Hmdb loader
HMDB Protein ID HMDBP14618
Secondary Accession Numbers None
Name DNA damage-inducible transcript 3 protein
  1. DDIT-3
  2. C/EBP zeta
  3. C/EBP-homologous protein
  4. C/EBP-homologous protein 10
  5. CCAAT/enhancer-binding protein homologous protein
  6. Growth arrest and DNA damage-inducible protein GADD153
  7. CHOP
  8. CHOP-10
Gene Name DDIT3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Multifunctional transcription factor in endoplasmic reticulum (ER) stress response (PubMed:15322075, PubMed:15775988, PubMed:19672300). Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress (PubMed:15322075, PubMed:15775988). Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes (By similarity). Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes (By similarity). Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L (PubMed:15775988, PubMed:17709599, PubMed:22761832, PubMed:20876114). Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG) (PubMed:18940792, PubMed:19672300, PubMed:20829347). Together with ATF4, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity (PubMed:16434966). Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response (By similarity). Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling (By similarity).
  • Alzheimer disease
  • Amyotrophic lateral sclerosis
  • Apoptosis
  • Lipid and atherosclerosis
  • MAPK signaling pathway
  • Non-alcoholic fatty liver disease
  • Parkinson disease
  • Pathways of neurodegeneration - multiple diseases
  • Prion disease
  • Protein processing in endoplasmic reticulum
  • Transcriptional misregulation in cancer
Reactions Not Available
GO Classification
Biological Process
sensory perception of sound
cell redox homeostasis
negative regulation of sequence-specific DNA binding transcription factor activity
negative regulation of interferon-gamma production
positive regulation of interleukin-8 production
cell cycle arrest
negative regulation of fat cell differentiation
negative regulation of protein kinase B signaling cascade
positive regulation of intrinsic apoptotic signaling pathway
regulation of autophagy
response to DNA damage stimulus
response to starvation
endoplasmic reticulum unfolded protein response
release of sequestered calcium ion into cytosol
Wnt receptor signaling pathway
regulation of transcription from RNA polymerase II promoter
positive regulation of sequence-specific DNA binding transcription factor activity
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
negative regulation of NF-kappaB transcription factor activity
negative regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent
negative regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
establishment of protein localization to mitochondrion
anterior/posterior axis specification
response to unfolded protein
negative regulation of canonical Wnt receptor signaling pathway
ATF6-mediated unfolded protein response
blood vessel maturation
ER overload response
intrinsic apoptotic signaling pathway in response to nitrosative stress
negative regulation of CREB transcription factor activity
negative regulation of interleukin-17 production
negative regulation of interleukin-4 production
negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding
PERK-mediated unfolded protein response
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
regulation of transcription from RNA polymerase II promoter in response to stress
regulation of transcription, DNA-dependent
proteasomal ubiquitin-dependent protein catabolic process
positive regulation of neuron apoptotic process
negative regulation of myoblast differentiation
negative regulation of cold-induced thermogenesis
negative regulation of determination of dorsal identity
response to endoplasmic reticulum stress
Cellular Component
protein-DNA complex
CHOP-ATF3 complex
CHOP-ATF4 complex
CHOP-C/EBP complex
late endosome
transcription factor complex
Molecular Function
sequence-specific DNA binding transcription factor activity
DNA-binding transcription activator activity, RNA polymerase II-specific
cAMP response element binding protein binding
transcription factor binding
transcription regulator inhibitor activity
protein homodimerization activity
leucine zipper domain binding
DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II core promoter proximal region sequence-specific DNA binding
transcription regulatory region sequence-specific DNA binding
DNA binding
protein heterodimerization activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 169
Molecular Weight 19174.65
Theoretical pI 4.615
Pfam Domain Function Not Available
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P35638
UniProtKB/Swiss-Prot Entry Name DDIT3_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
General References
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  6. Rabbitts TH, Forster A, Larson R, Nathan P: Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet. 1993 Jun;4(2):175-80. [PubMed:7503811 ]
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  8. Yamaguchi H, Wang HG: CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004 Oct 29;279(44):45495-502. doi: 10.1074/jbc.M406933200. Epub 2004 Aug 18. [PubMed:15322075 ]
  9. Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H: TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J. 2005 Mar 23;24(6):1243-55. doi: 10.1038/sj.emboj.7600596. Epub 2005 Mar 10. [PubMed:15775988 ]
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  12. Su N, Kilberg MS: C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J Biol Chem. 2008 Dec 12;283(50):35106-17. doi: 10.1074/jbc.M806874200. Epub 2008 Oct 21. [PubMed:18940792 ]
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