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

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: mouse all
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Genomic context

Location:: 15q22.31

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (66386912..66491544)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (64208363..64313019)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (66679250..66783882)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MAP2K1-mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with BRAF V600E mutations.
Title: MAP2K1-mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with BRAF V600E mutations.
Activating mutations drive human MEK1 kinase using a gear-shifting mechanism.
Title: Activating mutations drive human MEK1 kinase using a gear-shifting mechanism.
Modeling Osteoarthritis: MiR-16-5p Attenuates IL-1beta Induced Chondrocyte Dysfunction by Targeting MAP2K1 through the MAPK Pathway.
Title: Modeling Osteoarthritis: MiR-16-5p Attenuates IL-1β Induced Chondrocyte Dysfunction by Targeting MAP2K1 through the MAPK Pathway.
Evolutionary history of MEK1 illuminates the nature of deleterious mutations.
Title: Evolutionary history of MEK1 illuminates the nature of deleterious mutations.
Clinical associations of BRAF and MAP2K1 mutations in pediatric Langerhans cell histiocytosis: When 1 + 1 = 3.
Title: Clinical associations of BRAF and MAP2K1 mutations in pediatric Langerhans cell histiocytosis: When 1 + 1 = 3.
Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients.
Title: Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients.
Response to MEK Inhibitor Therapy in MAP2K1 (MEK1) K57N Non-Small-Cell Lung Cancer and Genomic Landscape of MAP2K1 Mutations in Non-Small-Cell Lung Cancer.
Title: Response to MEK Inhibitor Therapy in MAP2K1 (MEK1) K57N Non-Small-Cell Lung Cancer and Genomic Landscape of MAP2K1 Mutations in Non-Small-Cell Lung Cancer.
High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer.
Title: High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer.
Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children.
Title: Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children.
Structure of mitogen-activated protein kinase kinase 1 in the DFG-out conformation.
Title: Structure of mitogen-activated protein kinase kinase 1 in the DFG-out conformation.

Submit: New GeneRIF Correction See all GeneRIFs (283)

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
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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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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

NoName (e-PCR)
- UniSTS:489729

MAP2K1_2178 (e-PCR)
- UniSTS:280835

RH28581 (e-PCR)
- UniSTS:88953

RH68988 (e-PCR)
- UniSTS:89532

D15S534 (e-PCR)
- UniSTS:149235

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase activity	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 histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
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 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 JNK cascade	IEA Inferred from Electronic Annotation 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 chromatin remodeling	IEA Inferred from Electronic Annotation more info
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 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

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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

EC 2.7.12.2

NP_002746.1

EC 2.7.12.2

XP_011520085.1

EC 2.7.12.2

XP_016877900.1

EC 2.7.12.2

XP_054234418.1

EC 2.7.12.2

XP_054234419.1

EC 2.7.12.2

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

NG_008305.1 RefSeqGene

Range

5001..109672

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_725

mRNA and Protein(s)

NM_001411065.1 → NP_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

A0A8I5KRX5, A0A8I5KYS7

Related

ENSP00000510309.1, ENST00000693150.1
NM_002755.4 → NP_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:62 → 380

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

66386912..66491544

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A8I5KRX5

Conserved Domains (2) summary

smart00220
Location:68 → 335

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:62 → 354

PKc_like; Protein Kinases, catalytic domain
XM_011521783.4 → XP_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:40 → 358

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

NC_060939.1 Alternate T2T-CHM13v2.0

Range

64208363..64313019

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A8I5KRX5
XM_054378443.1 → XP_054234418.1 dual specificity mitogen-activated protein kinase kinase 1 isoform X1

UniProtKB/TrEMBL

A0A8I5KRX5, B4DFY5