Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P35639 (DDIT3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ddit3
Synonyms:Chop, Chop10, Gadd153
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length168 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling. Ref.1 Ref.4 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15

Subunit structure

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. Ref.14

Subcellular location

Cytoplasm. Nucleus. Note: Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation. Ref.1 Ref.14

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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Domain

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

Post-translational modification

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.

Sequence similarities

Belongs to the bZIP family.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Growth arrest
Stress response
Transcription
Transcription regulation
Unfolded protein response
Wnt signaling pathway
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionActivator
Repressor
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER overload response

Inferred from mutant phenotype PubMed 11854325. Source: MGI

Wnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from mutant phenotype Ref.15. Source: UniProtKB

blood vessel maturation

Inferred from mutant phenotype Ref.15. Source: UniProtKB

cell cycle arrest

Inferred from electronic annotation. Source: UniProtKB-KW

cell redox homeostasis

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum unfolded protein response

Inferred from mutant phenotype Ref.7. Source: MGI

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from mutant phenotype Ref.13. Source: UniProtKB

mRNA transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 16434966. Source: BHF-UCL

negative regulation of determination of dorsal identity

Inferred from direct assay PubMed 16434966. Source: BHF-UCL

negative regulation of myoblast differentiation

Inferred from mutant phenotype Ref.14. Source: UniProtKB

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.14. Source: UniProtKB

positive regulation of interleukin-8 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron apoptotic process

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.13. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of transcription involved in anterior/posterior axis specification

Inferred from direct assay PubMed 16434966. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.8Ref.10. Source: UniProtKB

release of sequestered calcium ion into cytosol

Inferred from mutant phenotype Ref.10. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from direct assay Ref.10Ref.13. Source: UniProtKB

response to starvation

Inferred from direct assay Ref.14. Source: UniProtKB

   Cellular_componentlate endosome

Inferred from direct assay PubMed 23028046. Source: MGI

nucleus

Inferred from direct assay Ref.14. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.7. Source: MGI

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype Ref.7. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 168168DNA damage-inducible transcript 3 protein
PRO_0000076643

Regions

Domain98 – 16164bZIP
Region10 – 2617N-terminal By similarity
Region10 – 189Interaction with TRIB3 By similarity
Region100 – 12930Basic motif By similarity
Region133 – 14715Leucine-zipper By similarity
Compositional bias92 – 976Poly-Glu

Amino acid modifications

Modified residue141Phosphoserine; by CK2 Ref.5
Modified residue151Phosphoserine; by CK2 Ref.5
Modified residue301Phosphoserine; by CK2 Ref.5
Modified residue311Phosphoserine; by CK2 Ref.5
Modified residue781Phosphoserine; by MAPK14 Ref.3
Modified residue811Phosphoserine; by MAPK14 Ref.3

Experimental info

Mutagenesis141S → A: Loss of phosphorylation. Ref.5
Mutagenesis151S → A: Loss of phosphorylation. Ref.5
Mutagenesis301S → A: Loss of phosphorylation. Ref.5
Mutagenesis311S → A: Loss of phosphorylation. Ref.5
Sequence conflict341I → N in AAH13718. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P35639 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: CA423B79512F33AB

FASTA16819,189
        10         20         30         40         50         60 
MAAESLPFTL ETVSSWELEA WYEDLQEVLS SDEIGGTYIS SPGNEEEESK TFTTLDPASL 

        70         80         90        100        110        120 
AWLTEEPGPT EVTRTSQSPR SPDSSQSSMA QEEEEEEQGR TRKRKQSGQC PARPGKQRMK 

       130        140        150        160 
EKEQENERKV AQLAEENERL KQEIERLTRE VETTRRALID RMVSLHQA 

« Hide

References

« Hide 'large scale' references
[1]"CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription."
Ron D., Habener J.F.
Genes Dev. 6:439-453(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
Strain: Swiss.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II.
Tissue: Mammary tumor.
[3]"Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase."
Wang X.Z., Ron D.
Science 272:1347-1349(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-78 AND SER-81.
[4]"C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform."
Hattori T., Ohoka N., Hayashi H., Onozaki K.
FEBS Lett. 541:33-39(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation."
Ubeda M., Habener J.F.
J. Biol. Chem. 278:40514-40520(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-14; SER-15; SER-30 AND SER-31, MUTAGENESIS OF SER-14; SER-15; SER-30 AND SER-31.
[6]"CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation."
Pereira R.C., Delany A.M., Canalis E.
Endocrinology 145:1952-1960(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum."
Marciniak S.J., Yun C.Y., Oyadomari S., Novoa I., Zhang Y., Jungreis R., Nagata K., Harding H.P., Ron D.
Genes Dev. 18:3066-3077(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death."
Ohoka N., Yoshii S., Hattori T., Onozaki K., Hayashi H.
EMBO J. 24:1243-1255(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation."
Endo M., Mori M., Akira S., Gotoh T.
J. Immunol. 176:6245-6253(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[10]"Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis."
Li G., Mongillo M., Chin K.T., Harding H., Ron D., Marks A.R., Tabas I.
J. Cell Biol. 186:783-792(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[11]"Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling."
Woo C.W., Cui D., Arellano J., Dorweiler B., Harding H., Fitzgerald K.A., Ron D., Tabas I.
Nat. Cell Biol. 11:1473-1480(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[12]"Molecular mechanisms of the LPS-induced non-apoptotic ER stress-CHOP pathway."
Nakayama Y., Endo M., Tsukano H., Mori M., Oike Y., Gotoh T.
J. Biochem. 147:471-483(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[13]"Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA."
Galehdar Z., Swan P., Fuerth B., Callaghan S.M., Park D.S., Cregan S.P.
J. Neurosci. 30:16938-16948(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[14]"Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation."
Alter J., Bengal E.
PLoS ONE 6:E29498-E29498(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH HDAC1.
[15]"C/EBP homologous protein-10 (CHOP-10) limits postnatal neovascularization through control of endothelial nitric oxide synthase gene expression."
Loinard C., Zouggari Y., Rueda P., Ramkhelawon B., Cochain C., Vilar J., Recalde A., Richart A., Charue D., Duriez M., Mori M., Arenzana-Seisdedos F., Levy B.I., Heymes C., Silvestre J.S.
Circulation 125:1014-1026(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67083 mRNA. Translation: CAA47465.1.
BC013718 mRNA. Translation: AAH13718.1.
PIRS26148.
RefSeqNP_031863.3. NM_007837.3.
XP_006513260.1. XM_006513197.1.
XP_006513261.1. XM_006513198.1.
XP_006513262.1. XM_006513199.1.
UniGeneMm.110220.

3D structure databases

ProteinModelPortalP35639.
SMRP35639. Positions 115-160.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199078. 2 interactions.

Chemistry

BindingDBP35639.
ChEMBLCHEMBL2146304.

PTM databases

PhosphoSiteP35639.

Proteomic databases

PRIDEP35639.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026475; ENSMUSP00000026475; ENSMUSG00000025408.
GeneID13198.
KEGGmmu:13198.
UCSCuc007hiy.2. mouse.

Organism-specific databases

CTD1649.
MGIMGI:109247. Ddit3.

Phylogenomic databases

eggNOGNOG279524.
GeneTreeENSGT00390000006305.
HOGENOMHOG000089934.
HOVERGENHBG051328.
InParanoidP35639.
KOK04452.
OMADRMVNLH.
OrthoDBEOG7QC7Z1.
PhylomeDBP35639.
TreeFamTF105006.

Gene expression databases

ArrayExpressP35639.
BgeeP35639.
CleanExMM_DDIT3.
GenevestigatorP35639.

Family and domain databases

InterProIPR004827. bZIP.
IPR016670. DNA_damage_induc_transcript_3.
[Graphical view]
PANTHERPTHR16833. PTHR16833. 1 hit.
PIRSFPIRSF016571. C/EBPzeta_CHOP_DDIT3. 1 hit.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio283336.
PROP35639.
SOURCESearch...

Entry information

Entry nameDDIT3_MOUSE
AccessionPrimary (citable) accession number: P35639
Secondary accession number(s): Q91YW9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot