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

    Gene ID: 7867, updated on 28-Oct-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
    mouse all
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    Genomic context

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    See MAPKAPK3 in Genome Data Viewer
    Location:
    3p21.2
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (50611520..50649291)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (50641158..50679247)
    RS_2024_09 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 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. 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. Sithanandam G, et al. Mol Cell Biol, 1996 Mar. PMID 8622688, Free PMC Article
    2. Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. McLaughlin MM, et al. J Biol Chem, 1996 Apr 5. PMID 8626550
    3. Gene activity changes in ischemically preconditioned rabbit heart gene: discovery array study. Simkhovich BZ, et al. Heart Dis, 2002 Mar-Apr. PMID 11975836
    4. 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
    5. Mitogen-activated 3p kinase is active in the nucleus. Zakowski V, et al. Exp Cell Res, 2004 Sep 10. PMID 15302577

    See all (62) 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
    		Compare labs

    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 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 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 chromatin remodeling 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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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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    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_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_2024_08

    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

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