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

Gene ID: 4215, updated on 27-Nov-2024

Summary

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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; AllianceGenome:HGNC:6855
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
mouse all
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Genomic context

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See MAP3K3 in Genome Data Viewer
Location:
17q23.3
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (63622417..63696305)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (64493028..64567209)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (61699777..61773665)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:61687966-61688466 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:61688467-61688967 Neighboring gene translational activator of cytochrome c oxidase I Neighboring gene family with sequence similarity 136 member A pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8821 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8822 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8823 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8824 Neighboring gene eukaryotic translation elongation factor 1 delta pseudogene 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12550 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12551 Neighboring gene VISTA enhancer hs1856 Neighboring gene uncharacterized LOC101927898 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12552 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12553 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12554 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:61771715-61772602 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12555 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12556 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12558 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8826 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8827 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:61777898-61778483 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:61778484-61779068 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8829 Neighboring gene uncharacterized LOC729683 Neighboring gene LIM domain containing 2 Neighboring gene Sharpr-MPRA regulatory region 9817 Neighboring gene STE20 related adaptor alpha Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:61817285-61817784 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8830

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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 Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. MiroRNA-188 Acts as Tumor Suppressor in Non-Small-Cell Lung Cancer by Targeting MAP3K3. Zhao L, et al. Mol Pharm, 2018 Apr 2. PMID 29528232
  2. Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative. Ellinger-Ziegelbauer H, et al. J Biol Chem, 1997 Jan 31. PMID 9006902
  3. The expression and role of MEKK3 in renal clear cell carcinoma. Lu H, et al. Anat Rec (Hoboken), 2015 Apr. PMID 25388155
  4. Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis. Hasan R, et al. BMC Cancer, 2014 Jan 2. PMID 24383423, Free PMC Article
  5. Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure. Hu Q, et al. Biochemistry, 2007 Nov 27. PMID 17985933

See all (114) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations.
    Title: Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations.
  2. Circ_0006988 promotes the proliferation, metastasis and angiogenesis of non-small cell lung cancer cells by modulating miR-491-5p/MAP3K3 axis.
    Title: Circ_0006988 promotes the proliferation, metastasis and angiogenesis of non-small cell lung cancer cells by modulating miR-491-5p/MAP3K3 axis.
  3. Somatic MAP3K3 and PIK3CA mutations in sporadic cerebral and spinal cord cavernous malformations.
    Title: Somatic MAP3K3 and PIK3CA mutations in sporadic cerebral and spinal cord cavernous malformations.
  4. MEKK3 activates IRF7 to trigger a potent type I interferon induction in response to TLR7/9 signaling.
    Title: MEKK3 activates IRF7 to trigger a potent type I interferon induction in response to TLR7/9 signaling.
  5. Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation.
    Title: Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation.
  6. Overexpression of MAP3K3 promotes tumour growth through activation of the NF-kappaB signalling pathway in ovarian carcinoma.
    Title: Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma.
  7. This study suggests that expression of miR-194 is down-regulated in nasopharyngeal carcinoma, and that miR-194 can directly target MAP3K3 to regulate tumor progression. Given the pivotal involvement of MAP3K3 in nasopharyngeal carcinoma development, targeting miR-194 may be a novel strategy for the treatment of nasopharyngeal carcinoma.
    Title: MiR-194 regulates nasopharyngeal carcinoma progression by modulating MAP3K3 expression.
  8. MEKK3 overexpression prevented the inhibitory effects of miR9 on the viability, migration and invasion of PC cells.
    Title: MicroRNA‑9 suppresses human prostate cancer cell viability, invasion and migration via modulation of mitogen‑activated protein kinase kinase kinase 3 expression.
  9. the data revealed the novel role and target of miR505 in NSCLC cells, which may provide novel insights regarding its role in the carcinogenesis of NSCLC and its potential values for clinical applications.
    Title: miR‑505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT‑NFκB pathway in NSCLC cells.
  10. Its downstream target MAP3K3 could be a potential therapeutic target for NSCLC.
    Title: MiroRNA-188 Acts as Tumor Suppressor in Non-Small-Cell Lung Cancer by Targeting MAP3K3.
Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe).
EBI GWAS Catalog
Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
EBI GWAS Catalog
Many sequence variants affecting diversity of adult human height.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables JUN kinase kinase kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables MAP kinase kinase kinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in MAPK cascade TAS
Traceable Author Statement
more info
 PubMed 
involved_in blood vessel development IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within intracellular signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of canonical NF-kappaB signal transduction IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in positive regulation of p38MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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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_001350697.1
NP_002392.2
NP_976226.1
XP_005257435.1
XP_047292040.1
XP_047292041.1
XP_047292042.1
XP_047292043.1
XP_047292044.1
XP_054172127.1
XP_054172128.1
XP_054172129.1
XP_054172130.1
XP_054172131.1
XP_054172132.1

NCBI Reference Sequences (RefSeq)

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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_001330431.2 → NP_001317360.1  mitogen-activated protein kinase kinase kinase 3 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC046185, AK225784, BC008336, BC143224, BE396317, BU633068, CN281110
    Consensus CDS
    CCDS82186.1
    UniProtKB/TrEMBL
    J3KRN4, Q1PBM3
    Related
    ENSP00000462086.1, ENST00000577395.5
    Conserved Domains (2) summary
    cd06405
    Location:45 → 123
    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:357 → 617
    STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

  2. NM_001363768.2 → NP_001350697.1  mitogen-activated protein kinase kinase kinase 3 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC046185, AK225784
    Consensus CDS
    CCDS86624.1
    UniProtKB/TrEMBL
    J3QRB6, Q1PBM3
    Related
    ENSP00000464130.1, ENST00000584573.5
    Conserved Domains (2) summary
    cd06405
    Location:76 → 154
    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:388 → 648
    STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

  3. NM_002401.5 → NP_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
    B2RCW2, D3DU15, Q5BKZ6, Q8N3I9, Q99759
    UniProtKB/TrEMBL
    Q1PBM3
    Related
    ENSP00000354485.4, ENST00000361733.8
    Conserved Domains (2) summary
    cd06405
    Location:45 → 123
    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:361 → 621
    STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

  4. NM_203351.3 → NP_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/TrEMBL
    Q1PBM3
    Related
    ENSP00000354927.3, ENST00000361357.7
    Conserved Domains (2) summary
    cd06405
    Location:76 → 154
    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:392 → 652
    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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    63622417..63696305
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005257378.3 → XP_005257435.1  mitogen-activated protein kinase kinase kinase 3 isoform X1

    Conserved Domains (2) summary
    cd06405
    Location:76 → 154
    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) ...
    cl21453
    Location:392 → 524
    PKc_like; Protein Kinases, catalytic domain

  2. XM_047436084.1 → XP_047292040.1  mitogen-activated protein kinase kinase kinase 3 isoform X2

  3. XM_047436085.1 → XP_047292041.1  mitogen-activated protein kinase kinase kinase 3 isoform X3

  4. XM_047436086.1 → XP_047292042.1  mitogen-activated protein kinase kinase kinase 3 isoform X4

  5. XM_047436087.1 → XP_047292043.1  mitogen-activated protein kinase kinase kinase 3 isoform X5

  6. XM_047436088.1 → XP_047292044.1  mitogen-activated protein kinase kinase kinase 3 isoform X6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    64493028..64567209
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054316152.1 → XP_054172127.1  mitogen-activated protein kinase kinase kinase 3 isoform X1

  2. XM_054316153.1 → XP_054172128.1  mitogen-activated protein kinase kinase kinase 3 isoform X2

  3. XM_054316154.1 → XP_054172129.1  mitogen-activated protein kinase kinase kinase 3 isoform X3

  4. XM_054316155.1 → XP_054172130.1  mitogen-activated protein kinase kinase kinase 3 isoform X4

  5. XM_054316156.1 → XP_054172131.1  mitogen-activated protein kinase kinase kinase 3 isoform X5

  6. XM_054316157.1 → XP_054172132.1  mitogen-activated protein kinase kinase kinase 3 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99759.2 GenPept UniProtKB/Swiss-Prot:Q99759

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