DDIT3_HUMAN
ID DDIT3_HUMAN Reviewed; 169 AA.
AC P35638; F8VS99;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 210.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1339368; DOI=10.1016/0378-1119(92)90523-r;
RA Park J.S., Luethy J.D., Wang M.G., Fargnoli J., Fornace A.J. Jr.,
RA McBride O.W., Holbrook N.J.;
RT "Isolation, characterization and chromosomal localization of the human
RT GADD153 gene.";
RL Gene 116:259-267(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8510758; DOI=10.1038/363640a0;
RA Crozat A., Aman P., Mandahl N., Ron D.;
RT "Fusion of CHOP to a novel RNA-binding protein in human myxoid
RT liposarcoma.";
RL Nature 363:640-644(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN MXLIPO, AND
RP CHROMOSOMAL TRANSLOCATION WITH FUS.
RX PubMed=7503811; DOI=10.1038/ng0693-175;
RA Rabbitts T.H., Forster A., Larson R., Nathan P.;
RT "Fusion of the dominant negative transcription regulator CHOP with a novel
RT gene FUS by translocation t(12;16) in malignant liposarcoma.";
RL Nat. Genet. 4:175-180(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Li X., Xie Y., Mao Y.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP REVIEW.
RX PubMed=14685163; DOI=10.1038/sj.cdd.4401373;
RA Oyadomari S., Mori M.;
RT "Roles of CHOP/GADD153 in endoplasmic reticulum stress.";
RL Cell Death Differ. 11:381-389(2004).
RN [9]
RP FUNCTION.
RX PubMed=15322075; DOI=10.1074/jbc.m406933200;
RA Yamaguchi H., Wang H.G.;
RT "CHOP is involved in endoplasmic reticulum stress-induced apoptosis by
RT enhancing DR5 expression in human carcinoma cells.";
RL J. Biol. Chem. 279:45495-45502(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH TRIB3.
RX PubMed=15775988; DOI=10.1038/sj.emboj.7600596;
RA Ohoka N., Yoshii S., Hattori T., Onozaki K., Hayashi H.;
RT "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway
RT and is involved in cell death.";
RL EMBO J. 24:1243-1255(2005).
RN [11]
RP FUNCTION, AND INTERACTION WITH TCF7L2.
RX PubMed=16434966; DOI=10.1038/sj.onc.1209380;
RA Horndasch M., Lienkamp S., Springer E., Schmitt A., Pavenstaedt H.,
RA Walz G., Gloy J.;
RT "The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF
RT signals.";
RL Oncogene 25:3397-3407(2006).
RN [12]
RP N-TERMINAL REGION, SUBCELLULAR LOCATION, INTERACTION WITH TRIB3; EP300;
RP HDAC1; HDAC5 AND HDAC6, UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=17872950; DOI=10.1074/jbc.m703735200;
RA Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H.;
RT "Critical and functional regulation of CHOP (C/EBP homologous protein)
RT through the N-terminal portion.";
RL J. Biol. Chem. 282:35687-35694(2007).
RN [13]
RP FUNCTION.
RX PubMed=17709599; DOI=10.1165/rcmb.2007-0197oc;
RA Vij N., Amoako M.O., Mazur S., Zeitlin P.L.;
RT "CHOP transcription factor mediates IL-8 signaling in cystic fibrosis
RT bronchial epithelial cells.";
RL Am. J. Respir. Cell Mol. Biol. 38:176-184(2008).
RN [14]
RP FUNCTION, AND INTERACTION WITH ATF4.
RX PubMed=18940792; DOI=10.1074/jbc.m806874200;
RA Su N., Kilberg M.S.;
RT "C/EBP homology protein (CHOP) interacts with activating transcription
RT factor 4 (ATF4) and negatively regulates the stress-dependent induction of
RT the asparagine synthetase gene.";
RL J. Biol. Chem. 283:35106-35117(2008).
RN [15]
RP INDUCTION.
RX PubMed=19855386; DOI=10.1038/ncb1996;
RA Woo C.W., Cui D., Arellano J., Dorweiler B., Harding H., Fitzgerald K.A.,
RA Ron D., Tabas I.;
RT "Adaptive suppression of the ATF4-CHOP branch of the unfolded protein
RT response by toll-like receptor signalling.";
RL Nat. Cell Biol. 11:1473-1480(2009).
RN [16]
RP FUNCTION.
RX PubMed=19672300; DOI=10.1371/journal.pone.0006618;
RA Oliveira S.J., Pinto J.P., Picarote G., Costa V.M., Carvalho F., Rangel M.,
RA de Sousa M., de Almeida S.F.;
RT "ER stress-inducible factor CHOP affects the expression of hepcidin by
RT modulating C/EBPalpha activity.";
RL PLoS ONE 4:E6618-E6618(2009).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CEBPB, AND INDUCTION.
RX PubMed=20829347; DOI=10.1074/jbc.m110.136259;
RA Park S.H., Choi H.J., Yang H., Do K.H., Kim J., Lee D.W., Moon Y.;
RT "Endoplasmic reticulum stress-activated C/EBP homologous protein enhances
RT nuclear factor-kappaB signals via repression of peroxisome proliferator-
RT activated receptor gamma.";
RL J. Biol. Chem. 285:35330-35339(2010).
RN [18]
RP FUNCTION.
RX PubMed=20876114; DOI=10.1073/pnas.1011736107;
RA Goodall J.C., Wu C., Zhang Y., McNeill L., Ellis L., Saudek V.,
RA Gaston J.S.;
RT "Endoplasmic reticulum stress-induced transcription factor, CHOP, is
RT crucial for dendritic cell IL-23 expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:17698-17703(2010).
RN [19]
RP REVIEW.
RX PubMed=22210905; DOI=10.1093/jb/mvr143;
RA Nishitoh H.;
RT "CHOP is a multifunctional transcription factor in the ER stress
RT response.";
RL J. Biochem. 151:217-219(2012).
RN [20]
RP FUNCTION, INTERACTION WITH FOXO3, AND SUBCELLULAR LOCATION.
RX PubMed=22761832; DOI=10.1371/journal.pone.0039586;
RA Ghosh A.P., Klocke B.J., Ballestas M.E., Roth K.A.;
RT "CHOP potentially co-operates with FOXO3a in neuronal cells to regulate
RT PUMA and BIM expression in response to ER stress.";
RL PLoS ONE 7:E39586-E39586(2012).
RN [21]
RP SUBCELLULAR LOCATION, ALTERNATIVE INITIATION (ISOFORM ALTDDIT3), AND
RP SUBUNIT.
RX PubMed=29083303; DOI=10.7554/elife.27860;
RA Samandi S., Roy A.V., Delcourt V., Lucier J.F., Gagnon J., Beaudoin M.C.,
RA Vanderperre B., Breton M.A., Motard J., Jacques J.F., Brunelle M.,
RA Gagnon-Arsenault I., Fournier I., Ouangraoua A., Hunting D.J., Cohen A.A.,
RA Landry C.R., Scott M.S., Roucou X.;
RT "Deep transcriptome annotation enables the discovery and functional
RT characterization of cryptic small proteins.";
RL Elife 6:0-0(2017).
RN [22]
RP SUBCELLULAR LOCATION, AND INDUCTION BY ER STRESS.
RX PubMed=33384352; DOI=10.1126/science.abb6896;
RA You K., Wang L., Chou C.H., Liu K., Nakata T., Jaiswal A., Yao J.,
RA Lefkovith A., Omar A., Perrigoue J.G., Towne J.E., Regev A., Graham D.B.,
RA Xavier R.J.;
RT "QRICH1 dictates the outcome of ER stress through transcriptional control
RT of proteostasis.";
RL Science 371:0-0(2021).
RN [23]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-115.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Multifunctional transcription factor in endoplasmic reticulum
CC (ER) stress response (PubMed:15322075, PubMed:15775988,
CC PubMed:19672300). Plays an essential role in the response to a wide
CC variety of cell stresses and induces cell cycle arrest and apoptosis in
CC response to ER stress (PubMed:15322075, PubMed:15775988). Plays a dual
CC role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP)
CC function and as an activator of other genes (By similarity). Acts as a
CC dominant-negative regulator of C/EBP-induced transcription: dimerizes
CC with members of the C/EBP family, impairs their association with C/EBP
CC binding sites in the promoter regions, and inhibits the expression of
CC C/EBP regulated genes (By similarity). Positively regulates the
CC transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34,
CC BBC3/PUMA, BCL2L11/BIM and ERO1L (PubMed:15775988, PubMed:17709599,
CC PubMed:22761832, PubMed:20876114). 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) (PubMed:18940792,
CC PubMed:19672300, PubMed:20829347). Together with ATF4, mediates ER-
CC mediated cell death by promoting expression of genes involved in
CC cellular amino acid metabolic processes, mRNA translation and the
CC unfolded protein response (UPR) in response to ER stress (By
CC similarity). Inhibits the canonical Wnt signaling pathway by binding to
CC TCF7L2/TCF4, impairing its DNA-binding properties and repressing its
CC transcriptional activity (PubMed:16434966). Plays a regulatory role in
CC the inflammatory response through the induction of caspase-11
CC (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and
CC both these caspases increase the activation of pro-IL1B to mature IL1B
CC which is involved in the inflammatory response (By similarity). Acts as
CC a major regulator of postnatal neovascularization through regulation of
CC endothelial nitric oxide synthase (NOS3)-related signaling (By
CC similarity). {ECO:0000250|UniProtKB:P35639,
CC ECO:0000269|PubMed:15322075, ECO:0000269|PubMed:15775988,
CC ECO:0000269|PubMed:16434966, ECO:0000269|PubMed:17709599,
CC ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:19672300,
CC ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:20876114,
CC ECO:0000269|PubMed:22761832}.
CC -!- SUBUNIT: Heterodimer (PubMed:29083303). Interacts with TCF7L2/TCF4,
CC EP300/P300, HDAC1, HDAC5 and HDAC6 (PubMed:17872950, PubMed:16434966).
CC Interacts with TRIB3 which blocks its association with EP300/P300
CC (PubMed:15775988, PubMed:17872950). Interacts with FOXO3, CEBPB and
CC ATF4 (PubMed:18940792, PubMed:20829347, PubMed:22761832).
CC {ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16434966,
CC ECO:0000269|PubMed:17872950, ECO:0000269|PubMed:18940792,
CC ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:22761832,
CC ECO:0000269|PubMed:29083303}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with isoform AltDDIT3 of DDIT3.
CC {ECO:0000269|PubMed:29083303}.
CC -!- INTERACTION:
CC P35638; P15336: ATF2; NbExp=2; IntAct=EBI-742651, EBI-1170906;
CC P35638; P18847: ATF3; NbExp=23; IntAct=EBI-742651, EBI-712767;
CC P35638; P18848: ATF4; NbExp=5; IntAct=EBI-742651, EBI-492498;
CC P35638; O14867: BACH1; NbExp=2; IntAct=EBI-742651, EBI-1263541;
CC P35638; Q16520: BATF; NbExp=8; IntAct=EBI-742651, EBI-749503;
CC P35638; Q8N1L9: BATF2; NbExp=2; IntAct=EBI-742651, EBI-742695;
CC P35638; Q9NR55: BATF3; NbExp=8; IntAct=EBI-742651, EBI-10312707;
CC P35638; P49715: CEBPA; NbExp=4; IntAct=EBI-742651, EBI-1172054;
CC P35638; P17676: CEBPB; NbExp=2; IntAct=EBI-742651, EBI-969696;
CC P35638; P49716: CEBPD; NbExp=2; IntAct=EBI-742651, EBI-7962058;
CC P35638; Q15744: CEBPE; NbExp=3; IntAct=EBI-742651, EBI-3907048;
CC P35638; P53567: CEBPG; NbExp=6; IntAct=EBI-742651, EBI-740209;
CC P35638; Q9BSW2: CRACR2A; NbExp=3; IntAct=EBI-742651, EBI-739773;
CC P35638; O43889: CREB3; NbExp=2; IntAct=EBI-742651, EBI-625002;
CC P35638; O60519: CREBL2; NbExp=3; IntAct=EBI-742651, EBI-2872455;
CC P35638; Q10586: DBP; NbExp=4; IntAct=EBI-742651, EBI-3908088;
CC P35638; P35638: DDIT3; NbExp=2; IntAct=EBI-742651, EBI-742651;
CC P35638; Q7Z589-5: EMSY; NbExp=3; IntAct=EBI-742651, EBI-11989522;
CC P35638; P01100: FOS; NbExp=8; IntAct=EBI-742651, EBI-852851;
CC P35638; P15408: FOSL2; NbExp=6; IntAct=EBI-742651, EBI-3893419;
CC P35638; Q13283: G3BP1; NbExp=2; IntAct=EBI-742651, EBI-1047359;
CC P35638; P14136: GFAP; NbExp=3; IntAct=EBI-742651, EBI-744302;
CC P35638; Q16534: HLF; NbExp=3; IntAct=EBI-742651, EBI-2798854;
CC P35638; Q9BPX1: HSD17B14; NbExp=6; IntAct=EBI-742651, EBI-742664;
CC P35638; Q8WYK2: JDP2; NbExp=3; IntAct=EBI-742651, EBI-1248415;
CC P35638; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-742651, EBI-1055254;
CC P35638; P17275: JUNB; NbExp=2; IntAct=EBI-742651, EBI-748062;
CC P35638; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-742651, EBI-739832;
CC P35638; Q9BTE3-2: MCMBP; NbExp=3; IntAct=EBI-742651, EBI-9384556;
CC P35638; Q16236: NFE2L2; NbExp=5; IntAct=EBI-742651, EBI-2007911;
CC P35638; Q16649: NFIL3; NbExp=2; IntAct=EBI-742651, EBI-3951858;
CC P35638; O43508: TNFSF12; NbExp=3; IntAct=EBI-742651, EBI-6932080;
CC P35638; Q99757: TXN2; NbExp=3; IntAct=EBI-742651, EBI-2932492;
CC P35638; Q86VQ3: TXNDC2; NbExp=3; IntAct=EBI-742651, EBI-1220595;
CC P35638; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-742651, EBI-2559305;
CC P35638-2; Q9Y2J4-4: AMOTL2; NbExp=3; IntAct=EBI-10173632, EBI-10187270;
CC P35638-2; Q8N5M1: ATPAF2; NbExp=3; IntAct=EBI-10173632, EBI-1166928;
CC P35638-2; Q9NR55: BATF3; NbExp=3; IntAct=EBI-10173632, EBI-10312707;
CC P35638-2; Q494R4: CCDC153; NbExp=3; IntAct=EBI-10173632, EBI-10241443;
CC P35638-2; P53567: CEBPG; NbExp=3; IntAct=EBI-10173632, EBI-740209;
CC P35638-2; Q7Z589: EMSY; NbExp=3; IntAct=EBI-10173632, EBI-6598631;
CC P35638-2; P15408: FOSL2; NbExp=3; IntAct=EBI-10173632, EBI-3893419;
CC P35638-2; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-10173632, EBI-742664;
CC P35638-2; P25791: LMO2; NbExp=3; IntAct=EBI-10173632, EBI-739696;
CC P35638-2; O75971: SNAPC5; NbExp=3; IntAct=EBI-10173632, EBI-749483;
CC P35638-2; Q4ACW9: TWEAK; NbExp=3; IntAct=EBI-10173632, EBI-10241785;
CC P35638-2; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-10173632, EBI-2559305;
CC P35638-2; P24278: ZBTB25; NbExp=3; IntAct=EBI-10173632, EBI-739899;
CC P35638-2; Q6PJT7: ZC3H14; NbExp=3; IntAct=EBI-10173632, EBI-740660;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29083303}. Nucleus
CC {ECO:0000269|PubMed:29083303, ECO:0000269|PubMed:33384352}.
CC Note=Present in the cytoplasm under non-stressed conditions and ER
CC stress leads to its nuclear accumulation.
CC {ECO:0000269|PubMed:29083303}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=1;
CC IsoId=P35638-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35638-2; Sequence=VSP_047277;
CC Name=AltDDIT3;
CC IsoId=P0DPQ6-1; Sequence=External;
CC -!- INDUCTION: Up-regulated by oxidative stress, amino-acid deprivation,
CC hypoxia and endoplasmic reticulum stress (PubMed:33384352). During ER
CC stress, induced by a EIF2AK3/ATF4 pathway and/or ERN1/ATF6 pathway.
CC Expression is suppressed by TLR-TRIF signaling pathway during prolonged
CC ER stress. {ECO:0000269|PubMed:19855386, ECO:0000269|PubMed:20829347,
CC ECO:0000269|PubMed:33384352}.
CC -!- DOMAIN: The N-terminal region is necessary for its proteasomal
CC degradation, transcriptional activity and interaction with EP300/P300.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:17872950}.
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 -!- DISEASE: Myxoid liposarcoma (MXLIPO) [MIM:613488]: A soft tissue tumor
CC that tends to occur in the limbs (especially the thigh) of patients
CC ranging in age from 35 to 55 years. It is defined by the presence of a
CC hypocellular spindle cell proliferation set in a myxoid background,
CC often with mucin pooling. Lipoblasts tend to be small and often
CC monovacuolated and to cluster around vessels or at the periphery of the
CC lesion. {ECO:0000269|PubMed:7503811}. Note=The gene represented in this
CC entry may be involved in disease pathogenesis. A chromosomal aberration
CC involving DDIT3 has been found in a patient with malignant myxoid
CC liposarcoma. Translocation t(12;16)(q13;p11) with FUS (PubMed:7503811).
CC {ECO:0000269|PubMed:7503811}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB27103.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DDIT3ID80.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ddit3/";
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DR EMBL; S40706; AAB22646.1; -; mRNA.
DR EMBL; S62138; AAB27103.1; ALT_SEQ; mRNA.
DR EMBL; AY461580; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY880949; AAW56077.1; -; Genomic_DNA.
DR EMBL; AC022506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003637; AAH03637.1; -; mRNA.
DR CCDS; CCDS55838.1; -. [P35638-2]
DR CCDS; CCDS8943.1; -. [P35638-1]
DR PIR; JC1169; JC1169.
DR PIR; S33798; S33798.
DR RefSeq; NP_001181982.1; NM_001195053.1. [P35638-2]
DR RefSeq; NP_001181983.1; NM_001195054.1. [P35638-2]
DR RefSeq; NP_001181984.1; NM_001195055.1. [P35638-2]
DR RefSeq; NP_001181986.1; NM_001195057.1. [P35638-1]
DR RefSeq; NP_004074.2; NM_004083.5. [P35638-1]
DR AlphaFoldDB; P35638; -.
DR SMR; P35638; -.
DR BioGRID; 108016; 120.
DR ComplexPortal; CPX-2496; bZIP transcription factor complex, BACH1-DDIT3.
DR ComplexPortal; CPX-6415; bZIP transcription factor complex, ATF2-DDIT3.
DR ComplexPortal; CPX-6473; bZIP transcription factor complex, ATF3-DDIT3.
DR ComplexPortal; CPX-6543; bZIP transcription factor complex, ATF4-DDIT3.
DR ComplexPortal; CPX-6784; bZIP transcription factor complex, ATF7-DDIT3.
DR ComplexPortal; CPX-69; bZIP transcription factor complex, CEBPA-DDIT3.
DR ComplexPortal; CPX-70; bZIP transcription factor complex, CEBPB-DDIT3.
DR ComplexPortal; CPX-7004; bZIP transcription factor complex, BATF-DDIT3.
DR ComplexPortal; CPX-7064; bZIP transcription factor complex, BATF2-DDIT3.
DR ComplexPortal; CPX-7106; bZIP transcription factor complex, BATF3-DDIT3.
DR CORUM; P35638; -.
DR DIP; DIP-41589N; -.
DR IntAct; P35638; 70.
DR MINT; P35638; -.
DR STRING; 9606.ENSP00000448665; -.
DR ChEMBL; CHEMBL3351207; -.
DR GlyGen; P35638; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P35638; -.
DR PhosphoSitePlus; P35638; -.
DR BioMuta; DDIT3; -.
DR DMDM; 544022; -.
DR jPOST; P35638; -.
DR MassIVE; P35638; -.
DR PaxDb; P35638; -.
DR PeptideAtlas; P35638; -.
DR PRIDE; P35638; -.
DR ProteomicsDB; 28566; -.
DR ProteomicsDB; 55121; -. [P35638-1]
DR Antibodypedia; 4408; 1040 antibodies from 43 providers.
DR CPTC; P35638; 3 antibodies.
DR DNASU; 1649; -.
DR Ensembl; ENST00000346473.8; ENSP00000340671.3; ENSG00000175197.13. [P35638-1]
DR Ensembl; ENST00000547303.5; ENSP00000447188.1; ENSG00000175197.13. [P35638-1]
DR Ensembl; ENST00000551116.5; ENSP00000448665.1; ENSG00000175197.13. [P35638-2]
DR Ensembl; ENST00000552740.5; ENSP00000447803.1; ENSG00000175197.13. [P35638-2]
DR Ensembl; ENST00000623876.2; ENSP00000494844.1; ENSG00000175197.13. [P35638-1]
DR GeneID; 1649; -.
DR KEGG; hsa:1649; -.
DR MANE-Select; ENST00000346473.8; ENSP00000340671.3; NM_004083.6; NP_004074.2.
DR UCSC; uc009zps.4; human. [P35638-1]
DR CTD; 1649; -.
DR DisGeNET; 1649; -.
DR GeneCards; DDIT3; -.
DR HGNC; HGNC:2726; DDIT3.
DR HPA; ENSG00000175197; Low tissue specificity.
DR MalaCards; DDIT3; -.
DR MIM; 126337; gene.
DR MIM; 613488; phenotype.
DR neXtProt; NX_P35638; -.
DR OpenTargets; ENSG00000175197; -.
DR Orphanet; 99967; Myxoid/round cell liposarcoma.
DR PharmGKB; PA27193; -.
DR VEuPathDB; HostDB:ENSG00000175197; -.
DR eggNOG; KOG3119; Eukaryota.
DR GeneTree; ENSGT00390000006305; -.
DR HOGENOM; CLU_135108_0_0_1; -.
DR InParanoid; P35638; -.
DR OMA; QCPARAG; -.
DR OrthoDB; 1338770at2759; -.
DR PhylomeDB; P35638; -.
DR TreeFam; TF105006; -.
DR PathwayCommons; P35638; -.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-381183; ATF6 (ATF6-alpha) activates chaperone genes.
DR Reactome; R-HSA-9614657; FOXO-mediated transcription of cell death genes.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; P35638; -.
DR SIGNOR; P35638; -.
DR BioGRID-ORCS; 1649; 31 hits in 1097 CRISPR screens.
DR ChiTaRS; DDIT3; human.
DR GeneWiki; DNA_damage-inducible_transcript_3; -.
DR GenomeRNAi; 1649; -.
DR Pharos; P35638; Tchem.
DR PRO; PR:P35638; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P35638; protein.
DR Bgee; ENSG00000175197; Expressed in adenohypophysis and 94 other tissues.
DR ExpressionAtlas; P35638; baseline and differential.
DR Genevisible; P35638; HS.
DR GO; GO:1990622; C:CHOP-ATF3 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990617; C:CHOP-ATF4 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0036488; C:CHOP-C/EBP complex; IPI:ComplexPortal.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005770; C:late endosome; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032993; C:protein-DNA complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; NAS:ParkinsonsUK-UCL.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IGI:ParkinsonsUK-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043522; F:leucine zipper domain binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISS:ARUK-UCL.
DR GO; GO:0009948; P:anterior/posterior axis specification; ISS:BHF-UCL.
DR GO; GO:0060840; P:artery development; IEA:Ensembl.
DR GO; GO:0036500; P:ATF6-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:0001955; P:blood vessel maturation; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; TAS:ProtInc.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0006983; P:ER overload response; IBA:GO_Central.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0140467; P:integrated stress response signaling; IC:ComplexPortal.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:1990442; P:intrinsic apoptotic signaling pathway in response to nitrosative stress; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:BHF-UCL.
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:ParkinsonsUK-UCL.
DR GO; GO:2000016; P:negative regulation of determination of dorsal identity; IDA:BHF-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:ARUK-UCL.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:ARUK-UCL.
DR GO; GO:0032713; P:negative regulation of interleukin-4 production; IMP:ARUK-UCL.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:ARUK-UCL.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IDA:ParkinsonsUK-UCL.
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; IDA:UniProtKB.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:CAFA.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IC:ParkinsonsUK-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
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:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0043618; P:regulation of transcription from RNA polymerase II promoter in response to stress; TAS:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0036119; P:response to platelet-derived growth factor; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; IDA:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1990874; P:vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR DisProt; DP00624; -.
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 1: Evidence at protein level;
KW Activator; Alternative initiation; Alternative splicing; Apoptosis;
KW Cell cycle; Chromosomal rearrangement; Cytoplasm; DNA-binding;
KW Growth arrest; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Repressor; Stress response; Transcription; Transcription regulation;
KW Ubl conjugation; Unfolded protein response; Wnt signaling pathway.
FT CHAIN 1..169
FT /note="DNA damage-inducible transcript 3 protein"
FT /id="PRO_0000076642"
FT DOMAIN 99..162
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 10..26
FT /note="N-terminal"
FT REGION 10..18
FT /note="Interaction with TRIB3"
FT REGION 32..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..130
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 134..148
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 70..89
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..139
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 79
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT MOD_RES 82
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P35639"
FT VAR_SEQ 1
FT /note="M -> MELVPATPHYPADVLFQTDPTAEM (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047277"
FT VARIANT 115
FT /note="A -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036000"
FT CONFLICT 10..14
FT /note="FGTLS -> SDTV (in Ref. 1; AAB22646)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 169 AA; 19175 MW; 31905293FB1FBBE2 CRC64;
MAAESLPFSF GTLSSWELEA WYEDLQEVLS SDENGGTYVS PPGNEEEESK IFTTLDPASL
AWLTEEEPEP AEVTSTSQSP HSPDSSQSSL AQEEEEEDQG RTRKRKQSGH SPARAGKQRM
KEKEQENERK VAQLAEENER LKQEIERLTR EVEATRRALI DRMVNLHQA
