DDIT3 (DNA damage inducible transcript 3)

Identity

Other names	CHOP (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)
Hugo	DDIT3
Location	12q13.1-q13.2

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
Hugo	DDIT3
GDB	DDIT3
Entrez_Gene	DDIT3  1649  DNA-damage-inducible transcript 3
	Cards
Atlas	DDIT3ID80
GeneCards	DDIT3
Ensembl	DDIT3 [Search_View]   ENSG00000175197 [Gene_View]
Genatlas	DDIT3
GeneLynx	DDIT3
eGenome	DDIT3
euGene	1649
	Genomic and cartography
GoldenPath	DDIT3  -     chr12:56196640-56200567 -  12q13.1-q13.2   [Description]    (hg18-Mar_2006)
Ensembl	DDIT3 - 12q13.1-q13.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	DDIT3
	Gene and transcription
Genbank	AA476561 [ ENTREZ ]
Genbank	AI658803 [ ENTREZ ]
Genbank	AK316581 [ ENTREZ ]
Genbank	AV729744 [ ENTREZ ]
Genbank	AY461580 [ ENTREZ ]
RefSeq	NM_004083 [ SRS ]    NM_004083 [ ENTREZ ]
RefSeq	AC_000055 [ SRS ]    AC_000055 [ ENTREZ ]
RefSeq	AC_000144 [ SRS ]    AC_000144 [ ENTREZ ]
RefSeq	NC_000012 [ SRS ]    NC_000012 [ ENTREZ ]
RefSeq	NT_029419 [ SRS ]    NT_029419 [ ENTREZ ]
RefSeq	NW_001838060 [ SRS ]    NW_001838060 [ ENTREZ ]
RefSeq	NW_925395 [ SRS ]    NW_925395 [ ENTREZ ]
AceView	DDIT3 AceView - NCBI
Unigene	Hs.690217 [ SRS ]    Hs.690217 [ NCBI ]     HS690217 [ spliceNest ]
Fast-db	9297 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P35638 [ SRS]    P35638 [ EXPASY ]     P35638 [ INTERPRO ]
Prosite	PS50217 BZIP [ SRS ]    PS50217 BZIP [ Expasy ]
Prosite	PS00036 BZIP_BASIC [ SRS ]    PS00036 BZIP_BASIC [ Expasy ]
Interpro	IPR011700 bZIP_2 [ SRS ]    IPR011700 bZIP_2 [ EBI ]
Interpro	IPR016670 DNA_damage_induc_transcript_3 [ SRS ]    IPR016670 DNA_damage_induc_transcript_3 [ EBI ]
Interpro	IPR004827 TF_bZIP [ SRS ]    IPR004827 TF_bZIP [ EBI ]
CluSTr	P35638
Pfam	PF07716 bZIP_2 [ SRS ]    PF07716 bZIP_2 [ Sanger ]    pfam07716 [ NCBI-CDD ]
Smart	SM00338 BRLZ [EMBL]
Blocks	P35638
PDB	DDIT3 [ SRS ]    DDIT3 [ PdbSum ],   DDIT3 [ IMB ]   DDIT3 [ RSDB ]
HPRD	00529
	Protein Interaction databases
DIP	P35638
IntAct	P35638
	Polymorphism : SNP, mutations, diseases
OMIM	126337    [ map ]
GENECLINICS	126337
SNP	DDIT3 [dbSNP-NCBI]
SNP	NM_004083 [SNP-NCI]
SNP	DDIT3 [GeneSNPs - Utah]  DDIT3] [HGBASE - SRS]
HAPMAP	DDIT3 [HAPMAP]
COSMIC	DDIT3 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	DDIT3 [Translocation breakpoints In Cancer]
HGMD	DDIT3
	General knowledge
Family Browser	DDIT3 [UCSC Family Browser]
SOURCE	NM_004083
SMD	Hs.690217
SAGE	Hs.690217
GO	response to amphetamine [Amigo]  response to amphetamine
GO	transcription factor activity [Amigo]  transcription factor activity
GO	transcription corepressor activity [Amigo]  transcription corepressor activity
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	response to DNA damage stimulus [Amigo]  response to DNA damage stimulus
GO	response to oxidative stress [Amigo]  response to oxidative stress
GO	ER overload response [Amigo]  ER overload response
GO	cell cycle [Amigo]  cell cycle
GO	cell cycle arrest [Amigo]  cell cycle arrest
GO	aging [Amigo]  aging
GO	response to nutrient [Amigo]  response to nutrient
GO	regulation of cell redox homeostasis [Amigo]  regulation of cell redox homeostasis
GO	endoplasmic reticulum unfolded protein response [Amigo]  endoplasmic reticulum unfolded protein response
GO	negative regulation of CREB transcription factor activity [Amigo]  negative regulation of CREB transcription factor activity
GO	response to hydrogen peroxide [Amigo]  response to hydrogen peroxide
GO	mRNA transcription from RNA polymerase II promoter [Amigo]  mRNA transcription from RNA polymerase II promoter
GO	positive regulation of apoptosis [Amigo]  positive regulation of apoptosis
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GO	positive regulation of transcription [Amigo]  positive regulation of transcription
GO	protein dimerization activity [Amigo]  protein dimerization activity
GO	embryonic organ development [Amigo]  embryonic organ development
BIOCARTA	p38 MAPK Signaling Pathway    [Genes]
KEGG	MAPK signaling pathway
PubGene	DDIT3
TreeFam	DDIT3
CTD	1649 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	DDIT3 Related clones (RZPD - Berlin)
	PubMed
PubMed	68 Pubmed reference(s) in LocusLink

Bibliography

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PMID 1339368

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PMID 7503811

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PMID 1547942

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Contributor(s)

Written	07-2004	Pedro A Pérez-Mancera, Isidro Sánchez-Garc&icute;a
		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-García I . DDIT3 (DNA damage inducible transcript 3). Atlas Genet Cytogenet Oncol Haematol. July 2004 . URL : http://AtlasGeneticsOncology.org/Genes/DDIT3ID80.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 17:43:31 2008