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DDIT3 (DNA damage inducible transcript 3)

Identity

Other namesCHOP (C/EBP homologous protein)
CHOP-10 (C/EBP homologous protein 10)
GADD153 (Growth arrest and DNA damage inducible gene 153)
C/EBP zeta (CCAAT/enhancer binding protein zeta)
HGNC (Hugo) DDIT3
Location 12q13.1-q13.2
Location_base_pair Starts at 56196638 and ends at 56200567 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Description The gene has 4 exons (94 bp, 48 bp, 167 bp and 586 bp). The start codon is in the exon 3. The total genomic sequence spanning the DDIT3 gene is approx. 3 Kb.
Transcription Transcript lenght: 1,1 Kb.

Protein

 
Description 169 amino acids, 29 Kda. DDIT3 contains a carboxy-terminal region (bZIP) formed by a DNA-binding basic domain and a leucine zipper dimerization domain.
Expression DDIT3 is expressed ubiquitously. It is usually expressed at undetectable levels and its expression is induced by cellular stress.
Localisation Nuclear.
Function DDIT3 does not form homodimers and it functions as a dominant negative C/EBP forming heterodimers with other C/EBP members and preventing their binding to C/EBP sequences in the DNA. DDIT3 is implicated in adipogenesis, erythropoiesis, in the induction of growth arrest and in the endoplasmic reticulum stress response.
Homology DDIT3 belongs to the CCAAT/enhancer binding protein (C/EBP) family of transcription factors and it has been found to have high homology in hamster, rat and mouse.

Mutations

Germinal In the mouse, germine mutation in the ddit3 gene produces a decrease in the programmed cell death induced by perturbation in the endoplasmic reticulum function. On the other hand, while DDIT3 inhibits adipogenesis in 3T3-L1 preadipocytes, transgenic mice expressing DDIT3 from a housekeeping promoter display normal adipogenesis.

Implicated in

Note The DDIT3 gene is implicated in two chromosomal translocations associated to the myxoid liposarcoma (MLS). These fusion proteins generated as a result of chromosomal rearragements are used to monitor diagnosis and treatment.
 
  
Entity t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3.
Disease Myxoid liposarcoma (MLS).
Hybrid/Mutated Gene 9 different types of fusions between the genes FUS and DDIT3 have been reported. The most frequent rearragements join the exons 5, 7 or 8 of FUS with the exon 2 of DDIT3.
Oncogenesis The unequivocally relation between FUS/DDIT3 and the MLS was shown by the generation of a transgenic mouse model expressing FUS/DDIT3 from a housekeeping promoter.
  
Entity t(12;22)(q13;q12) chromosomal translocation. It produces the fusion protein EWS/DDIT3.
Disease Myxoid liposarcoma (MLS).
Hybrid/Mutated Gene 2 different types of fusions between the genes EWS and DDIT3 have been reported. The first one joins the exon 7 of EWS with the exon 2 of DDIT3, while the second one joins the exon 10 of EWS with the exon 2 of DDIT3.
  

Breakpoints

 

External links

Nomenclature
HGNC (Hugo)DDIT3   2726
Entrez_Gene (NCBI)DDIT3  1649  DNA-damage-inducible transcript 3
Cards
AtlasDDIT3ID80
GeneCards (Weizmann)DDIT3
Ensembl (Hinxton)ENSG00000175197 [Gene_View]  DDIT3 [Vega]
AceView (NCBI)DDIT3
Genatlas (Paris)DDIT3
euGene (Indiana)1649
SOURCE (Stanford)NM_004083
Gene Expression (Array Express) ENSG00000175197
Genomic and cartography
GoldenPath (UCSC)DDIT3  -     chr12:56196638-56200567 -  12q13.1-q13.2   [Description]    (hg18-Mar_2006)
EnsemblDDIT3 - 12q13.1-q13.2 [CytoView]
Mapping of homologs : NCBIDDIT3 [Mapview]
OMIM126337   
Gene and transcription
Gene : Genbank (Entrez)AA476561 AI658803 AK316581 AV729744 AY461580
Reference sequence (RefSeq transcript) :SRSNM_004083
Reference transcript : EntrezNM_004083
RefSeq genomic : SRSAC_000055 AC_000144 NC_000012 NT_029419 NW_001838060 NW_925395
RefSeq genomic : EntrezAC_000055 AC_000144 NC_000012 NT_029419 NW_001838060 NW_925395
Consensus coding sequences : CCDS NCBIDDIT3
Cluster EST : UnigeneHs.690217 [ SRS ] Hs.690217 [ NCBI ]
Alternative Splicing : Fast-db (Paris)9297
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP35638 (SRS) P35638 (Expasy) P35638 (Uniprot)
With graphics : InterProP35638
Splice isoforms : VarSplice FASTAP35638(VarSplice FASTA)
Domaine pattern : Prosite (SRS)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domain pattern : Prosite (Expaxy)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domains : Interpro (SRS)bZIP_2    DNA_damage_induc_transcript_3    TF_bZIP   
Domains : Interpro (EBI)bZIP_2    DNA_damage_induc_transcript_3    TF_bZIP   
Related proteins : CluSTrP35638
Domain families : Pfam SRSbZIP_2 (PF07716)   
Domain families : Pfam SangerbZIP_2 (PF07716)   
Domain families : Pfam NCBIpfam07716   
Domain families : Smart EMBLBRLZ (SM00338)  
Blocks (Seattle)P35638
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD00529
Protein Interaction databases
DIP (DOE-UCLA)P35638
IntAct (EBI)P35638
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIDDIT3
SNP : GeneSNP UtahDDIT3
SNP : HGBaseDDIT3
Genetic variants : HAPMAPDDIT3
Cancer Gene: CensusDDIT3 
Somatic Mutations in Cancer : COSMICDDIT3 
Rearrangement : COSMICEWSR1 22q12.2  -  DDIT3 12q13.3
Translocation Breakpoints in Cancer : TICdbDDIT3 
Mutations and Diseases : HGMDDDIT3
Hereditary diseases : OMIM126337   
Hereditary diseases : GENETests126337   
Diseases : Genetic AssociationDDIT3
General knowledge
Homologs : HomoloGeneDDIT3
Homology/Alignments : Family Browser UCSCDDIT3
Phylogenetic Trees/Animal Genes : TreeFamDDIT3
Chemical/Protein Interactions : CTD1649
Keywords Ontology : AmiGOresponse to amphetamine  transcription factor activity  transcription corepressor activity  nucleus  cytoplasm  regulation of transcription, DNA-dependent  response to DNA damage stimulus  response to oxidative stress  ER overload response  cell cycle  cell cycle arrest  aging  response to nutrient  endoplasmic reticulum unfolded protein response  negative regulation of CREB transcription factor activity  response to drug  response to hydrogen peroxide  mRNA transcription from RNA polymerase II promoter  positive regulation of apoptosis  sequence-specific DNA binding  cell redox homeostasis  positive regulation of transcription  protein dimerization activity  embryonic organ development  
Keywords Ontology : EGO-EBIresponse to amphetamine  transcription factor activity  transcription corepressor activity  nucleus  cytoplasm  regulation of transcription, DNA-dependent  response to DNA damage stimulus  response to oxidative stress  ER overload response  cell cycle  cell cycle arrest  aging  response to nutrient  endoplasmic reticulum unfolded protein response  negative regulation of CREB transcription factor activity  response to drug  response to hydrogen peroxide  mRNA transcription from RNA polymerase II promoter  positive regulation of apoptosis  sequence-specific DNA binding  cell redox homeostasis  positive regulation of transcription  protein dimerization activity  embryonic organ development  
Pathways : BIOCARTAp38 MAPK Signaling Pathway [Genes]   
Pathways : KEGGMAPK signaling pathway
Other databases
Probes
Probes : ImagenesDDIT3 Related clones (RZPD - Berlin)
Literature
PubMed90 Pubmed reference(s) in Entrez
PubGeneDDIT3

Bibliography

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Contributor(s)

Written07-2004Pedro A Pérez-Mancera, Isidro Sánchez-Garcìa
Laboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain

Citation

This paper should be referenced as such :
Pérez-Mancera PA, Sánchez-Garcìa I . DDIT3 (DNA damage inducible transcript 3). Atlas Genet Cytogenet Oncol Haematol. July 2004 .
URL : http://AtlasGeneticsOncology.org/Genes/DDIT3ID80.html

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