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

    Gene ID: 7867, updated on 8-Apr-2018
    Official Symbol
    MAPKAPK3provided by HGNC
    Official Full Name
    mitogen-activated protein kinase-activated protein kinase 3provided by HGNC
    Primary source
    HGNC:HGNC:6888
    See related
    Ensembl:ENSG00000114738 MIM:602130; Vega:OTTHUMG00000156850
    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; 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
    Location:
    3p21.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 3 NC_000003.12 (50611862..50649297)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (50649293..50686728)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene VISTA enhancer hs1747 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

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
      Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
    • Cellular Senescence, organism-specific biosystem (from REACTOME)
      Cellular Senescence, organism-specific biosystemCellular senescence involves irreversible growth arrest accompanied by phenotypic changes such as enlarged morphology, reorganization of chromatin through formation of senescence-associated heterochr...
    • Cellular responses to stress, organism-specific biosystem (from REACTOME)
      Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
    • Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation, organism-specific biosystem (from WikiPathways)
      Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation, organism-specific biosystemThis pathway describes the Fas induced apoptosis and interplay with Hsp27 in response to stress. More info: [http://www.biocarta.com/pathfiles/h_hsp27Pathway.asp BioCarta].
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • MAP kinase activation in TLR cascade, organism-specific biosystem (from REACTOME)
      MAP kinase activation in TLR cascade, organism-specific biosystemThe mitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascad...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MyD88 cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88 cascade initiated on plasma membrane, organism-specific biosystemMammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of...
    • MyD88 dependent cascade initiated on endosome, organism-specific biosystem (from REACTOME)
      MyD88 dependent cascade initiated on endosome, organism-specific biosystemUpon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I ...
    • MyD88-independent TLR3/TLR4 cascade, organism-specific biosystem (from REACTOME)
      MyD88-independent TLR3/TLR4 cascade, organism-specific biosystemMyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from ...
    • MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystemThe first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also b...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Oxidative Stress Induced Senescence, organism-specific biosystem (from REACTOME)
      Oxidative Stress Induced Senescence, organism-specific biosystemOxidative stress, caused by increased concentration of reactive oxygen species (ROS) in the cell, can happen as a consequence of mitochondrial dysfunction induced by the oncogenic RAS (Moiseeva et al...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by VEGF, organism-specific biosystem (from REACTOME)
      Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
    • Signaling mediated by p38-alpha and p38-beta, organism-specific biosystem (from Pathway Interaction Database)
      Signaling mediated by p38-alpha and p38-beta, organism-specific biosystem
      Signaling mediated by p38-alpha and p38-beta
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Signalling to ERKs, organism-specific biosystem (from REACTOME)
      Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
    • Signalling to RAS, organism-specific biosystem (from REACTOME)
      Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...
    • TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystem (from REACTOME)
      TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystemTRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.
    • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
      TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
    • Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystemLittle is known about TLR10 ligands. It has been established that the receptor homodimerizes upon binding and signals in an MyD88-dependent manner (Hasan U et al 2005; Nyman T et al 2008). It may als...
    • Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystemTLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at le...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
    • Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystemTLR5 is the receptor for flagellin, the protein that forms bacterial flagella. Unlike most other Pathogen-Associated Molecular Patterns (PAMPs), flagellin does not undergo any posttranslational modif...
    • Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystemRNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich...
    • Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystemCpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated....
    • Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystemTLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial...
    • Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystemTLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recog...
    • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
      Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
    • VEGF signaling pathway, organism-specific biosystem (from KEGG)
      VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGF signaling pathway, conserved biosystem (from KEGG)
      VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
      VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
    • activated TAK1 mediates p38 MAPK activation, organism-specific biosystem (from REACTOME)
      activated TAK1 mediates p38 MAPK activation, organism-specific biosystemp38 mitogen-activated protein kinase (MAPK) belongs to a highly conserved family of serine/threonine protein kinases. The p38 MAPK-dependent signaling cascade is activated by pro-inflammatory or stre...
    • p38 signaling mediated by MAPKAP kinases, organism-specific biosystem (from Pathway Interaction Database)
      p38 signaling mediated by MAPKAP kinases, organism-specific biosystem
      p38 signaling mediated by MAPKAP kinases
    • p38MAPK events, organism-specific biosystem (from REACTOME)
      p38MAPK events, organism-specific biosystemNGF induces sustained activation of p38, a member of the MAPK family (Morooka T, Nishida E, 1998). Both p38 and the ERKs appear to be involved in neurite outgrowth and differentiation caused by NGF i...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    MAP kinase kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    calcium-dependent protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    calmodulin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    calmodulin-dependent protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    mitogen-activated protein kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein serine/threonine kinase activity EXP
    Inferred from Experiment
    more info
    PubMed 
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    Ras protein signal transduction TAS
    Traceable Author Statement
    more info
     
    activation of MAPK activity TAS
    Traceable Author Statement
    more info
     
    cell surface receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    macropinocytosis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    peptidyl-serine phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein autophosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    response to cytokine IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    response to cytokine IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to lipopolysaccharide ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    toll-like receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    toll-like receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    vascular endothelial growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    nucleus TAS
    Traceable Author Statement
    more info
    PubMed 
    Preferred Names
    MAP kinase-activated protein kinase 3
    Names
    MAPK-activated protein kinase 3
    MAPKAP kinase 3
    chromosome 3p kinase
    NP_001230854.1
    NP_001230855.1
    NP_004626.1

    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
      5001..42436
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243925.1NP_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
      Q16644
      UniProtKB/TrEMBL
      A0A024R2W7
      Related
      ENSP00000478922.1, ENST00000621469.4
      Conserved Domains (1) summary
      cd14172
      Location:39304
      STKc_MAPKAPK3; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3
    2. NM_001243926.1NP_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
      Q16644
      UniProtKB/TrEMBL
      A0A024R2W7
      Related
      ENSP00000396467.1, OTTHUMP00000210806, ENST00000446044.5, OTTHUMT00000346237
      Conserved Domains (1) summary
      cd14172
      Location:39304
      STKc_MAPKAPK3; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3
    3. NM_004635.4NP_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
      Q16644
      UniProtKB/TrEMBL
      A0A024R2W7
      Related
      ENSP00000350639.2, OTTHUMP00000210805, ENST00000357955.6, OTTHUMT00000346236
      Conserved Domains (1) summary
      cd14172
      Location:39304
      STKc_MAPKAPK3; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p12 Primary Assembly

      Range
      50611862..50649297
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_940501.2 RNA Sequence

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