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Aliases for DDIT3 Gene

Aliases for DDIT3 Gene

  • DNA-Damage-Inducible Transcript 3 2 3
  • C/EBP Zeta 2 3 4
  • GADD153 3 4 6
  • CHOP10 3 4 6
  • Growth Arrest And DNA Damage-Inducible Protein GADD153 3 4
  • CCAAT/Enhancer-Binding Protein Homologous Protein 3 4
  • C/EBP-Homologous Protein 10 3 4
  • CHOP-10 3 4
  • DDIT-3 3 4
  • CHOP 3 4
  • DNA Damage-Inducible Transcript 3 Protein 3
  • C/EBP-Homologous Protein 4
  • CEBPZ 3

External Ids for DDIT3 Gene

Previous GeneCards Identifiers for DDIT3 Gene

  • GC12M059181
  • GC12M058053
  • GC12M057627
  • GC12M056196
  • GC12M057910
  • GC12M054948

Summaries for DDIT3 Gene

Entrez Gene Summary for DDIT3 Gene

  • This gene encodes a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, such as C/EBP and LAP (liver activator protein), and preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, is activated by endoplasmic reticulum stress, and promotes apoptosis. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in myxoid liposarcomas or Ewing sarcoma. Multiple alternatively spliced transcript variants encoding two isoforms with different length have been identified. [provided by RefSeq, Aug 2010]

GeneCards Summary for DDIT3 Gene

DDIT3 (DNA-Damage-Inducible Transcript 3) is a Protein Coding gene. Diseases associated with DDIT3 include myxoid liposarcoma and myxoid/round cell liposarcoma. Among its related pathways are MAPK signaling pathway and Akt Signaling. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and transcription factor binding.

UniProtKB/Swiss-Prot for DDIT3 Gene

  • 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.

Gene Wiki entry for DDIT3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DDIT3 Gene

Genomics for DDIT3 Gene

Regulatory Elements for DDIT3 Gene

Genomic Location for DDIT3 Gene

Start:
57,516,588 bp from pter
End:
57,520,517 bp from pter
Size:
3,930 bases
Orientation:
Minus strand

Genomic View for DDIT3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for DDIT3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DDIT3 Gene

Proteins for DDIT3 Gene

  • Protein details for DDIT3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35638-DDIT3_HUMAN
    Recommended name:
    DNA damage-inducible transcript 3 protein
    Protein Accession:
    P35638
    Secondary Accessions:
    • F8VS99

    Protein attributes for DDIT3 Gene

    Size:
    169 amino acids
    Molecular mass:
    19175 Da
    Quaternary structure:
    • Heterodimer. 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.
    SequenceCaution:
    • Sequence=AAB27103.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};

    Alternative splice isoforms for DDIT3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DDIT3 Gene

Proteomics data for DDIT3 Gene at MOPED

Post-translational modifications for DDIT3 Gene

  • Phosphorylation at serine residues by MAPK14 enhances its transcriptional activation activity while phosphorylation at serine residues by CK2 inhibits its transcriptional activation activity.
  • Ubiquitinated, leading to its degradation by the proteasome.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for DDIT3 Gene

Domains for DDIT3 Gene

Protein Domains for DDIT3 Gene

Graphical View of Domain Structure for InterPro Entry

P35638

UniProtKB/Swiss-Prot:

DDIT3_HUMAN :
  • P35638
Domain:
  • The N-terminal region is necessary for its proteasomal degradation, transcriptional activity and interaction with EP300/P300
  • Contains 1 bZIP (basic-leucine zipper) domain.
Family:
  • Belongs to the bZIP family.
genes like me logo Genes that share domains with DDIT3: view

No data available for Gene Families for DDIT3 Gene

Function for DDIT3 Gene

Molecular function for DDIT3 Gene

GENATLAS Biochemistry: DDIT3 dominant negative regulator of several C/EBP transcription factors,involved in t(12;16) translocation (see FUS),involved in erythroid growth and differentiation possibly through interaction with both C/EBP and non C/EBP family members
UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction: By 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.

Gene Ontology (GO) - Molecular Function for DDIT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IDA 24939851
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA 22065586
GO:0001077 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IDA 22065586
GO:0003677 DNA binding IDA 14667815
GO:0003700 sequence-specific DNA binding transcription factor activity IGI 24939851
genes like me logo Genes that share ontologies with DDIT3: view
genes like me logo Genes that share phenotypes with DDIT3: view

Animal Models for DDIT3 Gene

MGI Knock Outs for DDIT3:

miRNA for DDIT3 Gene

miRTarBase miRNAs that target DDIT3

Transcription Factor Targeting for DDIT3 Gene

Selected GeneGlobe predicted Target genes for DDIT3
Targeting motifs for DDIT3 Gene
HOMER Transcription Factor Regulatory Elements motif DDIT3
  • Consensus sequence: ATTGCATCAT Submotif: canonical Cell Type: MEF GeoId: GSE35681

No data available for Enzyme Numbers (IUBMB) for DDIT3 Gene

Localization for DDIT3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DDIT3 Gene

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

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for DDIT3 Gene COMPARTMENTS Subcellular localization image for DDIT3 gene
Compartment Confidence
nucleus 5
endoplasmic reticulum 4
cytosol 2
mitochondrion 2
extracellular 1

Gene Ontology (GO) - Cellular Components for DDIT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 11478948
GO:0005654 nucleoplasm TAS --
GO:0005770 late endosome IEA --
GO:0005829 cytosol TAS 14685163
GO:0032993 protein-DNA complex IDA 15322075
genes like me logo Genes that share ontologies with DDIT3: view

Pathways for DDIT3 Gene

genes like me logo Genes that share pathways with DDIT3: view

Gene Ontology (GO) - Biological Process for DDIT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IDA 11478948
GO:0001955 blood vessel maturation IEA --
GO:0006355 regulation of transcription, DNA-templated IMP 17872950
GO:0006915 apoptotic process --
GO:0006974 cellular response to DNA damage stimulus TAS 1339368
genes like me logo Genes that share ontologies with DDIT3: view

Compounds for DDIT3 Gene

(64) Novoseek inferred chemical compound relationships for DDIT3 Gene

Compound -log(P) Hits PubMed IDs
tunicamycin 80.2 13
n-(4-hydroxyphenyl)retinamide 75.8 39
l-(4,5-3h)leucine 71.7 1
thapsigargin 65.6 14
pga2 62.7 7
genes like me logo Genes that share compounds with DDIT3: view

Transcripts for DDIT3 Gene

Unigene Clusters for DDIT3 Gene

DNA-damage-inducible transcript 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for DDIT3 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b · 3c · 3d · 3e · 3f ^ 4a · 4b · 4c · 4d · 4e
SP1: - - - - -
SP2: - - - -
SP3: -
SP4: - -
SP5: - - - - - -
SP6: - - -
SP7: -
SP8: - - - -

Relevant External Links for DDIT3 Gene

GeneLoc Exon Structure for
DDIT3
ECgene alternative splicing isoforms for
DDIT3

Expression for DDIT3 Gene

mRNA expression in normal human tissues for DDIT3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for DDIT3 Gene

SOURCE GeneReport for Unigene cluster for DDIT3 Gene Hs.505777

genes like me logo Genes that share expressions with DDIT3: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for DDIT3 Gene

Orthologs for DDIT3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for DDIT3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DDIT3 35
  • 99.13 (n)
  • 99.48 (a)
DDIT3 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia DDIT3 35
  • 91.87 (n)
  • 93.45 (a)
DDIT3 36
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia DDIT3 35
  • 92 (n)
  • 91.43 (a)
DDIT3 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ddit3 35
  • 87.7 (n)
  • 88.69 (a)
Ddit3 16
Ddit3 36
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ddit3 35
  • 89.29 (n)
  • 91.07 (a)
lizard
(Anolis carolinensis)
Reptilia DDIT3 36
  • 45 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ddit3 35
  • 56.5 (n)
  • 51.83 (a)
zebrafish
(Danio rerio)
Actinopterygii ddit3 36
  • 32 (a)
OneToOne
Species with no ortholog for DDIT3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for DDIT3 Gene

ENSEMBL:
Gene Tree for DDIT3 (if available)
TreeFam:
Gene Tree for DDIT3 (if available)

Paralogs for DDIT3 Gene

No data available for Paralogs for DDIT3 Gene

Variants for DDIT3 Gene

Sequence variations from dbSNP and Humsavar for DDIT3 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs697221 -- 57,517,377(+) GTCCC(A/G)AAGGA reference, synonymous-codon
rs703835 -- 57,517,685(+) TTTGG(A/G)AAAGG intron-variant, utr-variant-5-prime
rs2291136 -- 57,517,188(-) CATTT(A/C)CTTGA intron-variant
rs4760298 -- 57,517,946(+) CTCGG(C/T)CTCCC intron-variant
rs11834654 -- 57,517,820(+) Ttttt(C/T)ttttt intron-variant

Structural Variations from Database of Genomic Variants (DGV) for DDIT3 Gene

Variant ID Type Subtype PubMed ID
nsv899117 CNV Loss 21882294
nsv899118 CNV Gain 21882294
dgv513e1 CNV Complex 17122850
nsv428283 CNV Gain 18775914
nsv469411 CNV Loss 19166990
nsv899119 CNV Loss 21882294
nsv899120 CNV Loss 21882294

Relevant External Links for DDIT3 Gene

HapMap Linkage Disequilibrium report
DDIT3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DDIT3 Gene

Disorders for DDIT3 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (3) Diseases for DDIT3 Gene including...

Search for DDIT3 Gene in MalaCards »

(1) OMIM Diseases for DDIT3 Gene (126337)

UniProtKB/Swiss-Prot

DDIT3_HUMAN
  • 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: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}.

(1) University of Copenhagen DISEASES for DDIT3 Gene

(36) Novoseek inferred disease relationships for DDIT3 Gene

Disease -log(P) Hits PubMed IDs
liposarcoma myxoid 91.3 22
liposarcoma 79.1 20
sarcoma 45.1 6
cancer 39.9 16
lipoma 34.2 2

Genatlas disease for DDIT3 Gene

myxoid liposarcoma,with breakpoint in t(12;16) translocation (see FUS)

Relevant External Links for DDIT3

Genetic Association Database (GAD)
DDIT3
Human Genome Epidemiology (HuGE) Navigator
DDIT3
genes like me logo Genes that share disorders with DDIT3: view

Publications for DDIT3 Gene

  1. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. (PMID: 8510758) Crozat A. … Ron D. (Nature 1993) 3 4 23
  2. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. (PMID: 15322075) Yamaguchi H. … Wang H.G. (J. Biol. Chem. 2004) 3 4 23
  3. The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals. (PMID: 16434966) Horndasch M. … Gloy J. (Oncogene 2006) 3 4 23
  4. Critical and functional regulation of CHOP (C/EBP homologous protein) through the N-terminal portion. (PMID: 17872950) Ohoka N. … Hayashi H. (J. Biol. Chem. 2007) 3 4 23
  5. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. (PMID: 15775988) Ohoka N. … Hayashi H. (EMBO J. 2005) 3 4 23

Products for DDIT3 Gene

  • Addgene plasmids for DDIT3

Sources for DDIT3 Gene

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