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MAPKAPK2 MAPK activated protein kinase 2 [ Homo sapiens (human) ]

Gene ID: 9261, updated on 2-Nov-2024

Summary

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Official Symbol
MAPKAPK2provided by HGNC
Official Full Name
MAPK activated protein kinase 2provided by HGNC
Primary source
HGNC:HGNC:6887
See related
Ensembl:ENSG00000162889 MIM:602006; AllianceGenome:HGNC:6887
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
MK2; MK-2; MAPKAP-K2
Summary
This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 54.9), heart (RPKM 45.1) and 25 other tissues See more
Orthologs
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Genomic context

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See MAPKAPK2 in Genome Data Viewer
Location:
1q32.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (206684905..206734281)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (205949085..205998488)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (206858250..206907626)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1759 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1760 Neighboring gene DYRK3 antisense RNA 1 Neighboring gene dual specificity tyrosine phosphorylation regulated kinase 3 Neighboring gene uncharacterized LOC124904496 Neighboring gene Sharpr-MPRA regulatory region 10950 Neighboring gene uncharacterized LOC124904495 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1761 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1762 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1763 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1764 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:206860855-206861416 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:206861417-206861978 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2412 Neighboring gene ribosomal protein S14 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 3087 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:206895773-206896486 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2414 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1765 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1766 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2415 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2416 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2417 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:206937123-206937321 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2418 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2419 Neighboring gene CRISPRi-FlowFISH-validated IL10 regulatory element GRCh37_chr1:206945468-206946089 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2420 Neighboring gene interleukin 10 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2421 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2422 Neighboring gene CRISPRi-FlowFISH-validated IL10 regulatory elements GRCh37_chr1:206966528-206967028 and GRCh37_chr1:206966531-206967031 Neighboring gene interleukin 19 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2423 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2424 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2425 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1767 Neighboring gene uncharacterized LOC105372878

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. The MAP kinase-activated protein kinase 2 (MK2) contributes to the Shiga toxin-induced inflammatory response. Saenz JB, et al. Cell Microbiol, 2010 Apr 1. PMID 19951368, Free PMC Article
  2. Decreased p38 MAPK activity in end-stage failing human myocardium: p38 MAPK alpha is the predominant isoform expressed in human heart. Lemke LE, et al. J Mol Cell Cardiol, 2001 Aug. PMID 11448140
  3. MK2-TNF-Signaling Comes Full Circle. Menon MB, et al. Trends Biochem Sci, 2018 Mar. PMID 29275999
  4. The MAPK-activated protein kinase 2 mediates gemcitabine sensitivity in pancreatic cancer cells. Köpper F, et al. Cell Cycle, 2014. PMID 24556918, Free PMC Article
  5. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Kumar B, et al. Cancer Res, 2010 Jan 15. PMID 20068172

See all (192) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer.
    Title: Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer.
  2. Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2.
    Title: Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2.
  3. MK2 degradation as a sensor of signal intensity that controls stress-induced cell fate.
    Title: MK2 degradation as a sensor of signal intensity that controls stress-induced cell fate.
  4. MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.
    Title: MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.
  5. Alternative Translation Initiation Generates a Functionally Distinct Isoform of the Stress-Activated Protein Kinase MK2 with distinct physiological properties.
    Title: Alternative Translation Initiation Generates a Functionally Distinct Isoform of the Stress-Activated Protein Kinase MK2.
  6. our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers.
    Title: Sophoridine Inhibits Human Colorectal Cancer Progression via Targeting MAPKAPK2.
  7. Studies present evidence that MK2 play a central role in the regulation of the inflammatory pathways in chronic airway inflammatory diseases. [review]
    Title: Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders.
  8. Overexpression of microRNA-490-3p alleviates inflammation and apoptosis via targeting MK2, thereafter promoting spinal cord injury recovery.
    Title: MicroRNA-490-3p inhibits inflammation and apoptosis induced by spinal cord injury via targeting MK2.
  9. The MK2 phosphorylates a cytoplasmic pool of RIPK1 that presumably subsequently integrates complex I, while IKKalpha/beta phosphorylate RIPK1 directly in complex I.
    Title: MK2 puts an additional brake on RIPK1 cytotoxic potential.
  10. Altogether, MAPKAPK2 is responsible for regulating the transcript stability and is functionally important to modulate Head and neck squamous-cell carcinoma pathogenesis.
    Title: MAPKAPK2 plays a crucial role in the progression of head and neck squamous cell carcinoma by regulating transcript stability.
Submit: New GeneRIF Correction See all GeneRIFs (77)

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
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
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

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 decreases adult neural progenitor cell proliferation via the p38 MAPK-MAPKAPK2-Cdc25C signaling pathway PubMed
Vpr vpr Kinase Srk1/MK2 is required for the Vpr-mediated nuclear export of Cdc25 PubMed

Go to the HIV-1, Human Interaction Database

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 calcium-dependent protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium/calmodulin-dependent protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calmodulin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables histone H2AS1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables mitogen-activated protein kinase binding IBA
Inferred from Biological aspect of Ancestor
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 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 3'-UTR-mediated mRNA stabilization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in DNA damage response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in MAPK cascade TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to vascular endothelial growth factor stimulus IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to vascular endothelial growth factor stimulus IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in inner ear development IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in leukotriene metabolic process TAS
Traceable Author Statement
more info
  
involved_in macropinocytosis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in p38MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of macrophage cytokine production IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of tumor necrosis factor production IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of cellular response to heat TAS
Traceable Author Statement
more info
  
involved_in regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of mRNA stability TAS
Traceable Author Statement
more info
  
involved_in regulation of tumor necrosis factor production IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of tumor necrosis factor-mediated signaling pathway TAS
Traceable Author Statement
more info
  
involved_in response to cytokine IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in response to cytokine IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to lipopolysaccharide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in toll-like receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in toll-like receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in vascular endothelial growth factor receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in vascular endothelial growth factor receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in vascular endothelial growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in centrosome IDA
Inferred from Direct Assay
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
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
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
MAP kinase-activated protein kinase 2
Names
MAPKAP kinase 2
mitogen-activated protein kinase-activated protein kinase 2
NP_004750.1
NP_116584.2
XP_005273410.1
XP_016858299.1
XP_047290374.1
XP_054195605.1
XP_054195606.1
XP_054195607.1

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_029640.1 RefSeqGene

    Range
    4886..54262
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004759.5 → NP_004750.1  MAP kinase-activated protein kinase 2 isoform 1

    See identical proteins and their annotated locations for NP_004750.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript but encodes the shorter isoform (1).
    Source sequence(s)
    AL591846, BC036060, BC052584, BU621009
    Consensus CDS
    CCDS1466.1
    UniProtKB/Swiss-Prot
    P49137
    Related
    ENSP00000294981.4, ENST00000294981.8
    Conserved Domains (2) summary
    smart00220
    Location:68 → 325
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14170
    Location:61 → 353
    STKc_MAPKAPK2; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2

  2. NM_032960.4 → NP_116584.2  MAP kinase-activated protein kinase 2 isoform 2

    See identical proteins and their annotated locations for NP_116584.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of the last exon compared to variant 1. The resulting isoform (2) has a longer and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AL591846, BC036060, BC052584, BU621009
    Consensus CDS
    CCDS31001.1
    UniProtKB/Swiss-Prot
    P49137, Q5SY30, Q5SY41, Q8IYD6
    Related
    ENSP00000356070.4, ENST00000367103.4
    Conserved Domains (1) summary
    cd14170
    Location:61 → 363
    STKc_MAPKAPK2; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    206684905..206734281
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005273353.4 → XP_005273410.1  MAP kinase-activated protein kinase 2 isoform X1

    Conserved Domains (2) summary
    smart00220
    Location:68 → 325
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14170
    Location:61 → 353
    STKc_MAPKAPK2; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2

  2. XM_017002810.2 → XP_016858299.1  MAP kinase-activated protein kinase 2 isoform X2

    Conserved Domains (1) summary
    cl21453
    Location:1 → 270
    PKc_like; Protein Kinases, catalytic domain

  3. XM_047434418.1 → XP_047290374.1  MAP kinase-activated protein kinase 2 isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    205949085..205998488
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054339630.1 → XP_054195605.1  MAP kinase-activated protein kinase 2 isoform X1

  2. XM_054339631.1 → XP_054195606.1  MAP kinase-activated protein kinase 2 isoform X2

  3. XM_054339632.1 → XP_054195607.1  MAP kinase-activated protein kinase 2 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P49137.1 GenPept UniProtKB/Swiss-Prot:P49137

Gene LinkOut

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