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FLASH GENE
Symbol MAPK4 contributors: mct - updated : 28-11-2012
HGNC name mitogen-activated protein kinase 4
HGNC id 6878
Location 18q21.2      Physical location : 48.086.483 - 48.258.195
Synonym name
  • extracellular signal-regulated kinase 3 (p63)
  • Erk3-related
  • MAP kinase isoform p63
    • Synonym symbol(s) PRKM4, ERK3, Erk4, p63MAPK, ERK-4
    EC.number 2.7.1.37, 2.7.11.24
    DNA
    TYPE functioning gene
    STRUCTURE 171.71 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map cen - D18S1101 - (D18S1160 , D18S475 ) - D18S454 - (D18S460 , D18S72 ) - (D18S470 , MAPK4 , D18S474 , D18S69 ) - (D18S486 , D18S58 ) - MBP - (D18S554 , D18S70 ) - qter
    Authors Yoshikawa (97)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 4736 - 587 - 2006 16973613
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Endocrineparathyroid   highly
    Hearing/Equilibriumear   highly
    Nervousbrain    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a Thr-Xxx-Tyr motif in the activation loop, which is catalyzed by members of the MAP kinase kinase family
  • canonical TXY motif within the activation loop of the classical MAPKs is replaced by SEG
  • C-terminal extension responsible for its association with intact cyclin D3
  • a novel MAPKAPK5 interaction motif (FRIEDE) within MAPK7, and MAPK4 essential for binding to the C-terminal region of MAPKAPK5, located within the L16 extension lying C-terminal to the CD (common docking) domain
    • HOMOLOGY
    intraspecies paralog to MAPK7
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • mitogen-activated protein (MAP) kinase family
    • CATEGORY receptor membrane tyrosine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • shuttle between the cytoplasm and the nucleus, and selective inhibition of class I Pak kinase activity in cells promoted increased nuclear accumulation of MAPK4
    • basic FUNCTION
  • phosphorylating microtubule-associated protein 2 (MAP2)
  • may promote entry in the cell cycle
  • atypical mitogen-activated protein kinase having a role in in cell proliferation
  • its function is essential for neonatal survival and critical for the establishment of fetal growth potential and pulmonary function
  • MAPK4 and MAPK7 have acquired specialized functions through evolutionary diversification
  • is a novel class I PAK substrate, further suggesting a role for PAK kinase activity in atypical MAPK signaling
  • role in promoting lung cancer cell invasiveness by phosphorylating NCOA3 and regulating NCOA3 proinvasive activity by site-specific phosphorylation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • novel PAK-MAPK4/MAPK7-MAPKAPK5 signaling pathway
    • a component
  • activation loop phosphorylation of MAPK4 and MAPK6 stimulates their intrinsic catalytic activity and is required for the formation of stable active complexes with MAPKAPK5 and, consequently, for efficient cytoplasmic redistribution of MAPK4/MAPK6/MAPKAPK5 complexes
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CCND3
  • MAPK4, an atypical mitogen-activated protein kinase (MAPK), ias a specific binding partner of CDC14A
  • intimate functional relationship between the CDC14A phosphatase and the MAPK4 in signaling pathways that regulate key cell-fate decisions in human cells
  • potential PAK2 substrate
    • cell & other
    REGULATION
    Phosphorylated by PAK1, PAK2, PAK3 on Ser-189
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    highly upregulated in lung carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    may be an attractive target for therapeutic treatment of invasive lung cancer
    ANIMAL & CELL MODELS
  • loss of Erk3 in mouse retards intrauterine growth, as reflected by a marked reduction in fetal lung, heart, and liver weights, and by low body weight at birth