InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DDIT3

Summary

InnateDB Protein

IDBP-603073.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DDIT3

Protein Name

DNA-damage-inducible transcript 3

Synonyms

CEBPZ; CHOP; CHOP-10; CHOP10; GADD153;

Species

Homo sapiens

Ensembl Protein

ENSP00000447188

InnateDB Gene

IDBG-42805 (DDIT3)

Protein Structure

UniProt Annotation

Function

Multifunctional transcription factor in ER stress response. 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. Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes. 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. Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L. 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). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity. 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. {ECO:0000269PubMed:15322075, ECO:0000269PubMed:15775988, ECO:0000269PubMed:16434966, ECO:0000269PubMed:17709599, ECO:0000269PubMed:18940792, ECO:0000269PubMed:19672300, ECO:0000269PubMed:20829347, ECO:0000269PubMed:20876114, ECO:0000269PubMed:22761832}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation.

Disease Associations

Myxoid liposarcoma (MXLIPO) [MIM:613488]: A soft tissue tumor that tends to occur in the limbs (especially the thigh) of patients ranging in age from 35 to 55 years. It is defined by the presence of a hypocellular spindle cell proliferation set in a myxoid background, often with mucin pooling. Lipoblasts tend to be small and often monovacuolated and to cluster around vessels or at the periphery of the lesion. {ECO:0000269PubMed:7503811}. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving DDIT3 has been found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with FUS (PubMed:7503811). {ECO:0000269PubMed:7503811}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 88 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	88 [view]
Protein-Protein	80 [view]
Protein-DNA	8 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003714	transcription corepressor activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0043565	sequence-specific DNA binding

Biological Process

GO:0006355	regulation of transcription, DNA-templated
GO:0006974	cellular response to DNA damage stimulus
GO:0006986	response to unfolded protein
GO:0006987	activation of signaling protein activity involved in unfolded protein response
GO:0007050	cell cycle arrest
GO:0016055	Wnt signaling pathway
GO:0030968	endoplasmic reticulum unfolded protein response
GO:0032757	positive regulation of interleukin-8 production
GO:0034976	response to endoplasmic reticulum stress
GO:0042789	mRNA transcription from RNA polymerase II promoter
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043620	regulation of DNA-dependent transcription in response to stress
GO:0044267	cellular protein metabolic process
GO:0044324	regulation of transcription involved in anterior/posterior axis specification
GO:0045087	innate immune response (InnateDB)
GO:0045454	cell redox homeostasis
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:2000016	negative regulation of determination of dorsal identity