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MAPKAPK3 MAPK activated protein kinase 3 [ Homo sapiens (human) ]

Gene ID: 7867, updated on 3-Apr-2024

Summary

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Official Symbol
MAPKAPK3provided by HGNC
Official Full Name
MAPK activated protein kinase 3provided by HGNC
Primary source
HGNC:HGNC:6888
See related
Ensembl:ENSG00000114738 MIM:602130; AllianceGenome:HGNC:6888
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
3PK; MK3; MK-3; MDPT3; MAPKAP3; MAPKAP-K3; MAPKAPK-3
Summary
This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
Expression
Broad expression in heart (RPKM 55.1), bone marrow (RPKM 29.6) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
3p21.2
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (50611520..50649291)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (50641158..50679247)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (50649308..50686722)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377083 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:50575146-50575387 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50576885-50577561 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50584920-50585829 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50586902-50587840 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14398 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19907 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50619223-50619724 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50619725-50620224 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50621581-50622099 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19909 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19911 Neighboring gene VISTA enhancer hs1747 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14399 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50648164-50648724 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14400 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19912 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19913 Neighboring gene chromosome 3 open reading frame 18 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50654302-50655255 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50655256-50656208 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14405 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50662917-50663693 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50684509-50685008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50686500-50687053 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50689443-50690376 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50688509-50689442 Neighboring gene HemK methyltransferase family member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14406 Neighboring gene cytokine inducible SH2 containing protein Neighboring gene long intergenic non-protein coding RNA 2019 Neighboring gene microRNA 4787 Neighboring gene dedicator of cytokinesis 3

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. Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights. Jean-Charles A, et al. Ophthalmology, 2016 Oct. PMID 27474146
  2. High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand. Cheng R, et al. Protein Sci, 2010 Jan. PMID 19937655, Free PMC Article
  3. A polymorphism in MAPKAPK3 affects response to interferon therapy for chronic hepatitis C. Tsukada H, et al. Gastroenterology, 2009 May. PMID 19208361
  4. Mitogen-activated 3p kinase is active in the nucleus. Zakowski V, et al. Exp Cell Res, 2004 Sep 10. PMID 15302577
  5. Gene activity changes in ischemically preconditioned rabbit heart gene: discovery array study. Simkhovich BZ, et al. Heart Dis, 2002 Mar-Apr. PMID 11975836

See all (61) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The natural history of MCRPE is in relation to the role of MAPKAPK3 in BM modeling, vascular endothelial growth factor activity, retinal pigment epithelial responses
    Title: Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights.
  2. A dominant mutation in MAPKAPK3 causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium.
    Title: A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium.
  3. MK3 modulation affects BMI1-dependent and independent cell cycle check-points
    Title: MK3 modulation affects BMI1-dependent and independent cell cycle check-points.
  4. findings reveal MK2/MK3 as crucial stress-responsive kinases that promote autophagy through Beclin 1 S90 phosphorylation
    Title: The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation.
  5. Hepatitis C virus core protein interacted with MAPKAPK3 through amino acid residues 41 to 75 of core and the N-terminal half of kinase domain of MAPKAPK3.
    Title: Modulation of mitogen-activated protein kinase-activated protein kinase 3 by hepatitis C virus core protein.
  6. Identified CREB activators MAPKAPK3 and FHL5 as mediators of intimal hyperplasia in vein graft samples.
    Title: Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia.
  7. Observational study of gene-disease association. (HuGE Navigator)
    Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
  8. A high-resolution (1.9 A) crystal structure of the highly homologous MK3 in complex with a pharmaceutical lead compound is presented.
    Title: High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand.
  9. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
    Title: Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population.
  10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
    Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Submit: New GeneRIF Correction See all GeneRIFs (12)

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
Patterned macular dystrophy 3
MedGen: C4310713 OMIM: 617111 GeneReviews: Not available
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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 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 
Process Evidence Code Pubs
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in macropinocytosis 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 peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autophosphorylation IBA
Inferred from Biological aspect of Ancestor
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 signal transduction TAS
Traceable Author Statement
more info
 PubMed 
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 TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
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
  

General protein information

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Preferred Names
MAP kinase-activated protein kinase 3
Names
MAPKAP kinase 3
chromosome 3p kinase
mitogen-activated protein kinase-activated protein kinase 3
NP_001230854.1
NP_001230855.1
NP_004626.1
XP_047304839.1
XP_047304840.1
XP_047304841.1
XP_047304842.1
XP_047304843.1
XP_054203772.1
XP_054203773.1
XP_054203774.1

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_051548.1 RefSeqGene

    Range
    10290..42430
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243925.2 → NP_001230854.1  MAP kinase-activated protein kinase 3

    See identical proteins and their annotated locations for NP_001230854.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
    Source sequence(s)
    AC096920, BE301676, BM848086, U09578
    Consensus CDS
    CCDS2832.1
    UniProtKB/Swiss-Prot
    B5BU67, Q16644
    UniProtKB/TrEMBL
    A8K4K4, B2R8Z2, B5BUJ8
    Related
    ENSP00000478922.1, ENST00000621469.5
    Conserved Domains (1) summary
    cd14172
    Location:39 → 304
    STKc_MAPKAPK3; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3

  2. NM_001243926.2 → NP_001230855.1  MAP kinase-activated protein kinase 3

    See identical proteins and their annotated locations for NP_001230855.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein.
    Source sequence(s)
    AC096920, BC068497, BE301676, DB450001
    Consensus CDS
    CCDS2832.1
    UniProtKB/Swiss-Prot
    B5BU67, Q16644
    UniProtKB/TrEMBL
    A8K4K4, B2R8Z2, B5BUJ8
    Related
    ENSP00000396467.1, ENST00000446044.5
    Conserved Domains (1) summary
    cd14172
    Location:39 → 304
    STKc_MAPKAPK3; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3

  3. NM_004635.5 → NP_004626.1  MAP kinase-activated protein kinase 3

    See identical proteins and their annotated locations for NP_004626.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
    Source sequence(s)
    AC096920, BC001662, BE301676, BM848086
    Consensus CDS
    CCDS2832.1
    UniProtKB/Swiss-Prot
    B5BU67, Q16644
    UniProtKB/TrEMBL
    A8K4K4, B2R8Z2, B5BUJ8
    Related
    ENSP00000350639.2, ENST00000357955.6
    Conserved Domains (1) summary
    cd14172
    Location:39 → 304
    STKc_MAPKAPK3; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    50611520..50649291
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047448883.1 → XP_047304839.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

  2. XM_047448887.1 → XP_047304843.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

  3. XM_047448884.1 → XP_047304840.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

  4. XM_047448885.1 → XP_047304841.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

  5. XM_047448886.1 → XP_047304842.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    50641158..50679247
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054347797.1 → XP_054203772.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

  2. XM_054347798.1 → XP_054203773.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644

  3. XM_054347799.1 → XP_054203774.1  MAP kinase-activated protein kinase 3 isoform X1

    UniProtKB/Swiss-Prot
    B5BU67, Q16644
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q16644.1 GenPept UniProtKB/Swiss-Prot:Q16644

Gene LinkOut

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