DDIT3_RAT
ID DDIT3_RAT Reviewed; 168 AA.
AC Q62857;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 126.
DE RecName: Full=DNA damage-inducible transcript 3 protein;
DE Short=DDIT-3;
DE AltName: Full=C/EBP zeta;
DE AltName: Full=C/EBP-homologous protein;
DE Short=CHOP;
DE AltName: Full=C/EBP-homologous protein 10;
DE Short=CHOP-10;
DE AltName: Full=CCAAT/enhancer-binding protein homologous protein;
DE AltName: Full=Growth arrest and DNA-damage-inducible protein GADD153;
GN Name=Ddit3; Synonyms=Chop, Chop10, Gadd153;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Jin K.L., Chen J., Simon R.P., Graham S.H.;
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Multifunctional transcription factor in ER stress response.
CC Plays an essential role in the response to a wide variety of cell
CC stresses and induces cell cycle arrest and apoptosis in response to ER
CC stress. Plays a dual role both as an inhibitor of CCAAT/enhancer-
CC binding protein (C/EBP) function and as an activator of other genes.
CC Acts as a dominant-negative regulator of C/EBP-induced transcription:
CC dimerizes with members of the C/EBP family, impairs their association
CC with C/EBP binding sites in the promoter regions, and inhibits the
CC expression of C/EBP regulated genes. Positively regulates the
CC transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34,
CC BBC3/PUMA, BCL2L11/BIM and ERO1L. Negatively regulates; expression of
CC BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine
CC synthetase (ASNS), CEBPA-dependent transcriptional activation of
CC hepcidin (HAMP) and CEBPB-mediated expression of peroxisome
CC proliferator-activated receptor gamma (PPARG). Inhibits the canonical
CC Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-
CC binding properties and repressing its transcriptional activity. Plays a
CC regulatory role in the inflammatory response through the induction of
CC caspase-11 (CASP4/CASP11) which induces the activation of caspase-1
CC (CASP1) and both these caspases increase the activation of pro-IL1B to
CC mature IL1B which is involved in the inflammatory response. Acts as a
CC major regulator of postnatal neovascularization through regulation of
CC endothelial nitric oxide synthase (NOS3)-related signaling (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer (By similarity). Interacts with TCF7L2/TCF4,
CC EP300/P300, HDAC1, HDAC5 and HDAC6. Interacts with TRIB3 which blocks
CC its association with EP300/P300. Interacts with FOXO3, CEBPB and ATF4
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00978}. Note=Present in the cytoplasm
CC under non-stressed conditions and ER stress leads to its nuclear
CC accumulation. {ECO:0000250}.
CC -!- DOMAIN: The N-terminal region is necessary for its proteasomal
CC degradation, transcriptional activity and interaction with EP300/P300.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at serine residues by MAPK14 enhances its
CC transcriptional activation activity while phosphorylation at serine
CC residues by CK2 inhibits its transcriptional activation activity.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U36994; AAA87944.1; -; mRNA.
DR AlphaFoldDB; Q62857; -.
DR SMR; Q62857; -.
DR ComplexPortal; CPX-60; bZIP transcription factor complex, Cebpa-Ddit3.
DR ComplexPortal; CPX-62; bZIP transcription factor complex, Cebpb-Ddit3.
DR IntAct; Q62857; 3.
DR STRING; 10116.ENSRNOP00000008941; -.
DR ChEMBL; CHEMBL3797018; -.
DR PhosphoSitePlus; Q62857; -.
DR PaxDb; Q62857; -.
DR UCSC; RGD:62391; rat.
DR RGD; 62391; Ddit3.
DR eggNOG; KOG3119; Eukaryota.
DR InParanoid; Q62857; -.
DR PhylomeDB; Q62857; -.
DR PRO; PR:Q62857; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:1990622; C:CHOP-ATF3 complex; ISO:RGD.
DR GO; GO:1990617; C:CHOP-ATF4 complex; ISO:RGD.
DR GO; GO:0036488; C:CHOP-C/EBP complex; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005770; C:late endosome; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032993; C:protein-DNA complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0008140; F:cAMP response element binding protein binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0043522; F:leucine zipper domain binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0009948; P:anterior/posterior axis specification; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0060840; P:artery development; ISO:RGD.
DR GO; GO:0001955; P:blood vessel maturation; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045454; P:cell redox homeostasis; ISO:RGD.
DR GO; GO:0071287; P:cellular response to manganese ion; IEP:ParkinsonsUK-UCL.
DR GO; GO:0048568; P:embryonic organ development; IEP:RGD.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0006983; P:ER overload response; IMP:RGD.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:1990442; P:intrinsic apoptotic signaling pathway in response to nitrosative stress; ISO:RGD.
DR GO; GO:0001554; P:luteolysis; IEP:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0032792; P:negative regulation of CREB transcription factor activity; IDA:RGD.
DR GO; GO:2000016; P:negative regulation of determination of dorsal identity; ISO:RGD.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0032713; P:negative regulation of interleukin-4 production; ISO:RGD.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0034263; P:positive regulation of autophagy in response to ER overload; IMP:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IEP:RGD.
DR GO; GO:0036119; P:response to platelet-derived growth factor; ISO:RGD.
DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0006986; P:response to unfolded protein; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; ISO:RGD.
DR GO; GO:1990874; P:vascular associated smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR016670; DNA_damage_induc_transcript_3.
DR PANTHER; PTHR16833; PTHR16833; 1.
DR PIRSF; PIRSF016571; C/EBPzeta_CHOP_DDIT3; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 2: Evidence at transcript level;
KW Activator; Apoptosis; Cell cycle; Cytoplasm; DNA-binding; Growth arrest;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Stress response;
KW Transcription; Transcription regulation; Ubl conjugation;
KW Unfolded protein response; Wnt signaling pathway.
FT CHAIN 1..168
FT /note="DNA damage-inducible transcript 3 protein"
FT /id="PRO_0000076644"
FT DOMAIN 98..161
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 10..26
FT /note="N-terminal"
FT /evidence="ECO:0000250"
FT REGION 10..18
FT /note="Interaction with TRIB3"
FT /evidence="ECO:0000250"
FT REGION 34..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..129
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 133..147
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 34..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..130
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 14
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT MOD_RES 15
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT MOD_RES 30
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT MOD_RES 31
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT MOD_RES 78
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT MOD_RES 81
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P35639"
SQ SEQUENCE 168 AA; 19013 MW; 251716CD712BA6E1 CRC64;
MAAESLPFAF ETVSSWELEA WYEDLQEVLS SDEIGGTYIS SPGNEEEESK TFTTLDPASL
AWLTEEPGPA EVTSTSQSPR SPDSSQSSMA QEEEEEDQGR TRKRKQSGQC AARAGKQRMK
EKEQENERKV AQLAEENERL KLEIERLTRE VETTRRALID RMVSLHQA
