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MGP000807

UniProt Annotations

Entry Information
Gene NameDNA-damage-inducible transcript 3
Protein Entry
UniProt IDQ53YD1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P35638-1; Sequence=Displayed; Name=2; IsoId=P35638-2; Sequence=VSP_047277;
DiseaseMyxoid 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:0000269|PubMed: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:0000269|PubMed:7503811}.
DomainThe N-terminal region is necessary for its proteasomal degradation, transcriptional activity and interaction with EP300/P300.
FunctionMultifunctional 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:0000269|PubMed:15322075, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16434966, ECO:0000269|PubMed:17709599, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:19672300, ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:20876114, ECO:0000269|PubMed:22761832}.
InductionBy oxidative stress, amino-acid deprivation, hypoxia and ER stress. During ER stress, induced by a EIF2AK3/ATF4 pathway and/or ERN1/ATF6 pathway. Expression is suppressed by TLR-TRIF signaling pathway during prolonged ER stress. {ECO:0000269|PubMed:19855386, ECO:0000269|PubMed:20829347}.
PtmPhosphorylation at serine residues by MAPK14 enhances its transcriptional activation activity while phosphorylation at serine residues by CK2 inhibits its transcriptional activation activity. {ECO:0000250}.
PtmUbiquitinated, leading to its degradation by the proteasome. {ECO:0000269|PubMed:17872950}.
Sequence CautionSequence=AAB27103.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
SimilarityBelongs to the bZIP family. {ECO:0000305}.
SimilarityContains 1 bZIP (basic-leucine zipper) domain. {ECO:0000255|PROSITE-ProRule:PRU00978}.
Subcellular LocationCytoplasm. Nucleus. Note=Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation.
SubunitHeterodimer. Interacts with TCF7L2/TCF4, EP300/P300, HDAC1, HDAC5 and HDAC6. Interacts with TRIB3 which blocks its association with EP300/P300. Interacts with FOXO3, CEBPB and ATF4. {ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16434966, ECO:0000269|PubMed:17872950, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:22761832}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DDIT3ID80.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ddit3/";
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