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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

  • apoptotic process Source: UniProtKB
  • blood vessel maturation Source: UniProtKB
  • cell cycle arrest Source: MGI
  • cell redox homeostasis Source: MGI
  • endoplasmic reticulum unfolded protein response Source: MGI
  • ER overload response Source: MGI
  • establishment of protein localization to mitochondrion Source: ParkinsonsUK-UCL
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to nitrosative stress Source: ParkinsonsUK-UCL
  • mRNA transcription from RNA polymerase II promoter Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of CREB transcription factor activity Source: MGI
  • negative regulation of determination of dorsal identity Source: BHF-UCL
  • negative regulation of DNA binding Source: ParkinsonsUK-UCL
  • negative regulation of fat cell differentiation Source: MGI
  • negative regulation of myoblast differentiation Source: UniProtKB
  • negative regulation of protein kinase B signaling Source: MGI
  • negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • positive regulation of interleukin-8 production Source: MGI
  • positive regulation of neuron apoptotic process Source: UniProtKB
  • positive regulation of neuron death Source: ParkinsonsUK-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription involved in anterior/posterior axis specification Source: BHF-UCL
  • release of sequestered calcium ion into cytosol Source: UniProtKB
  • response to endoplasmic reticulum stress Source: UniProtKB
  • response to starvation Source: UniProtKB
  • response to unfolded protein Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Apoptosis, Cell cycle, Growth arrest, Stress response, Transcription, Transcription regulation, Unfolded protein response, Wnt signaling pathway

Keywords - Ligandi

DNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:109247. Ddit3.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation.

GO - Cellular componenti

  • CHOP-ATF3 complex Source: MGI
  • CHOP-ATF4 complex Source: MGI
  • CHOP-C/EBP complex Source: ParkinsonsUK-UCL
  • cytoplasm Source: ParkinsonsUK-UCL
  • late endosome Source: MGI
  • nucleus Source: UniProtKB
  • protein-DNA complex Source: MGI
  • transcription factor AP-1 complex Source: Ensembl
Complete GO annotation...

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.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.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.By similarity1 Publication

GO - Molecular functioni

  • cAMP response element binding protein binding Source: MGI
  • leucine zipper domain binding Source: MGI
  • protein heterodimerization activity Source: ParkinsonsUK-UCL
  • transcription factor binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi199078. 2 interactors.
DIPiDIP-60705N.
STRINGi10090.ENSMUSP00000026475.

Chemistry databases

BindingDBiP35639.

Structurei

3D structure databases

ProteinModelPortaliP35639.
SMRiP35639.
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
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR004827. bZIP.
IPR016670. DNA_damage_induc_transcript_3.
[Graphical view]
PANTHERiPTHR16833. PTHR16833. 1 hit.
PIRSFiPIRSF016571. C/EBPzeta_CHOP_DDIT3. 1 hit.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]

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).Curated1

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.

Cross-referencesi

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.

3D structure databases

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

Protein-protein interaction databases

BioGridi199078. 2 interactors.
DIPiDIP-60705N.
STRINGi10090.ENSMUSP00000026475.

Chemistry databases

BindingDBiP35639.
ChEMBLiCHEMBL2146304.

PTM databases

iPTMnetiP35639.
PhosphoSitePlusiP35639.

Proteomic databases

MaxQBiP35639.
PaxDbiP35639.
PRIDEiP35639.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1649.
MGIiMGI:109247. Ddit3.

Phylogenomic databases

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

Miscellaneous databases

PROiP35639.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

InterProiIPR004827. bZIP.
IPR016670. DNA_damage_induc_transcript_3.
[Graphical view]
PANTHERiPTHR16833. PTHR16833. 1 hit.
PIRSFiPIRSF016571. C/EBPzeta_CHOP_DDIT3. 1 hit.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDDIT3_MOUSE
AccessioniPrimary (citable) accession number: P35639
Secondary accession number(s): Q91YW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 139 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.