DDIT3_CRIGR
ID DDIT3_CRIGR Reviewed; 168 AA.
AC P14607;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 25-MAY-2022, entry version 107.
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 Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=2573827; DOI=10.1128/mcb.9.10.4196-4203.1989;
RA Fornace A.J. Jr., Nebert D.W., Hollander M.C., Luethy J.D.,
RA Papathanasiou M., Fargnoli J., Holbrook N.J.;
RT "Mammalian genes coordinately regulated by growth arrest signals and DNA-
RT damaging agents.";
RL Mol. Cell. Biol. 9:4196-4203(1989).
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 (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}.
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DR EMBL; M29238; AAA36982.1; -; mRNA.
DR AlphaFoldDB; P14607; -.
DR SMR; P14607; -.
DR eggNOG; KOG3119; Eukaryota.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0001955; P:blood vessel maturation; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR004827; bZIP.
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 PROSITE; PS50217; BZIP; 1.
PE 2: Evidence at transcript level;
KW Activator; Apoptosis; Cell cycle; Cytoplasm; DNA-binding; Growth arrest;
KW Nucleus; Phosphoprotein; Repressor; Stress response; Transcription;
KW Transcription regulation; Ubl conjugation; Unfolded protein response;
KW Wnt signaling pathway.
FT CHAIN 1..168
FT /note="DNA damage-inducible transcript 3 protein"
FT /id="PRO_0000076641"
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 30..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..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 32..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..157
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; 18831 MW; 5FD5A2A6C5228771 CRC64;
MAAESLPFTL ETVSSWELEA WYEDLQEVLS SDENGGPYSS SLGNEEGESK TFTTLDPASL
AWLTEEPGPA EVTSSSQSPR SPDSSQSCMA QEEEEDQGRT RKRKQSGQCP ARGTGKQRMK
EKEQENERKV AQLAEENERL KQEIERLTRE VEATRPGSDR PHVNLQQV
