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

    Gene ID: 4214, updated on 27-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (56815549..56896152)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (57643875..57724397)
    RS_2024_09 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. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1. Glubb DM, et al. Am J Hum Genet, 2015 Jan 8. PMID 25529635, Free PMC Article
    2. Multilocus analysis of candidate genes involved in neurogenic inflammation in pediatric asthma and related phenotypes: a case-control study. Szczepankiewicz A, et al. J Asthma, 2012 May. PMID 22468730
    3. A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers. Filipčík P, et al. Proc Natl Acad Sci U S A, 2020 Sep 1. PMID 32817551, Free PMC Article
    4. A novel missense heterozygous mutation in MAP3K1 gene causes 46, XY disorder of sex development: case report and literature review. Al Shamsi A, et al. Mol Genet Genomic Med, 2020 Nov. PMID 32986312, Free PMC Article
    5. Nonsense-associated altered splicing of MAP3K1 in two siblings with 46,XY disorders of sex development. Igarashi M, et al. Sci Rep, 2020 Oct 15. PMID 33060765, Free PMC Article

    See all (201) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.
      Title: A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.
    2. Mitogen-activated protein kinase kinase kinase 1 facilitates the temozolomide resistance and migration of GBM via the MEK/ERK signalling.
      Title: Mitogen-activated protein kinase kinase kinase 1 facilitates the temozolomide resistance and migration of GBM via the MEK/ERK signalling.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review.
      Title: Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (97)

    Phenotypes

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    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
    		Compare labs

    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)

    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 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
    		  
    located_in tight junction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    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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    NEW Try the new Transcript table

    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_2024_08

    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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