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MAPKAPK5 MAPK activated protein kinase 5 [ Homo sapiens (human) ]

Gene ID: 8550, updated on 5-Mar-2024

Summary

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Official Symbol
MAPKAPK5provided by HGNC
Official Full Name
MAPK activated protein kinase 5provided by HGNC
Primary source
HGNC:HGNC:6889
See related
Ensembl:ENSG00000089022 MIM:606723; AllianceGenome:HGNC:6889
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
MK5; MK-5; NCFD; PRAK; MAPKAP-K5
Summary
The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. The encoded protein is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. This kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2012]
Expression
Ubiquitous expression in small intestine (RPKM 3.1), colon (RPKM 2.9) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
12q24.12-q24.13
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (111842228..111902222)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (111819139..111879131)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (112280032..112340026)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:112123487-112124188 Neighboring gene acyl-CoA dehydrogenase family member 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:112194124-112194765 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:112195407-112196048 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:112196049-112196688 Neighboring gene NANOG hESC enhancer GRCh37_chr12:112199468-112200003 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:112204196-112204965 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:112210937-112211508 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7039 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:112228790-112229715 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:112229716-112230640 Neighboring gene aldehyde dehydrogenase 2 family member Neighboring gene microRNA 6761 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:112272338-112273217 Neighboring gene MAPKAPK5 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7040 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4876 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7041 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:112282209-112282377 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:112292092-112292249 Neighboring gene ribosomal protein S2 pseudogene 41 Neighboring gene ADAM metallopeptidase domain 1A (pseudogene) Neighboring gene transmembrane protein 116 Neighboring gene MPRA-validated peak1957 silencer Neighboring gene ADAM metallopeptidase domain 1B (pseudogene) Neighboring gene MPRA-validated peak1958 silencer Neighboring gene Sharpr-MPRA regulatory region 5697 Neighboring gene solute carrier family 25 member 3 pseudogene 2

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
  • 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. Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up. Vecchio D, et al. Clin Genet, 2022 Aug. PMID 35575217, Free PMC Article
  2. Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly. Horn D, et al. Genet Med, 2021 Apr. PMID 33442026
  3. MK5 is degraded in response to doxorubicin and negatively regulates doxorubicin-induced apoptosis in hepatocellular carcinoma cells. Zhou J, et al. Biochem Biophys Res Commun, 2012 Oct 26. PMID 23022185
  4. Regulation of PRAK subcellular location by p38 MAP kinases. New L, et al. Mol Biol Cell, 2003 Jun. PMID 12808055, Free PMC Article
  5. Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Perfetti V, et al. Blood, 2002 Aug 1. PMID 12130507

See all (67) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Consolidating the association of biallelic MAPKAPK5 pathogenic variants with a distinct syndromic neurodevelopmental disorder.
    Title: Consolidating the association of biallelic MAPKAPK5 pathogenic variants with a distinct syndromic neurodevelopmental disorder.
  2. The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-beta/beta-catenin signaling in HCC.
    Title: The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC.
  3. Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up.
    Title: Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19 months of follow-up.
  4. TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies.
    Title: TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies.
  5. MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis.
    Title: MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis.
  6. Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly.
    Title: Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly.
  7. Study identified the serine/threonine kinase MK5 as a positive regulator of YAP. MK5 physically interacted with YAP and counteracted CK1delta/epsilon-mediated YAP ubiquitination and degradation independent of LATS1/2. MK5 upregulation was associated with high levels of YAP expression and poor prognosis in clinical tumor samples, confirming its important role for YAP activity in human cancer.
    Title: MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers.
  8. MK5 is being discussed as a putative novel regulator of cardiac fibroblast function. (Review)
    Title: MK5: A novel regulator of cardiac fibroblast function?
  9. PRAK might be a potential therapeutic target of Alzheimer's disease involved in receptor for advanced glycation end products-mediated cell signaling induced by Abeta
    Title: The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer's disease pathogenesis.
  10. Plasma MAPKAPK5 protein was found to positively associate with the 10-year change in paired associates learning assessment in asymptomatic older twins.
    Title: Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Neurocardiofaciodigital syndrome
MedGen: C5677020 OMIM: 619869 GeneReviews: Not available
not available

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 TAS
Traceable Author Statement
more info
 PubMed 
enables calcium-dependent protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calmodulin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calmodulin-dependent protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables mitogen-activated protein kinase binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables p53 binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity EXP
Inferred from Experiment
more info
 PubMed 
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in Ras protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in Ras protein signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular senescence TAS
Traceable Author Statement
more info
  
involved_in negative regulation of TOR signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of TOR signaling ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in peptidyl-serine phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of dendritic spine development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of telomerase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of telomere capping IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of telomere maintenance via telomerase IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein autophosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of signal transduction by p53 class mediator TAS
Traceable Author Statement
more info
  
involved_in regulation of translation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in stress-induced premature senescence IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of protein-containing complex IEA
Inferred from Electronic Annotation
more info
  
located_in septin cytoskeleton IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
MAP kinase-activated protein kinase 5
Names
MAPKAP kinase 5
MAPKAPK-5
mitogen-activated protein kinase-activated protein kinase 5
p38-regulated/activated protein kinase
NP_001358408.1
NP_001358409.1
NP_001358410.1
NP_001358411.1
NP_001358412.1
NP_001358413.1
NP_001358414.1
NP_001358415.1
NP_001358416.1
NP_003659.2
NP_620777.1

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.

mRNA and Protein(s)

  1. NM_001371479.1 → NP_001358408.1  MAP kinase-activated protein kinase 5 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cd14171
    Location:15 → 304
    STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5

  2. NM_001371480.1 → NP_001358409.1  MAP kinase-activated protein kinase 5 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cd14171
    Location:15 → 304
    STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5

  3. NM_001371481.1 → NP_001358410.1  MAP kinase-activated protein kinase 5 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cl21453
    Location:15 → 277
    PKc_like; Protein Kinases, catalytic domain

  4. NM_001371482.1 → NP_001358411.1  MAP kinase-activated protein kinase 5 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cl21453
    Location:15 → 274
    PKc_like; Protein Kinases, catalytic domain

  5. NM_001371483.1 → NP_001358412.1  MAP kinase-activated protein kinase 5 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cl21453
    Location:15 → 274
    PKc_like; Protein Kinases, catalytic domain

  6. NM_001371484.1 → NP_001358413.1  MAP kinase-activated protein kinase 5 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cl21453
    Location:15 → 270
    PKc_like; Protein Kinases, catalytic domain

  7. NM_001371485.1 → NP_001358414.1  MAP kinase-activated protein kinase 5 isoform 9

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cl21453
    Location:15 → 235
    PKc_like; Protein Kinases, catalytic domain

  8. NM_001371486.1 → NP_001358415.1  MAP kinase-activated protein kinase 5 isoform 10

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Conserved Domains (1) summary
    cl21453
    Location:15 → 235
    PKc_like; Protein Kinases, catalytic domain

  9. NM_001371487.1 → NP_001358416.1  MAP kinase-activated protein kinase 5 isoform 11

    Status: REVIEWED

    Source sequence(s)
    AC003029
    UniProtKB/TrEMBL
    R4GN33
    Related
    ENSP00000473467.1, ENST00000549875.1
    Conserved Domains (1) summary
    cl21453
    Location:15 → 205
    PKc_like; Protein Kinases, catalytic domain

  10. NM_003668.4 → NP_003659.2  MAP kinase-activated protein kinase 5 isoform 1

    See identical proteins and their annotated locations for NP_003659.2

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Consensus CDS
    CCDS44976.1
    UniProtKB/Swiss-Prot
    Q8IW41
    Related
    ENSP00000449667.2, ENST00000550735.7
    Conserved Domains (1) summary
    cd14171
    Location:15 → 304
    STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5

  11. NM_139078.3 → NP_620777.1  MAP kinase-activated protein kinase 5 isoform 2

    See identical proteins and their annotated locations for NP_620777.1

    Status: REVIEWED

    Source sequence(s)
    AC003029
    Consensus CDS
    CCDS44975.1
    UniProtKB/Swiss-Prot
    B3KVA5, O60491, Q86X46, Q8IW41, Q9BVX9, Q9UG86
    Related
    ENSP00000449381.2, ENST00000551404.7
    Conserved Domains (1) summary
    cd14171
    Location:15 → 304
    STKc_MAPKAPK5; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5

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_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    111842228..111902222
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    111819139..111879131
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IW41.2 GenPept UniProtKB/Swiss-Prot:Q8IW41

Gene LinkOut

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