    MAPK (p38) signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • MAPK Cascade, organism-specific biosystem (from WikiPathways)
    MAPK Cascade, organism-specific biosystem
    MAPK Cascade
  • MAPK signaling pathway, organism-specific biosystem (from KEGG)
    MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
  • MAPK signaling pathway, conserved biosystem (from KEGG)
    MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
  • Neurotrophin signaling pathway, organism-specific biosystem (from KEGG)
    Neurotrophin signaling pathway, organism-specific biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
  • Neurotrophin signaling pathway, conserved biosystem (from KEGG)
    Neurotrophin signaling pathway, conserved biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
  • Regulation of p38-alpha and p38-beta, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of p38-alpha and p38-beta, organism-specific biosystem
    Regulation of p38-alpha and p38-beta
  • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
    Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
  • Structural Pathway of Interleukin 1 (IL-1), organism-specific biosystem (from WikiPathways)
    Structural Pathway of Interleukin 1 (IL-1), organism-specific biosystemPathway published in http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003470 IL-1 signaling pathway reconstructed by combining related pathways and information from the litera...
  • TNF alpha Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TNF alpha Signaling Pathway, organism-specific biosystemTumor necrosis factor alpha (TNF?) is a proinflammatory cytokine involved in various biological processes including regulation of cell proliferation, differentiation, apoptosis and immune response. T...
  • TNF receptor signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    TNF receptor signaling pathway, organism-specific biosystem
    TNF receptor signaling pathway
  • p38 MAPK signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    p38 MAPK signaling pathway, organism-specific biosystem
    p38 MAPK signaling pathway

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 
protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
MAPK cascade TAS
Traceable Author Statement
more info
PubMed 
activation of MAPKK activity IEA
Inferred from Electronic Annotation
more info
 
activation of protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
blood vessel development IEA
Inferred from Electronic Annotation
more info
 
interleukin-1-mediated signaling pathway TAS
Traceable Author Statement
more info
 
intracellular signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cellular senescence IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
Inferred from Expression Pattern
more info
PubMed 
positive regulation of cell migration involved in sprouting angiogenesis IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of cell proliferation in bone marrow IMP
Inferred from Mutant Phenotype
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 
signal transduction by protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
stress-activated protein kinase signaling cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 

General protein information

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_001317360.1
NP_002392.2
NP_976226.1
XP_005257433.1
XP_005257435.1

NCBI Reference Sequences (RefSeq)

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
    Related
    ENSP00000462086.1, ENST00000577395.5
    Conserved Domains (2) 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) ...
    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_001363768.1NP_001350697.1  mitogen-activated protein kinase kinase kinase 3 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC046185, AK225784
    Consensus CDS
    CCDS86624.1
    Conserved Domains (2) 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) ...
    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
  3. NM_002401.4NP_002392.2  mitogen-activated protein kinase kinase kinase 3 isoform 2

    See identical proteins and their annotated locations for NP_002392.2

    Status: REVIEWED

    Source sequence(s)
    AC046185, AL834303, BM728104, BM800091, BQ643432, BU633068
    Consensus CDS
    CCDS32702.1
    UniProtKB/Swiss-Prot
    Q99759
    Related
    ENSP00000354485.3, OTTHUMP00000260292, ENST00000361733.7
    Conserved Domains (2) 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) ...
    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
  4. NM_203351.2NP_976226.1  mitogen-activated protein kinase kinase kinase 3 isoform 1

    See identical proteins and their annotated locations for NP_976226.1

    Status: REVIEWED

    Source sequence(s)
    AC046185, AL834303
    Consensus CDS
    CCDS32701.1
    UniProtKB/Swiss-Prot
    Q99759
    Related
    ENSP00000354927.3, OTTHUMP00000260293, ENST00000361357.7
    Conserved Domains (2) 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) ...
    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 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p12 Primary Assembly

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

mRNA and Protein(s)

  1. XM_005257378.2XP_005257435.1  mitogen-activated protein kinase kinase kinase 3 isoform X2

    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
  2. XM_005257376.4XP_005257433.1  mitogen-activated protein kinase kinase kinase 3 isoform X1

    UniProtKB/TrEMBL
    J3QRB6
    Related
    ENSP00000464130.1, OTTHUMP00000260291, ENST00000584573.5
    Conserved Domains (2) 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) ...
    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

RNA

  1. XR_934463.1 RNA Sequence

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