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Protein

DNA damage-inducible transcript 3 protein

Gene

Ddit3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processApoptosis, Cell cycle, Growth arrest, Stress response, Transcription, Transcription regulation, Unfolded protein response, Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
DNA damage-inducible transcript 3 protein
Short name:
DDIT-3
Alternative name(s):
C/EBP zeta
C/EBP-homologous protein
Short name:
CHOP
C/EBP-homologous protein 10
Short name:
CHOP-10
CCAAT/enhancer-binding protein homologous protein
Growth arrest and DNA-damage-inducible protein GADD153
Gene namesi
Name:Ddit3
Synonyms:Chop, Chop10, Gadd153
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi62391 Ddit3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3797018

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766441 – 168DNA damage-inducible transcript 3 proteinAdd BLAST168

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14Phosphoserine; by CK2By similarity1
Modified residuei15Phosphoserine; by CK2By similarity1
Modified residuei30Phosphoserine; by CK2By similarity1
Modified residuei31Phosphoserine; by CK2By similarity1
Modified residuei78Phosphoserine; by MAPK14By similarity1
Modified residuei81Phosphoserine; by MAPK14By similarity1

Post-translational modificationi

Ubiquitinated, leading to its degradation by the proteasome.By similarity
Phosphorylation at serine residues by MAPK14 enhances its transcriptional activation activity while phosphorylation at serine residues by CK2 inhibits its transcriptional activation activity.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62857
PRIDEiQ62857

Interactioni

Subunit structurei

Heterodimer (By similarity). 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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

ComplexPortaliCPX-60 CHOP-C/EBPalpha complex
CPX-62 CHOP-C/EBPbeta complex
IntActiQ62857, 3 interactors
STRINGi10116.ENSRNOP00000008941

Structurei

3D structure databases

SMRiQ62857
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini98 – 161bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni10 – 26N-terminalBy similarityAdd BLAST17
Regioni10 – 18Interaction with TRIB3By similarity9
Regioni100 – 129Basic motifPROSITE-ProRule annotationAdd BLAST30
Regioni133 – 147Leucine-zipperPROSITE-ProRule annotationAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi92 – 97Poly-Glu6

Domaini

The N-terminal region is necessary for its proteasomal degradation, transcriptional activity and interaction with EP300/P300.By similarity

Sequence similaritiesi

Belongs to the bZIP family.Curated

Phylogenomic databases

eggNOGiENOG410ISXY Eukaryota
ENOG41127XB LUCA
HOGENOMiHOG000089934
HOVERGENiHBG051328
InParanoidiQ62857
PhylomeDBiQ62857

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR016670 DNA_damage_induc_transcript_3
PANTHERiPTHR16833 PTHR16833, 1 hit
PIRSFiPIRSF016571 C/EBPzeta_CHOP_DDIT3, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q62857-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAAESLPFAF ETVSSWELEA WYEDLQEVLS SDEIGGTYIS SPGNEEEESK
60 70 80 90 100
TFTTLDPASL AWLTEEPGPA EVTSTSQSPR SPDSSQSSMA QEEEEEDQGR
110 120 130 140 150
TRKRKQSGQC AARAGKQRMK EKEQENERKV AQLAEENERL KLEIERLTRE
160
VETTRRALID RMVSLHQA
Length:168
Mass (Da):19,013
Last modified:November 1, 1996 - v1
Checksum:i251716CD712BA6E1
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q496Y7Q496Y7_RAT
DNA damage-inducible transcript 3 p...
Ddit3 rCG_59371
168Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36994 mRNA Translation: AAA87944.1
UniGeneiRn.11183

Genome annotation databases

UCSCiRGD:62391 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36994 mRNA Translation: AAA87944.1
UniGeneiRn.11183

3D structure databases

SMRiQ62857
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-60 CHOP-C/EBPalpha complex
CPX-62 CHOP-C/EBPbeta complex
IntActiQ62857, 3 interactors
STRINGi10116.ENSRNOP00000008941

Chemistry databases

ChEMBLiCHEMBL3797018

Proteomic databases

PaxDbiQ62857
PRIDEiQ62857

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:62391 rat

Organism-specific databases

RGDi62391 Ddit3

Phylogenomic databases

eggNOGiENOG410ISXY Eukaryota
ENOG41127XB LUCA
HOGENOMiHOG000089934
HOVERGENiHBG051328
InParanoidiQ62857
PhylomeDBiQ62857

Miscellaneous databases

PROiPR:Q62857

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR016670 DNA_damage_induc_transcript_3
PANTHERiPTHR16833 PTHR16833, 1 hit
PIRSFiPIRSF016571 C/EBPzeta_CHOP_DDIT3, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDDIT3_RAT
AccessioniPrimary (citable) accession number: Q62857
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 109 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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