InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ddit3

Summary

InnateDB Protein

IDBP-194882.6

Last Modified

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

Gene Symbol

Ddit3

Protein Name

DNA-damage inducible transcript 3

Synonyms

chop; CHOP-10; CHOP10; gadd153;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000026475

InnateDB Gene

IDBG-194880 (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. Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling. {ECO:0000269PubMed:12706815, ECO:0000269PubMed:14684614, ECO:0000269PubMed:1547942, ECO:0000269PubMed:15601821, ECO:0000269PubMed:15775988, ECO:0000269PubMed:16670335, ECO:0000269PubMed:19752026, ECO:0000269PubMed:19919955, ECO:0000269PubMed:21159964, ECO:0000269PubMed:22242125, ECO:0000269PubMed:22265908}.

Subcellular Localization

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

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.
They are also associated with 57 interaction(s) predicted by orthology.

Experimentally validated
Total	5 [view]
Protein-Protein	4 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	57 [view]

Gene Ontology

Molecular Function

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

Biological Process

GO:0001955	blood vessel maturation
GO:0006355	regulation of transcription, DNA-templated
GO:0006915	apoptotic process
GO:0006983	ER overload response
GO:0006986	response to unfolded protein
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:0042594	response to starvation
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:0043525	positive regulation of neuron apoptotic process
GO:0044324	regulation of transcription involved in anterior/posterior axis specification
GO:0045454	cell redox homeostasis
GO:0045662	negative regulation of myoblast differentiation
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:0051209	release of sequestered calcium ion into cytosol
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