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MAP3K1 mitogen-activated protein kinase kinase kinase 1 [ Homo sapiens (human) ]

Gene ID: 4214, updated on 5-Mar-2024

Summary

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Official Symbol
MAP3K1provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 1provided by HGNC
Primary source
HGNC:HGNC:6848
See related
Ensembl:ENSG00000095015 MIM:600982; AllianceGenome:HGNC:6848
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
MEKK; MEKK1; SRXY6; MEKK 1; MAPKKK1
Summary
The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]
Expression
Ubiquitous expression in spleen (RPKM 8.6), skin (RPKM 8.4) and 25 other tissues See more
Orthologs
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Genomic context

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See MAP3K1 in Genome Data Viewer
Location:
5q11.2
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (56815549..56896152)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (57643875..57724397)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (56111376..56191979)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:55810478-55810978 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:55830028-55830580 Neighboring gene chromosome 5 putative open reading frame 67 Neighboring gene MPRA-validated peak5248 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22567 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22568 Neighboring gene VISTA enhancer hs1638 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:55933112-55933681 Neighboring gene Sharpr-MPRA regulatory region 489 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22570 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22571 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:56052539-56053040 Neighboring gene growth/differentiation factor 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22572 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:56112185-56113008 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16022 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16021 Neighboring gene Sharpr-MPRA regulatory region 15646 Neighboring gene NANOG hESC enhancer GRCh37_chr5:56121191-56121701 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_86205 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:56139908-56140150 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:56146868-56147047 Neighboring gene uncharacterized LOC124901214 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_86223 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:56178189-56179388 Neighboring gene uncharacterized LOC105378980 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_86245 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22573 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16024 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22574 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:56206084-56206905 Neighboring gene SET domain containing 9 Neighboring gene MIER family member 3

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. MAP3K1 rs889312 polymorphism and cancer prognosis: A systematic review and meta-analysis. Aziz MA, et al. Cancer Rep (Hoboken), 2023 Jan. PMID 36560873, Free PMC Article
  2. Sex-dependent associations between MAP3K1 gene polymorphisms and soy products with the gastric cancer risk in Korea: a case-control study. Kwak JH, et al. BMC Gastroenterol, 2022 Dec 12. PMID 36510163, Free PMC Article
  3. Identification of a novel MAP3K1 variant in a family with 46, XY DSD and partial growth hormone deficiency. Cheng Y, et al. Mol Med Rep, 2022 Nov. PMID 36102299, Free PMC Article
  4. Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review. Ostrer H. Sex Dev, 2022. PMID 35290982
  5. [Gonadal dysgenesis 46,XY DSD associated with variants in the MAP3K1 gene]. Kalinchenko NY, et al. Probl Endokrinol (Mosk), 2020 Dec 12. PMID 33481368

See all (194) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MAP3K1 expression is associated with progression and poor prognosis of hormone receptor-positive, HER2-negative early-stage breast cancer.
    Title: MAP3K1 expression is associated with progression and poor prognosis of hormone receptor-positive, HER2-negative early-stage breast cancer.
  2. Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.
    Title: Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.
  3. Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.
    Title: Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.
  4. MAP3K1 rs889312 polymorphism and cancer prognosis: A systematic review and meta-analysis.
    Title: MAP3K1 rs889312 polymorphism and cancer prognosis: A systematic review and meta-analysis.
  5. Sex-dependent associations between MAP3K1 gene polymorphisms and soy products with the gastric cancer risk in Korea: a case-control study.
    Title: Sex-dependent associations between MAP3K1 gene polymorphisms and soy products with the gastric cancer risk in Korea: a case-control study.
  6. Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review.
    Title: Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review.
  7. Identification of a novel MAP3K1 variant in a family with 46, XY DSD and partial growth hormone deficiency.
    Title: Identification of a novel MAP3K1 variant in a family with 46, XY DSD and partial growth hormone deficiency.
  8. MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.
    Title: MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.
  9. LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia.
    Title: LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia.
  10. RNA-binding protein IMP3 is a novel regulator of MEK1/ERK signaling pathway in the progression of colorectal Cancer through the stabilization of MEKK1 mRNA.
    Title: RNA-binding protein IMP3 is a novel regulator of MEK1/ERK signaling pathway in the progression of colorectal Cancer through the stabilization of MEKK1 mRNA.
Submit: New GeneRIF Correction See all GeneRIFs (95)

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

Associated conditions

Description Tests
46,XY sex reversal 6
MedGen: C3151064 OMIM: 613762 GeneReviews: Nonsyndromic Disorders of Testicular Development Overview
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Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2013-08-22)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2013-08-22)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.
EBI GWAS Catalog
A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).
EBI GWAS Catalog
Biological, clinical and population relevance of 95 loci for blood lipids.
EBI GWAS Catalog
Discovery and refinement of loci associated with lipid levels.
EBI GWAS Catalog
Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
EBI GWAS Catalog
Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.
EBI GWAS Catalog
Genome-wide association study identifies five new breast cancer susceptibility loci.
EBI GWAS Catalog
Genome-wide association study identifies novel breast cancer susceptibility loci.
EBI GWAS Catalog
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
EBI GWAS Catalog
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
EBI GWAS Catalog
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.
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)

Genotypes

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 MAP kinase kinase kinase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables MAP kinase kinase kinase activity TAS
Traceable Author Statement
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 kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity EXP
Inferred from Experiment
more info
 PubMed 
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
  
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in protein phosphorylation NAS
Non-traceable Author Statement
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 1
Names
MAP/ERK kinase kinase 1
MAPK/ERK kinase kinase 1
MEK kinase 1
mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
NP_005912.1
XP_047273174.1
XP_047273175.1
XP_047273176.1
XP_054208617.1
XP_054208618.1
XP_054208619.1
XP_054208620.1

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.

Genomic

  1. NG_031884.1 RefSeqGene

    Range
    5477..86080
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_005921.2 → NP_005912.1  mitogen-activated protein kinase kinase kinase 1

    See identical proteins and their annotated locations for NP_005912.1

    Status: REVIEWED

    Source sequence(s)
    AA602425, AC008937, AF042838, BU194120, DA889202
    Consensus CDS
    CCDS43318.1
    UniProtKB/Swiss-Prot
    Q13233
    Related
    ENSP00000382423.3, ENST00000399503.4
    Conserved Domains (2) summary
    smart00220
    Location:1243 → 1508
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd06630
    Location:1242 → 1509
    STKc_MEKK1; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    56815549..56896152
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047417218.1 → XP_047273174.1  mitogen-activated protein kinase kinase kinase 1 isoform X1

  2. XM_047417219.1 → XP_047273175.1  mitogen-activated protein kinase kinase kinase 1 isoform X2

  3. XM_047417220.1 → XP_047273176.1  mitogen-activated protein kinase kinase kinase 1 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    57643875..57724397
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352643.1 → XP_054208618.1  mitogen-activated protein kinase kinase kinase 1 isoform X1

  2. XM_054352642.1 → XP_054208617.1  mitogen-activated protein kinase kinase kinase 1 isoform X3

  3. XM_054352645.1 → XP_054208620.1  mitogen-activated protein kinase kinase kinase 1 isoform X2

  4. XM_054352644.1 → XP_054208619.1  mitogen-activated protein kinase kinase kinase 1 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13233.4 GenPept UniProtKB/Swiss-Prot:Q13233

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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