MAP2K5 mitogen-activated protein kinase kinase 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAP2K5provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase 5provided by HGNC
Primary source: HGNC:HGNC:6845
See related: Ensembl:ENSG00000137764 MIM:602520; AllianceGenome:HGNC:6845
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: MEK5; MAPKK5; PRKMK5; HsT17454
Summary: The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]
Expression: Ubiquitous expression in ovary (RPKM 2.0), testis (RPKM 1.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q23

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (67542703..67807114)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (65364709..65628974)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (67835041..68099452)

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: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.
Title: Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.
MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells.
Title: MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells.
Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation.
Title: Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation.
Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to the third generation EGFR inhibitor, osimertinib, via enhancing Bim-dependent apoptosis.
Title: Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to the third generation EGFR inhibitor, osimertinib, via enhancing Bim-dependent apoptosis.
The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells.
Title: The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells.
Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults.
Title: Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults.
MEK5 promotes lung adenocarcinoma.
Title: MEK5 promotes lung adenocarcinoma.
The MEK5-ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer.
Title: The MEK5-ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer.
MEK5 is a novel autophagy modulator
Title: Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway.
MAP2K5/SKOR1 may be associated with Chinese essential tremor patients.
Title: A haplotype of MAP2K5/SKOR1 was associated with essential tremor in Chinese population.

Submit: New GeneRIF Correction See all GeneRIFs (42)

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
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies common variants associated with body mass index in east Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. EBI GWAS Catalog EBI GWAS CatalogPubMed
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_7855-7856:996688103:1 (e-PCR)
- UniSTS:269838

AFM276YB5 (e-PCR)
- UniSTS:45841

WI-19238 (e-PCR)
- UniSTS:2868

SHGC-34905 (e-PCR)
- UniSTS:32316

D15S1220 (e-PCR)
- UniSTS:23362

BCD1447 (e-PCR)
- UniSTS:19524

RH102019 (e-PCR)
- UniSTS:96353

SHGC-147756 (e-PCR)
- UniSTS:175990

STS-H66629 (e-PCR)
- UniSTS:43383

D15S1242 (e-PCR)
- UniSTS:73345

SHGC-156118 (e-PCR)
- UniSTS:182921

SHGC-172623 (e-PCR)
- UniSTS:182928

G63218 (e-PCR)
- UniSTS:140191

D15S1015 (e-PCR)
- UniSTS:64434

RH67871 (e-PCR)
- UniSTS:65233

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 histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
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	TAS Traceable Author Statement more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in ERK5 cascade	IEA Inferred from Electronic Annotation 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 MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular response to growth factor stimulus	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular response to laminar fluid shear stress	TAS Traceable Author Statement more info	PubMed
involved_in chromatin remodeling	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 negative regulation of canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of cell migration involved in sprouting angiogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of chemokine (C-X-C motif) ligand 2 production	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of heterotypic cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of interleukin-8 production	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of response to cytokine stimulus	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of smooth muscle cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in spindle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 5

Names: MAP kinase kinase 5; MAP kinase kinase MEK5b; MAPK/ERK kinase 5; MAPKK 5; MEK 5

NP_001193733.1

EC 2.7.12.2

NP_002748.1

EC 2.7.12.2

NP_660143.1

EC 2.7.12.2

XP_011520089.1

EC 2.7.12.2

XP_011520090.1

EC 2.7.12.2

XP_016877903.1

EC 2.7.12.2

XP_047288812.1

EC 2.7.12.2

XP_054234420.1

EC 2.7.12.2

XP_054234421.1

EC 2.7.12.2

XP_054234422.1

EC 2.7.12.2

XP_054234423.1

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_029143.2 RefSeqGene

Range

5002..269413

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001206804.2 → NP_001193733.1 dual specificity mitogen-activated protein kinase kinase 5 isoform C

See identical proteins and their annotated locations for NP_001193733.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (C) has a shorter and distinct N-terminus compared to isoform A.

Source sequence(s)

AK293459, BC008838

Consensus CDS

CCDS55970.1

UniProtKB/TrEMBL

B2RD76

Related

ENSP00000346493.5, ENST00000354498.9

Conserved Domains (2) summary

cd06619
Location:128 → 406

PKc_MKK5; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5

cl02720
Location:10 → 71

PB1; The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 ...
NM_002757.4 → NP_002748.1 dual specificity mitogen-activated protein kinase kinase 5 isoform B

See identical proteins and their annotated locations for NP_002748.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (B) has the same N- and C-termini but is shorter compared to isoform A.

Source sequence(s)

AC009292, AC016355, AC103753

Consensus CDS

CCDS42051.1

UniProtKB/TrEMBL

B2RD76

Related

ENSP00000378859.2, ENST00000395476.6

Conserved Domains (2) summary

cd06395
Location:17 → 107

PB1_Map2k5; PB1 domain is essential part of the mitogen-activated protein kinase kinase 5 (Map2k5, alias MEK5) one of the key member of the signaling kinases cascade which involved in angiogenesis and early cardiovascular development. The PB1 domain of Map2k5 ...

cd06619
Location:164 → 432

PKc_MKK5; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5
NM_145160.3 → NP_660143.1 dual specificity mitogen-activated protein kinase kinase 5 isoform A

See identical proteins and their annotated locations for NP_660143.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (A).

Source sequence(s)

AC009292, AC016355, AC103753

Consensus CDS

CCDS10224.1

UniProtKB/Swiss-Prot

B4DE43, Q13163, Q92961, Q92962

UniProtKB/TrEMBL

B2RD76

Related

ENSP00000178640.5, ENST00000178640.10

Conserved Domains (2) summary

cd06395
Location:17 → 107

PB1_Map2k5; PB1 domain is essential part of the mitogen-activated protein kinase kinase 5 (Map2k5, alias MEK5) one of the key member of the signaling kinases cascade which involved in angiogenesis and early cardiovascular development. The PB1 domain of Map2k5 ...

cd06619
Location:164 → 442

PKc_MKK5; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5

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

67542703..67807114

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011521788.4 → XP_011520090.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X2

Conserved Domains (2) summary

cd06395
Location:17 → 107

PB1_Map2k5; PB1 domain is essential part of the mitogen-activated protein kinase kinase 5 (Map2k5, alias MEK5) one of the key member of the signaling kinases cascade which involved in angiogenesis and early cardiovascular development. The PB1 domain of Map2k5 ...

cl21453
Location:164 → 282

PKc_like; Protein Kinases, catalytic domain
XM_011521787.4 → XP_011520089.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X1

Conserved Domains (2) summary

cd06395
Location:17 → 107

PB1_Map2k5; PB1 domain is essential part of the mitogen-activated protein kinase kinase 5 (Map2k5, alias MEK5) one of the key member of the signaling kinases cascade which involved in angiogenesis and early cardiovascular development. The PB1 domain of Map2k5 ...

cl21453
Location:164 → 282

PKc_like; Protein Kinases, catalytic domain
XM_017022414.3 → XP_016877903.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X3
XM_047432856.1 → XP_047288812.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X4

RNA

XR_007064474.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

65364709..65628974

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054378446.1 → XP_054234421.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X2
XM_054378445.1 → XP_054234420.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X1
XM_054378447.1 → XP_054234422.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X3
XM_054378448.1 → XP_054234423.1 dual specificity mitogen-activated protein kinase kinase 5 isoform X4

RNA

XR_008488992.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_145161.1: Suppressed sequence

Description

NM_145161.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_145162.1: Suppressed sequence

Description

NM_145162.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.