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Protein

DNA damage-inducible transcript 3 protein

Gene

Ddit3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.11 Publications

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:109247. 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14S → A: Loss of phosphorylation. 1 Publication1
Mutagenesisi15S → A: Loss of phosphorylation. 1 Publication1
Mutagenesisi30S → A: Loss of phosphorylation. 1 Publication1
Mutagenesisi31S → A: Loss of phosphorylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2146304.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766431 – 168DNA damage-inducible transcript 3 proteinAdd BLAST168

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14Phosphoserine; by CK21 Publication1
Modified residuei15Phosphoserine; by CK21 Publication1
Modified residuei30Phosphoserine; by CK21 Publication1
Modified residuei31Phosphoserine; by CK21 Publication1
Modified residuei78Phosphoserine; by MAPK141 Publication1
Modified residuei81Phosphoserine; by MAPK141 Publication1

Post-translational modificationi

Ubiquitinated, leading to its degradation by the proteasome.HMP:
Phosphorylation at serine residues by MAPK14 enhances its transcriptional activation activity while phosphorylation at serine residues by CK2 inhibits its transcriptional activation activity.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP35639.
PaxDbiP35639.
PRIDEiP35639.

PTM databases

iPTMnetiP35639.
PhosphoSitePlusiP35639.

Expressioni

Inductioni

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.6 Publications

Gene expression databases

BgeeiENSMUSG00000025408.
CleanExiMM_DDIT3.
ExpressionAtlasiP35639. baseline and differential.
GenevisibleiP35639. MM.

Interactioni

Subunit structurei

Heterodimer. Interacts with TCF7L2/TCF4, EP300/P300, HDAC5 and HDAC6. Interacts with TRIB3 which blocks its association with EP300/P300. Interacts with FOXO3, CEBPB and ATF4 (By similarity). Interacts with HDAC1.HMP:1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Atf4Q065073EBI-10636142,EBI-77383

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199078. 2 interactors.
DIPiDIP-60705N.
IntActiP35639. 1 interactor.
STRINGi10090.ENSMUSP00000026475.

Chemistry databases

BindingDBiP35639.

Structurei

3D structure databases

ProteinModelPortaliP35639.
SMRiP35639.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini98 – 161bZIPIEP:Add BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni10 – 26N-terminalHMP:Add BLAST17
Regioni10 – 18Interaction with TRIB3HMP:9
Regioni100 – 129Basic motifIEP:Add BLAST30
Regioni133 – 147Leucine-zipperIEP:Add 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.HMP:

Sequence similaritiesi

Belongs to the bZIP family.IKR:

Phylogenomic databases

eggNOGiENOG410ISXY. Eukaryota.
ENOG41127XB. LUCA.
GeneTreeiENSGT00390000006305.
HOGENOMiHOG000089934.
HOVERGENiHBG051328.
InParanoidiP35639.
KOiK04452.
OMAiWELEAWY.
OrthoDBiEOG091G0UKC.
PhylomeDBiP35639.
TreeFamiTF105006.

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.

Sequencei

Sequence statusi: Complete.

P35639-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAESLPFTL ETVSSWELEA WYEDLQEVLS SDEIGGTYIS SPGNEEEESK
60 70 80 90 100
TFTTLDPASL AWLTEEPGPT EVTRTSQSPR SPDSSQSSMA QEEEEEEQGR
110 120 130 140 150
TRKRKQSGQC PARPGKQRMK EKEQENERKV AQLAEENERL KQEIERLTRE
160
VETTRRALID RMVSLHQA
Length:168
Mass (Da):19,189
Last modified:June 1, 1994 - v1
Checksum:iCA423B79512F33AB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti34I → N in AAH13718 (PubMed:15489334).IKR:1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67083 mRNA. Translation: CAA47465.1.
BC013718 mRNA. Translation: AAH13718.1.
CCDSiCCDS24236.1.
PIRiS26148.
RefSeqiNP_001277112.1. NM_001290183.1.
NP_031863.3. NM_007837.4.
XP_006513260.1. XM_006513197.3.
UniGeneiMm.110220.

Genome annotation databases

EnsembliENSMUST00000026475; ENSMUSP00000026475; ENSMUSG00000025408.
GeneIDi13198.
KEGGimmu:13198.
UCSCiuc007hiy.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiDDIT3_MOUSE
AccessioniPrimary (citable) accession number: P35639
Secondary accession number(s): Q91YW9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: October 25, 2017
This is version 144 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families