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

Gene ID: 5607, updated on 2-Nov-2024

Summary

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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
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Genomic context

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See MAP2K5 in Genome Data Viewer
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_000015.10Genomic Context describing neighboring genes Neighboring gene IQCH antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9630 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9631 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:67833981-67834481 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6579 Neighboring gene chromosome 15 open reading frame 61 Neighboring gene NANOG hESC enhancer GRCh37_chr15:67840145-67840646 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6580 Neighboring gene MAP2K5 divergent transcript Neighboring gene uncharacterized LOC124903512 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 5 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_40692 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:67983795-67984354 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:68043019-68043520 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6581 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9633 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9634 Neighboring gene heart enhancer 7 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr15:68074255-68075090 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:68083192-68084061 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr15:68096122-68096984 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:68096985-68097845 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:68112196-68112794 Neighboring gene uncharacterized LOC124903570 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:68119115-68119753 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:68119754-68120391 Neighboring gene uncharacterized LOC105370870 Neighboring gene SKI family transcriptional corepressor 1

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 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. Mitogen/extracellular signal-regulated kinase kinase-5 promoter region polymorphisms affect the risk of sporadic colorectal cancer in a southern Chinese population. Diao D, et al. DNA Cell Biol, 2012 Mar. PMID 21861603, Free PMC Article
  2. The MAP2K5-linked SNP rs2241423 is associated with BMI and obesity in two cohorts of Swedish and Greek children. Rask-Andersen M, et al. BMC Med Genet, 2012 May 17. PMID 22594783, Free PMC Article
  3. Extracellular signal regulated kinase 5 (ERK5) is required for the differentiation of muscle cells. Dinev D, et al. EMBO Rep, 2001 Sep. PMID 11520859, Free PMC Article
  4. Whole exome and target sequencing identifies MAP2K5 as novel susceptibility gene for familial non-medullary thyroid carcinoma. Ye F, et al. Int J Cancer, 2019 Mar 15. PMID 30132833
  5. Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation. Li F, et al. J Cancer Res Clin Oncol, 2022 Dec. PMID 35713705

See all (105) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. MEK5 promotes lung adenocarcinoma.
    Title: MEK5 promotes lung adenocarcinoma.
  8. 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.
  9. MEK5 is a novel autophagy modulator
    Title: Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway.
  10. 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
Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.
EBI GWAS Catalog
Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.
EBI GWAS Catalog
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
EBI GWAS Catalog
Meta-analysis identifies common variants associated with body mass index in east Asians.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
EBI GWAS Catalog
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
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 activity IBA
Inferred from Biological aspect of Ancestor
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
  
enables protein tyrosine 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 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 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 protein phosphorylation IEA
Inferred from Electronic Annotation
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
NP_002748.1
NP_660143.1
XP_011520089.1
XP_011520090.1
XP_016877903.1
XP_047288812.1
XP_054234420.1
XP_054234421.1
XP_054234422.1
XP_054234423.1

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_029143.2 RefSeqGene

    Range
    5002..269413
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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 ...

  2. 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

  3. 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

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    67542703..67807114
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. XM_017022414.3 → XP_016877903.1  dual specificity mitogen-activated protein kinase kinase 5 isoform X3

  4. XM_047432856.1 → XP_047288812.1  dual specificity mitogen-activated protein kinase kinase 5 isoform X4

RNA

  1. XR_007064474.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    65364709..65628974
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054378446.1 → XP_054234421.1  dual specificity mitogen-activated protein kinase kinase 5 isoform X2

  2. XM_054378445.1 → XP_054234420.1  dual specificity mitogen-activated protein kinase kinase 5 isoform X1

  3. XM_054378447.1 → XP_054234422.1  dual specificity mitogen-activated protein kinase kinase 5 isoform X3

  4. XM_054378448.1 → XP_054234423.1  dual specificity mitogen-activated protein kinase kinase 5 isoform X4

RNA

  1. XR_008488992.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. 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.

  2. 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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13163.2 GenPept UniProtKB/Swiss-Prot:Q13163

Gene LinkOut

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