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FLASH GENE
Symbol MAPK1 contributors: mct/shn - updated : 07-09-2014
HGNC name mitogen-activated protein kinase 1
HGNC id 6871
Corresponding disease
DEL22Q11D chromosome 22q11.2 microdeletion syndrome, distal to the DG/VCF typically deleted region
Location 22q11.21      Physical location : 22.113.948 - 22.221.970
Synonym name
  • ERK-2
  • MAP kinase 1
  • MAP kinase 2
  • MAP kinase isoform p42
  • MAPK 2
  • extracellular signal-regulated kinase 2
  • mitogen-activated protein kinase 2
  • p42-MAPK; protein tyrosine kinase ERK2
  • Synonym symbol(s) ERK2, PRKM1, MAPK2, PRKM2, P42MAPK, ERK, ERT1, p41mapk, p38, p40, p41
    EC.number 2.7.11.24
    DNA
    TYPE functioning gene
    STRUCTURE 108.02 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status provisional
    Map cen - D22S427 - D22S446 - MAPK1 - D22S539 - D22S686 - qter
    Physical map
    KIAA1666  KIAA1666 protein HIC2 22q11.21 hypermethylated in cancer 2 LOC220686 22q11.22 hypothetical protein LOC220686 LOC150221 22q11.22 similar to hypothetical protein UBE2L3 22q11.22 ubiquitin-conjugating enzyme E2L 3 LOC150223 22q11.22 hypothetical protein LOC150223 FLJ36046 22q11.22 hypothetical protein FLJ36046 SDF2L1 22q11.22 stromal cell-derived factor 2-like 1 LOC388865 22 similar to RIKEN cDNA 2610318N02 PPIL2 22q11.22 peptidylprolyl isomerase (cyclophilin)-like 2 YPEL1 22q11.2 yippee-like 1 (Drosophila) MAPK1 22q11.2 mitogen-activated protein kinase 1 PPM1F 22q11.22 protein phosphatase 1F (PP2C domain containing) FLJ23185 22q11.22 hypothetical protein FLJ23185 TOP3B 22q11 topoisomerase (DNA) III beta LOC391306 22 similar to Hypothetical protein DJ1198H6.2 IGLVI-70 22q11.2 immunoglobulin lambda variable (I)-70 IGLV4-69 22q11.2 immunoglobulin lambda variable 4-69 IGLVI-68 22q11.2 immunoglobulin lambda variable (I)-68 IGLV10-67 22q11.2 immunoglobulin lambda variable 10-67 IGLVIV-66-1 22q11.2 immunoglobulin lambda variable (IV)-66-1 IGLVV-66 22q11.2 immunoglobulin lambda variable (V)-66 IGLVIV-65 22q11.2 immunoglobulin lambda variable (IV)-65
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 5916 41.4 360 - 2007 17697861
    8 splicing 1499 41 360 - 2007 17697861
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    digestivemouthgingiva   
    Digestivemouthtongue  highly
     salivary gland   highly
    Lymphoid/Immunelymph node   highly
    Nervousbrainforebrain  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an ATP binding site
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Mapk1, Rattus norvegicus
    ortholog to Mapk1, Ms musculus
    ortholog to MAPK1, Pan troglodytes
    intraspecies homolog to MAPK3
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • MAP kinase subfamily
  • CATEGORY enzyme , receptor membrane G serine/threonine kinase
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text
  • translocated to the nucleus after activation where it phosphorylates nuclear targets
  • colocalizes with the WASF2 regulatory complex (WRC) at lamellipodial leading edges and directly phosphorylates two WRC components: WASF2 and ABI1
  • basic FUNCTION
  • phosphorylating nuclear targets, microtubule associated protein 2, myelin basic protein and ELK1
  • promoting entry in the cell cycle
  • activating DD5 and TPR
  • activation of MAPK1 is a key regulator of the increased transition to hypertrophic differentiation of the growth plate
  • may play a critical role in TSC progression through posttranslational inactivation of TSC2 (
  • regulates the proliferation of mesenchymal stem cells without affecting their mobilization and differentiation potential
  • MAPK1/MAPK3 have a crucial role in cardiac hypertrophy
  • plays essential roles in osteoblast differentiation and in supporting osteoclastogenesis
  • MAPK3 and MAPK1 drastically differ in their capability of crossing the nuclear envelope with MAPK3 being three times slower than MAPK1
  • plays a key role in the regulation of apoptosis during retinal development (
  • coordinates adhesion disassembly with WASF2 regulatory complex activation and actin polymerization to promote productive leading edge advancement during cell migration
  • mitophagy in mammalian cells predominantly occurs through an alternative autophagy pathway, requiring the MAPK1 and MAPK14 signaling pathways
  • CELLULAR PROCESS cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    MAPK1/MAPK3 signaling in the neural crest is imperative for normal craniofacial development
    a component
  • components of the two MAPK cascades, MAP3K5-MAP2K4-MAPK10 and RAF1-MAPK1-MAP2K1 interacting with arrestins
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • Mg2+
  • ATP
  • protein
  • ELK1 member of ETS oncogene family, ELK1 (
  • p75 nerve growth factor receptors (
  • vav 1 guanine nucleotide exchange factor, VAV1 (
  • AP kinase-interacting kinase 1 Mnk1 and Mnk2 (
  • MAP kinase phosphatase 3, MKP3 (
  • PYST2dual specificity protein phosphatase PYST2 (
  • PTP-SL and STEP (
  • p90 ribosomal S6 kinase RSK1, RSK2 and RSK3 (
  • topoisomerase IIalpha proteins (
  • phosphorylates beta-arrestin1 (
  • mitogen-activated protein kinase 5, MPK5
  • HePTP (
  • MEK kinase 1, MEKK1 (
  • signal transducer and activator of transcription 5, STAT5 (
  • Histone deacetylase 4, HDAC4 (
  • MAPK/ERK kinase 1, MEK1 and MAPK/ERK kinase 2, MEK2 (
  • Mitogen-activated protein (MAP) kinase phosphatase 1, MKP-1/CL100
  • synuclein and Elk-1 (
  • ceramide (
  • p53 (
  • insulin receptor, IR (
  • AP-1 dimers composed of diverse Jun and Fos family proteins (
  • phosphoprotein enriched in astrocytes 15, PEA15
  • hyaluronan binding protein 1, HABP1 (
  • NGFI-B (
  • 9-cis retinoid X receptor alpha, RXR alpha (
  • estrogen receptor alpha, Era (
  • transducer of ERBB2, TOB (
  • nuclear assembly factor 1 homolog (S. cerevisiae), NAF1 (
  • immediately early gene X-1, IEX-1 (
  • caveolin-1, CAV1 (
  • epidermal growth factor receptor, EGFR (
  • E3 identified by differential display, EDD (
  • MAP kinase Mxi2 (
  • inhibits caspase-9 activity by direct phosphorylation (
  • MAPK phosphatase-7, MKP-7 (
  • RSK1 (
  • paxillin, PXN (
  • LIM-only protein FHL2 in cardiomyocytes (
  • Polo-like kinase-3, Plk3 (
  • vinexin beta (
  • NIMA (never in mitosis gene a)-related kinase 2a, Nek2A (
  • FGFR-signaling adaptor SNT2 (
  • p21 protein (Cdc42/Rac)-activated kinase 1, PAK1 (
  • death-associated protein kinase, DAPK (
  • dual specificity phosphatase 5, DUSP5 (
  • dual specificity protein phosphatase PAC-1 (
  • cell division cycle 25 homolog C (S. pombe), CDC25C (
  • progesterone receptor, PR and MSK1(
  • death effector domain, DED (
  • class II, major histocompatibility complex transactivator, CIITA (
  • HIF1A is a substrate for MAPK1
  • HSPA8 is a potential interacting protein of MAPK1
  • MAPK1 phosphorylates PARD3 and inhibits its binding with KIF3A, thereby controlling PARD3 transport and neuronal polarity
  • PRKCDBP facilitates signal transduction to MAPK1 by anchoring caveolae to the membrane skeleton of the plasma membrane via MYO1C
  • cell & other
    REGULATION
    activated by IL-3
    MAP2K1, MAP2K2
    phosphorylation by TGFB1
    erythropoietin receptor, Epor (
    dephosphorylated and inactivated by VH1-related, VHR (
    Deleted in colorectal cancer, Dcc (
    activated and dephosphorylated by HVH2
    angiotensin AT1a and vasopressin V2 receptors (
    Leukotactin-1, Lkn-1 (
    Tissue plasminogen activator, tPA (
    inhibited by increased levels of p67 (
    protein tyrosine phosphatase epsilon, PTP epsilon (
    ceramide (
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL22Q11D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional somatic mutation      
    Thr188 phosphorylation initiates hypertrophy in cardiomyocytes and is present in failing human hearts
    Susceptibility
    Variant & Polymorphism
    Candidate gene for low birth weight in distal 22q11.2 deletion syndrome
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    knockout studies including MAPK1 revealed some
  • associations with abnormal placental development, leading
  • to intrauterine growth restriction and intrauterine
    death of null mice
  • disrupted Mapk1/mapk3 in mouse granulosa cells provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization
  • double knock-out newborn pups for Erk1 and Erk2 survived for not more one day, appeared normal just after parturition, displayed intracerebral hemorrhages with varying location and severity, ventricular zones and corpus callosum did not develop properly and nuclear morphology in some brain regions were markedly aberrant (
  • double knock-out mice deficient for Erk2 in the central nervous system, with ubiquitous homozygous deletion of Erk1 were neonatally lethal (