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FLASH GENE
Symbol GADD45B contributors: shn/mct - updated : 04-01-2015
HGNC name growth arrest and DNA-damage-inducible, beta
HGNC id 4096
Location 19p13.3      Physical location : 2.476.122 - 2.478.257
Synonym name
  • myeloid differentiation primary response protein MyD118
  • growth arrest and DNA-damage-inducible beta
  • negative growth regulatory protein MyD118
  • Synonym symbol(s) MYD118, GADD45BETA, DKFZP566B133
    DNA
    TYPE functioning gene
    STRUCTURE 2.12 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map pter - D19S883 - D19S878 - GADD45B - D19S565 - D19S591 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1363 - 160 - 2005 16144844
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrinepancreas   highly
    Nervousbrain   lowly
    Reproductivefemale systemplacenta  highly
    Respiratorylung   moderately
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cell lineage myeloid
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • DEDDDR residues may be necessary to regulate the G(2)/M checkpoint
  • HOMOLOGY
    interspecies ortholog to Gadd45b, Rattus norvegicus
    ortholog to Gadd45b, Mus musculus
    ortholog to GADD45B, Pan troglodytes
    ortholog to gadd45b, Danio rerio
    Homologene
    FAMILY
  • GADD45 family
  • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    basic FUNCTION
  • activating MEKK4 and the p38/JNK pathway in response to environmental stress
  • implicated in the stress response, cell cycle arrest, genomic stability, DNA repair, apoptosis, adaptive immune response, and DNA 5-methylcytosine excision in cultured cells
  • plays an essential role during chondrocyte terminal differentiation
  • plays an important role in regulating the cardiac hypertrophy
  • required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes critical for adult neurogenesis
  • has an essential role in activity induced, but not basal, proliferation of neural progenitors in the adult dentate gyrus
  • important component of the intrinsic neuroprotective mechanisms of retinal ganglion cells neurons in the retina and, perhaps in the CNS as well
  • GADD45A, GADD45B, are important for anti-tumor immune responses
  • key player in ischaemia/hypoxia-induced apoptotic cardiomyocyte death
  • positive mediator of apoptosis induced by certain cytokines and oncogenes
  • gene most strongly induced early during both compensatory regeneration and drug-induced hyperplasia
  • role for both GADD45A and GADD45B in myeloid innate immune functions by differential modulation of MAPK14 and MAPK8 signaling in granulocytes compared to macrophages
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, repair
    nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS
    text negative control of cell growth
    PATHWAY
    metabolism
    signaling
    a component
  • enhances COL10A1 transcription via the MTK1/MKK3/6/MAPK14 axis and activation of CEBPB-TAD4 in terminally differentiating chondrocytes
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • mediating activation of stress responsive MEKK4, MAPKKK (MAP3Kx)
  • proliferating cell nuclear antigen (PCNA) complex and cyclin dependent kinase inhibitor 1A (CDKN1A)
  • essential mediator of matrix metalloproteinase-13 (MMP13) expression during terminal chondrocyte differentiation
  • binds to MAP2K7 directly and blocks its catalytic activity, mediates the inhibition of JNK signaling
  • growth arrest and DNA-damage-inducible, gamma (GADD45GIP1)
  • cell cycle-specific kinase cdc2, cyclin B1 kinase (CCNB1) and cdc2/CCNB1 complex
  • nuclear hormone receptors RXR alpha, RAR alpha, ER alpha, PPAR alpha, PPAR beta and PPAR gamma2
  • growth arrest and DNA-damage-inducible, alpha (Gadd45A)
  • CR6-interacting factor 1 (CRIF1)
  • mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2
  • GADD45B enhances activity of the proximal COL10A1 promoter, which contains evolutionarily conserved AP-1, cAMP-response element, and CEBP half-sites, in synergism with CEBP family members
  • direct target for NR1I2, eliciting cell signals to regulate various cellular functions
  • spatial regulation of MAPK14 by GADD45B/MAP3K4 negatively regulates the autophagic process
  • GADD45 proteins bind the JNK kinase mitogen-activated protein kinase kinase 7 (MAP2K7) and inhibit its activity, even under normal physiological conditions
  • cell & other
    REGULATION
    induced by multiple cytokines
    stress
    bone morphogenetic protein-2 (BMP2) through a Smad1/Runx2-dependent pathway
    electroconvulsive treatment (ECT) (Ma et al 2009)
    induced by light in the suprachiasmatic nucleus (Porterfield et al 2007)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    significantly in patients with hypertrophy cardiomyopathy
    tumoral     --over  
    in gastric cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheromacardiac
    its inhibition might be of benefit in the treatment of acute ischaemic heart disease
    ANIMAL & CELL MODELS
  • Mice with Gadd45b deletion exhibit specific deficits in neural activity–induced proliferation of neural progenitors and dendritic growth of newborn neurons in the adult hippocampus (Ma et al 2009)
  • hypertrophic zone of the Gadd45beta(-/-)mouse embryonic growth plate is compressed, and expression of type X collagen (Col10a1) genes is decreased