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MAP2K1 mitogen-activated protein kinase kinase 1 [ Homo sapiens (human) ]

Gene ID: 5604, updated on 7-Apr-2024

Summary

Official Symbol
MAP2K1provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase 1provided by HGNC
Primary source
HGNC:HGNC:6840
See related
Ensembl:ENSG00000169032 MIM:176872; AllianceGenome:HGNC:6840
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
MEL; CFC3; MEK1; MKK1; MAPKK1; PRKMK1
Summary
The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in brain (RPKM 34.3), fat (RPKM 20.3) and 25 other tissues See more
Orthologs
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Genomic context

Location:
15q22.31
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (66386912..66491544)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (64208363..64313019)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (66679250..66783882)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene TIMELESS interacting protein Neighboring gene small Cajal body-specific RNA 14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9611 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9612 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6563 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6564 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:66681899-66682075 Neighboring gene ribosomal protein L9 pseudogene 25 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6565 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:66696135-66696928 Neighboring gene ATP synthase membrane subunit f pseudogene 6 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66720755-66721254 Neighboring gene ribosomal protein L35a pseudogene 32 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66763159-66763836 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9613 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9614 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66767223-66767899 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66768557-66769080 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66769081-66769604 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66788751-66789486 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66789487-66790222 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:66792902-66794101 Neighboring gene small nuclear RNA activating complex polypeptide 5 Neighboring gene microRNA 4512 Neighboring gene small nucleolar RNA, C/D box 18C Neighboring gene ribosomal protein L4

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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Cardiofaciocutaneous syndrome 3
MedGen: C3809006 OMIM: 615279 GeneReviews: Cardiofaciocutaneous Syndrome
Compare labs
Melorheostosis
MedGen: C3149631 OMIM: 155950 GeneReviews: Not available
Compare labs
Noonan syndrome
MedGen: C0028326 GeneReviews: Noonan Syndrome
Compare labs
Noonan syndrome 1
MedGen: C4551602 OMIM: 163950 GeneReviews: Noonan Syndrome
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2015-10-13)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2015-10-13)

ClinGen Genome Curation Page

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env The transcription factors and kinases c-Jun, JNK, MEK, p38 MAPK, STAT-3, JAK-1, TFII D, TFII F, eIF-4E, and RNA polymerase II are induced by HIV-1 gp120 PubMed
Nef nef HIV-1 Nef induces phosphorylation of MEK1 at position serine 298, which depends on Pak and Rac activity. The SH3 region mutation 72PXXP/AXXA75 in Nef results in loss of Pak association which decreases Nef-induced MEK1 phosphorylation PubMed
nef HIV-1 Nef causes the FMS N-glycosylation defect and induces relocalization of the GM130 by activating the p56Hck/MEK/ERK/GRASP65 phosphorylation cascade in the Golgi PubMed
nef HIV-1 Nef expression in primary T cells upregulates MEK1/2 activities, which induces the increased phosphorylation of ERK1/2 PubMed
Tat tat HIV-1 Tat activates PRKCQ (PKC-theta) kinase activity, which leads to RELA (NFkB), NRAS, RAF1, MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK3 (ERK1), and MAPK1 (ERK2) activation, in Jurkat T cells that stably express Tat PubMed
tat HIV-1 Tat increases phosphorylation of ERK1/2, JNK1/2, p38, AKT1, MEK-1, and STAT-1alpha in Muller glia PubMed
tat HIV-1 Tat upregulates the expression of platelet-derived growth factor subunit B homodimer through activation of the PDGFR-B/MEK/NF-kappaB pathway in human brain microvascular pericytes PubMed
tat HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways PubMed
tat Tat and IFN-gamma synergistically induce the expression of CXCL10, which is inhibited by MEK1/2 inhibitor and the p38 mitogen-activated protein kinase (MAPK) inhibitor PubMed
tat HIV-1 Tat in combination with KSHV kaposin A activates the MEK/ERK, STAT3, and PI3K/Akt signals in NIH3T3 cells PubMed
tat HIV-1 Tat-peptide(48-60) inhibits AGC-family kinases (PKB, SGK1, S6K1, MSK1), CAMK-family kinases (CAMK1 and MELK) and a STE family kinase (MKK1) PubMed
tat HIV-1 Tat activates mitogen-activated protein kinases ERK1 and ERK2 through the activation of MEK1 and MEK2, leading to induction of IL-8, IL-10, IP-10, iNOS, superoxide and TNF-alpha, as well as the activation of CREB and increased albumin permeability PubMed
Vpr vpr Inhibition of MEK1,2 impairs HIV-1 Vpr-induced BID cleavage PubMed
reverse transcriptase gag-pol MEK1 in HIV-1 producer cells is able to activate virion-associated MAPK in trans, and the activated MAPK facilitates efficient disengagement of the HIV-1 reverse transcription complex from the cell membrane and subsequent nuclear translocation PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
 
enables MAP kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables MAP kinase kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables MAP-kinase scaffold activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables protein binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein kinase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
enables protein kinase activity TAS
Traceable Author Statement
more info
PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
 
enables protein serine/threonine kinase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
enables protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 
enables protein serine/threonine/tyrosine kinase activity TAS
Traceable Author Statement
more info
PubMed 
enables protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
enables scaffold protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in Bergmann glial cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in ERBB2-ERBB3 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in ERK1 and ERK2 cascade TAS
Traceable Author Statement
more info
 
involved_in MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in Schwann cell development IEA
Inferred from Electronic Annotation
more info
 
involved_in cell motility IEA
Inferred from Electronic Annotation
more info
 
involved_in cellular senescence IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cerebellar cortex formation IEA
Inferred from Electronic Annotation
more info
 
involved_in chemotaxis TAS
Traceable Author Statement
more info
PubMed 
involved_in endodermal cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in epithelial cell proliferation involved in lung morphogenesis IEA
Inferred from Electronic Annotation
more info
 
involved_in face development IEA
Inferred from Electronic Annotation
more info
 
involved_in heart development IEA
Inferred from Electronic Annotation
more info
 
involved_in insulin-like growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in keratinocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in labyrinthine layer development IEA
Inferred from Electronic Annotation
more info
 
involved_in myelination IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in placenta blood vessel development IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of axonogenesis IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of endodermal cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of Golgi inheritance TAS
Traceable Author Statement
more info
PubMed 
involved_in regulation of axon regeneration IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of early endosome to late endosome transport TAS
Traceable Author Statement
more info
PubMed 
involved_in regulation of stress-activated MAPK cascade TAS
Traceable Author Statement
more info
PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
PubMed 
involved_in thymus development IEA
Inferred from Electronic Annotation
more info
 
involved_in thyroid gland development IEA
Inferred from Electronic Annotation
more info
 
involved_in trachea formation IEA
Inferred from Electronic Annotation
more info
 
involved_in type B pancreatic cell proliferation IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
located_in Golgi apparatus TAS
Traceable Author Statement
more info
PubMed 
located_in centrosome IEA
Inferred from Electronic Annotation
more info
 
located_in cytosol IDA
Inferred from Direct Assay
more info
 
located_in cytosol TAS
Traceable Author Statement
more info
PubMed 
located_in early endosome TAS
Traceable Author Statement
more info
PubMed 
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
located_in focal adhesion TAS
Traceable Author Statement
more info
PubMed 
located_in late endosome TAS
Traceable Author Statement
more info
PubMed 
located_in mitochondrion TAS
Traceable Author Statement
more info
PubMed 
located_in nucleus TAS
Traceable Author Statement
more info
PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 

General protein information

Preferred Names
dual specificity mitogen-activated protein kinase kinase 1
Names
ERK activator kinase 1
MAPK/ERK kinase 1
MAPKK 1
MEK 1
protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1)
NP_001397994.1
NP_002746.1
XP_011520085.1
XP_016877900.1
XP_054234418.1
XP_054234419.1

NCBI Reference Sequences (RefSeq)

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_008305.1 RefSeqGene

    Range
    5001..109672
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_725

mRNA and Protein(s)

  1. NM_001411065.1NP_001397994.1  dual specificity mitogen-activated protein kinase kinase 1 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC011276, AC116913
    Consensus CDS
    CCDS92029.1
    UniProtKB/TrEMBL
    A0A8I5KYS7
    Related
    ENSP00000510309.1, ENST00000693150.1
  2. NM_002755.4NP_002746.1  dual specificity mitogen-activated protein kinase kinase 1 isoform 1

    See identical proteins and their annotated locations for NP_002746.1

    Status: REVIEWED

    Source sequence(s)
    AK291500, AK312356, BG709050, CA419665, L11284
    Consensus CDS
    CCDS10216.1
    UniProtKB/Swiss-Prot
    Q02750
    UniProtKB/TrEMBL
    A0A8I5KRX5, A4QPA9
    Related
    ENSP00000302486.5, ENST00000307102.10
    Conserved Domains (1) summary
    cd06650
    Location:62380
    PKc_MEK1; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) 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_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    66386912..66491544
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017022411.3XP_016877900.1  dual specificity mitogen-activated protein kinase kinase 1 isoform X2

    UniProtKB/TrEMBL
    A0A8I5KRX5
    Conserved Domains (2) summary
    smart00220
    Location:68335
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl21453
    Location:62354
    PKc_like; Protein Kinases, catalytic domain
  2. XM_011521783.4XP_011520085.1  dual specificity mitogen-activated protein kinase kinase 1 isoform X1

    See identical proteins and their annotated locations for XP_011520085.1

    UniProtKB/TrEMBL
    A0A8I5KRX5, B4DFY5
    Related
    ENSP00000508437.1, ENST00000692683.1
    Conserved Domains (1) summary
    cd06650
    Location:40358
    PKc_MEK1; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    64208363..64313019
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054378444.1XP_054234419.1  dual specificity mitogen-activated protein kinase kinase 1 isoform X2

  2. XM_054378443.1XP_054234418.1  dual specificity mitogen-activated protein kinase kinase 1 isoform X1

    UniProtKB/TrEMBL
    B4DFY5