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

    Gene ID: 5607, updated on 10-Dec-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
    mouse all
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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: 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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    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)

    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 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
    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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    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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