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FLASH GENE
Symbol GADD45A contributors: mct - updated : 17-08-2013
HGNC name growth arrest and DNA-damage-inducible, alpha
HGNC id 4095
Location 1p31.3      Physical location : 68.150.882 - 68.154.019
Synonym name DNA damage-inducible transcript 1
Synonym symbol(s) DDIT1, GADD45, GA45
DNA
TYPE functioning gene
STRUCTURE 3.16 kb     4 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (CAAT box)
MAPPING cloned   linked N status provisional
Physical map
JAK1 1p31.3 Janus kinase 1 (a protein tyrosine kinase) LOC391045 1 similar to Solute carrier family 2, facilitated glucose transporter, member 3 (Glucose transporter type 3, brain) MRPS21P1 1p31.3 mitochondrial ribosomal protein S21 pseudogene AK3 1p31 adenylate kinase 3 DNAJC6 1pter-q31.3 DnaJ (Hsp40) homolog, subfamily C, member 6 LEPR 1p31 leptin receptor PDE4B 1p31 phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila) DKFZp761D221 1p31.3 hypothetical protein DKFZp761D221 FLJ40873 1p31.3 hypothetical protein FLJ40873 INSL5 1p31.1-p22.3 insulin-like 5 FLJ23129 1p31.3 hypothetical protein FLJ23129 MI-ER1 1p31.3 mesoderm induction early response 1 SLC35D1 1p32-p31 solute carrier family 35 (UDP-glucuronic acid/UDP-N-acetylgalactosamine dual transporter), member D1 IL23R 1p31.3-p31.2 interleukin-23 receptor IL12RB2 1p31.3-p31.2 interleukin 12 receptor, beta 2 PAI-RBP1 1p31-p22 PAI-1 mRNA-binding protein LOC391046 1 similar to heterogeneous nuclear ribonucleoprotein C isoform b; nuclear ribonucleoprotein particle C1 protein; nuclear ribonucleoprotein particle C2 protein GADD45A 1p31.2-p31.1 growth arrest and DNA-damage-inducible, alpha GNG12 1p33-p31 guanine nucleotide binding protein (G protein), gamma 12 LOC391047 1 similar to NAD-dependent deacetylase sirtuin 5 (SIR2-like protein 5) ARHI 1p31 ras homolog gene family, member I FLJ23091 1p31.2 putative NFkB activating protein 373 LOC149224 1p31.2 similar to 40S ribosomal protein S7 (S8) RPE65 1p31 retinal pigment epithelium-specific protein 65kDa SDP35 1p31.2 cell cycle control protein SDP35 AF357533 1q31.3 thioredoxin 1 pseudogene 6 LOC388639 1 LOC388639 KIAA1365 1p31.2 densin-180 PIN1L 1p31 protein (peptidyl-prolyl cis/trans isomerase) NIMA-interacting 1-like FLJ20331 1p31.2 hypothetical protein FLJ20331 SFRS11 1p31-p21 splicing factor, arginine/serine-rich 11 DKFZP566D1346 1p32.3-p31.3 hypothetical protein DKFZp566D1346 HHLA3 1p31.2 HERV-H LTR-associating 3 CTH 1p31 cystathionase (cystathionine gamma-lyase)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 1398 18 165 - 1999 10022855
3 - 1160 - 60 - 1999 10022855
3 - 1296 - 131 - 1999 10022855
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Endocrineparathyroid   highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone  highly
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, G1
life cycle quiescence
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Gadd45a
Homologene
FAMILY ribosomal protein L7AE/gadd45 family
CATEGORY chaperone/stress
SUBCELLULAR LOCALIZATION     intracellular
intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text
  • displays RNase-sensitive colocalization in nuclear speckles with the RNA helicase p68 and the RNA binding protein SC35
  • predominantly nuclear in myotubes and muscle fibers, suggesting that GADD45A promotes muscle atrophy by altering a process within myonuclei
  • basic FUNCTION . TP53-responsive stress protein activating MEKK4 and the p38/JNK pathway in response to environmental stress
  • inactivating (M phase promoting factor) MPF through interaction with CDC2 but not cyclin B1
  • involved in UV- and methyl methanisulfonate (MMS)-induced G2 arrest
  • mediating G2/M checkpoint
  • modifying DNA accessibility on damaged chromatin and stimulating DNA excision repair
  • pstream modulator of pathophysiological changes observed in preeclampsia
  • play important roles in growth control, maintenance of genomic stability, DNA repair, and apoptosis
  • GADD45A, GADD45B, are important for anti-tumor immune responses
  • plays a pivotal role as a stress sensor that modulates cellular responses to various stress stimuli including oncogenic stress
  • functions as a tumor suppressor in Ras-driven breast tumorigenesis via increasing JNK-mediated apoptosis and MAPK14-mediated senescence
  • functions as either tumor promoter or suppressor, is dependent on the oncogenic stress, and is mediated via distinct signaling pathways
  • plays an essential role in gene-specific active DNA demethylation during adult stem cell differentiation
  • active DNA demethylation occurs at osteogene-specific gene promoters during terminal adult stem cell differentiation and GADD45A plays an essential role in this process
  • plays a role in the nucleus and has the potential to bind to genomic DNA
  • may play a role in the regulation of both rRNA and mRNA transcription by changing the methylation patterns of different types (pol I and II) of promoters
  • role for both GADD45A and GADD45B in myeloid innate immune functions by differential modulation of MAPK14 and MAPK8 signaling in granulocytes compared to macrophages
  • is a critical stress-induced mediator of muscle atrophy
  • represses genes involved in anabolic signaling and energy production, and it induces pro-atrophy genes
  • GADD45A is required for immobilization-induced atrophy
  • by reprogramming muscle gene expression, GADD45A reduces multiple barriers to atrophy and stimulates multiple atrophy mechanisms
  • plays important roles in cell cycle checkpoint, DNA repair and apoptosis
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text negative control of cell growth
    PATHWAY
    metabolism
    signaling
  • role of NAMPT/NAD+/SIRT1 pathway in the regulation of GADD45A expression by controlling the acetylation levels of FOXO3
  • a component
  • LCOR and TRIM28 form a complex with ZNF350 on an intronic binding site in GADD45A gene and a novel site in the fibroblast growth factor 2 (FGF2) gene
  • INTERACTION
    DNA
    RNA
  • stimulating DNA repair pathway
  • binds RNA but not single- or double stranded DNA or methylated DNA
  • small molecule
    protein
  • mediating activation of the stress responsive MEKK4, MAPKKK (MAP3KX)
  • proliferating cell nuclear antigen (PCNA) complex
  • TAF12 recruits GADD45A and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation
  • Aurora A interacts through its N-terminal domain with a region of GADD45A encompassing the site of dimerization
  • target for BRCA1 and TP53
  • associated with a ribonucleoprotein particle (
  • TP53-regulated histone-fold protein known to participate in the regulation of cell proliferation, DNA repair, cell cycle, and apoptosis
  • inverse relationship between NAMPT expression and the regulation of GADD45A gene
  • interplay between FOXO3, SIRT1 and GADD45A is the key for the modulation of several cellular processes, including response to extracellular stress, longevity, and tumor suppression
  • GADD45A is required for atrophy induced by immobilization, fasting, denervation, and ATF4 overexpression
  • MDM2-binding partner, interacting with and stabilizing GADD45A through preventing the ubiquitination and degradation of GADD45A mediated by MDM2
  • dendrin binds to WTIP and GADD45A (WTIP and GADD45A mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podocytes
  • cell & other
    REGULATION
    activated by TP53 protein
    nitric oxide (activates GADD45A expression in a FOXO1-dependent manner)
    induced by BRCA1 through binding of the OCT-1 and CAAT motifs in the promoter region of GADD45A
    Other stimulated by FOXO3A and inducing DNA repair
    FOXO1 regulates nitric oxide-induced GADD45A expression and GADD45A is required for the repair of nitric oxide-damaged DNA
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in preeclamptic placentas compared to non-preeclamptic controls, and correlate with elevated sFLT1
    constitutional     --over  
    in atrophying muscles
    Susceptibility to breast cancer
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS