DDIT4_HUMAN
ID DDIT4_HUMAN Reviewed; 232 AA.
AC Q9NX09; Q9H0S3;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=DNA damage-inducible transcript 4 protein;
DE AltName: Full=HIF-1 responsive protein RTP801;
DE AltName: Full=Protein regulated in development and DNA damage response 1;
DE Short=REDD-1;
GN Name=DDIT4; Synonyms=REDD1, RTP801;
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], TISSUE SPECIFICITY, INDUCTION BY DNA DAMAGE,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Fetal brain;
RX PubMed=12453409; DOI=10.1016/s1097-2765(02)00706-2;
RA Ellisen L.W., Ramsayer K.D., Johannessen C.M., Yang A., Beppu H., Minda K.,
RA Oliner J.D., McKeon F., Haber D.A.;
RT "REDD1, a developmentally regulated transcriptional target of p63 and p53,
RT links p63 to regulation of reactive oxygen species.";
RL Mol. Cell 10:995-1005(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11884613; DOI=10.1128/mcb.22.7.2283-2293.2002;
RA Shoshani T., Faerman A., Mett I., Zelin E., Tenne T., Gorodin S.,
RA Moshel Y., Elbaz S., Budanov A., Chajut A., Kalinski H., Kamer I.,
RA Rozen A., Mor O., Keshet E., Leshkowitz D., Einat P., Skaliter R.,
RA Feinstein E.;
RT "Identification of a novel hypoxia-inducible factor 1-responsive gene,
RT RTP801, involved in apoptosis.";
RL Mol. Cell. Biol. 22:2283-2293(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Uterus;
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 INDUCTION.
RX PubMed=14646594; DOI=10.1038/emm.2003.53;
RA Kim J.-R., Lee S.-R., Chung H.J., Kim S., Baek S.-H., Kim J.H., Kim Y.-S.;
RT "Identification of amyloid beta-peptide responsive genes by cDNA microarray
RT technology: involvement of RTP801 in amyloid beta-peptide toxicity.";
RL Exp. Mol. Med. 35:403-411(2003).
RN [9]
RP FUNCTION.
RX PubMed=15545625; DOI=10.1101/gad.1256804;
RA Brugarolas J., Lei K., Hurley R.L., Manning B.D., Reiling J.H., Hafen E.,
RA Witters L.A., Ellisen L.W., Kaelin W.G. Jr.;
RT "Regulation of mTOR function in response to hypoxia by REDD1 and the
RT TSC1/TSC2 tumor suppressor complex.";
RL Genes Dev. 18:2893-2904(2004).
RN [10]
RP INDUCTION.
RX PubMed=15751966; DOI=10.1021/bi047574r;
RA Lin L., Qian Y., Shi X., Chen Y.;
RT "Induction of a cell stress response gene RTP801 by DNA damaging agent
RT methyl methanesulfonate through CCAAT/enhancer binding protein.";
RL Biochemistry 44:3909-3914(2005).
RN [11]
RP FUNCTION.
RX PubMed=15632201; DOI=10.1074/jbc.c400557200;
RA Corradetti M.N., Inoki K., Guan K.-L.;
RT "The stress-inducted proteins RTP801 and RTP801L are negative regulators of
RT the mammalian target of rapamycin pathway.";
RL J. Biol. Chem. 280:9769-9772(2005).
RN [12]
RP FUNCTION.
RX PubMed=15988001; DOI=10.1128/mcb.25.14.5834-5845.2005;
RA Sofer A., Lei K., Johannessen C.M., Ellisen L.W.;
RT "Regulation of mTOR and cell growth in response to energy stress by
RT REDD1.";
RL Mol. Cell. Biol. 25:5834-5845(2005).
RN [13]
RP INDUCTION.
RX PubMed=15592522; DOI=10.1038/sj.onc.1208236;
RA Schwarzer R., Tondera D., Arnold W., Giese K., Klippel A., Kaufmann J.;
RT "REDD1 integrates hypoxia-mediated survival signaling downstream of
RT phosphatidylinositol 3-kinase.";
RL Oncogene 24:1138-1149(2005).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17005863; DOI=10.1523/jneurosci.3292-06.2006;
RA Malagelada C., Ryu E.J., Biswas S.C., Jackson-Lewis V., Greene L.A.;
RT "RTP801 is elevated in Parkinson brain substantia nigral neurons and
RT mediates death in cellular models of Parkinson's disease by a mechanism
RT involving mammalian target of rapamycin inactivation.";
RL J. Neurosci. 26:9996-10005(2006).
RN [15]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=17379067; DOI=10.1016/j.exphem.2007.01.049;
RA Gery S., Park D.J., Vuong P.T., Virk R.K., Muller C.I., Hofmann W.-K.,
RA Koeffler H.P.;
RT "RTP801 is a novel retinoic acid-responsive gene associated with myeloid
RT differentiation.";
RL Exp. Hematol. 35:572-578(2007).
RN [16]
RP FUNCTION, UBIQUITINATION, INTERACTION WITH BTRC, IDENTIFICATION IN A
RP COMPLEX WITH CUL4A; DDB1 AND BTRC, IDENTIFICATION BY MASS SPECTROMETRY,
RP PARTIAL PROTEIN SEQUENCE, MUTAGENESIS OF SER-19; THR-23 AND THR-25, AND
RP PHOSPHORYLATION AT SER-19; THR-23; THR-25 AND SER-121.
RX PubMed=19557001; DOI=10.1038/embor.2009.93;
RA Katiyar S., Liu E., Knutzen C.A., Lang E.S., Lombardo C.R., Sankar S.,
RA Toth J.I., Petroski M.D., Ronai Z., Chiang G.G.;
RT "REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1
RT ubiquitin ligase.";
RL EMBO Rep. 10:866-872(2009).
RN [17]
RP INTERACTION WITH TXNIP, AND FUNCTION.
RX PubMed=21460850; DOI=10.1038/onc.2011.102;
RA Jin H.O., Seo S.K., Kim Y.S., Woo S.H., Lee K.H., Yi J.Y., Lee S.J.,
RA Choe T.B., Lee J.H., An S., Hong S.I., Park I.C.;
RT "TXNIP potentiates Redd1-induced mTOR suppression through stabilization of
RT Redd1.";
RL Oncogene 30:3792-3801(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 89-226, FUNCTION, SUBUNIT,
RP INDUCTION, AND MUTAGENESIS OF SER-103; ARG-133; SER-137; PRO-139; CYS-140;
RP LYS-219; LEU-221 AND TYR-222.
RX PubMed=20166753; DOI=10.1021/bi902135e;
RA Vega-Rubin-de-Celis S., Abdallah Z., Kinch L., Grishin N.V., Brugarolas J.,
RA Zhang X.;
RT "Structural analysis and functional implications of the negative mTORC1
RT regulator REDD1.";
RL Biochemistry 49:2491-2501(2010).
CC -!- FUNCTION: Regulates cell growth, proliferation and survival via
CC inhibition of the activity of the mammalian target of rapamycin complex
CC 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves
CC DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an
CC important role in responses to cellular energy levels and cellular
CC stress, including responses to hypoxia and DNA damage. Regulates
CC p53/TP53-mediated apoptosis in response to DNA damage via its effect on
CC mTORC1 activity. Its role in the response to hypoxia depends on the
CC cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes,
CC but not in hepatocytes (By similarity). Required for mTORC1-mediated
CC defense against viral protein synthesis and virus replication (By
CC similarity). Inhibits neuronal differentiation and neurite outgrowth
CC mediated by NGF via its effect on mTORC1 activity. Required for normal
CC neuron migration during embryonic brain development. Plays a role in
CC neuronal cell death. {ECO:0000250, ECO:0000269|PubMed:15545625,
CC ECO:0000269|PubMed:15632201, ECO:0000269|PubMed:15988001,
CC ECO:0000269|PubMed:17005863, ECO:0000269|PubMed:17379067,
CC ECO:0000269|PubMed:19557001, ECO:0000269|PubMed:20166753,
CC ECO:0000269|PubMed:21460850}.
CC -!- SUBUNIT: Monomer. Interacts with BTRC. Identified in a complex with
CC CUL4A, DDB1 and BTRC. Interacts with TXNIP; this inhibits the
CC proteasomal degradation of DDIT4. {ECO:0000269|PubMed:19557001,
CC ECO:0000269|PubMed:20166753, ECO:0000269|PubMed:21460850}.
CC -!- INTERACTION:
CC Q9NX09; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-715104, EBI-6425864;
CC Q9NX09; Q14145: KEAP1; NbExp=3; IntAct=EBI-715104, EBI-751001;
CC Q9NX09; P57682: KLF3; NbExp=3; IntAct=EBI-715104, EBI-8472267;
CC Q9NX09; Q9Y483-4: MTF2; NbExp=3; IntAct=EBI-715104, EBI-10698053;
CC Q9NX09; P16284: PECAM1; NbExp=3; IntAct=EBI-715104, EBI-716404;
CC Q9NX09; Q6P1K2: PMF1; NbExp=3; IntAct=EBI-715104, EBI-713832;
CC Q9NX09; P08195-4: SLC3A2; NbExp=3; IntAct=EBI-715104, EBI-12832276;
CC Q9NX09; P61086: UBE2K; NbExp=3; IntAct=EBI-715104, EBI-473850;
CC Q9NX09; P40337-2: VHL; NbExp=3; IntAct=EBI-715104, EBI-12157263;
CC Q9NX09; P58304: VSX2; NbExp=3; IntAct=EBI-715104, EBI-6427899;
CC Q9NX09; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-715104, EBI-25831733;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:12453409}.
CC -!- TISSUE SPECIFICITY: Broadly expressed, with lowest levels in brain,
CC skeletal muscle and intestine. Up-regulated in substantia nigra neurons
CC from Parkinson disease patients (at protein level).
CC {ECO:0000269|PubMed:11884613, ECO:0000269|PubMed:12453409,
CC ECO:0000269|PubMed:17005863, ECO:0000269|PubMed:17379067}.
CC -!- INDUCTION: Up-regulated in fibroblasts upon ionizing radiation, via a
CC TP53-dependent pathway. Up-regulated by TP63 in primary keratinocytes,
CC and down-regulated during keratinocyte differentiation. Up-regulated
CC upon DNA alkylation. Up-regulated by amyloid beta-peptide and retinoic
CC acid. Up-regulated by hypoxia, via a PI3K and HIF1A-dependent but
CC TP53/TP63-independent mechanism (at protein level).
CC {ECO:0000269|PubMed:11884613, ECO:0000269|PubMed:12453409,
CC ECO:0000269|PubMed:14646594, ECO:0000269|PubMed:15592522,
CC ECO:0000269|PubMed:15751966, ECO:0000269|PubMed:17379067,
CC ECO:0000269|PubMed:20166753}.
CC -!- PTM: Phosphorylated by GSK3B; this promotes proteasomal degradation.
CC {ECO:0000269|PubMed:19557001}.
CC -!- PTM: Polyubiquitinated by a DCX (DDB1-CUL4A-RBX1) E3 ubiquitin-protein
CC ligase complex with BTRC as substrate-recognition component, leading to
CC its proteasomal degradation. {ECO:0000269|PubMed:19557001}.
CC -!- SIMILARITY: Belongs to the DDIT4 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DDIT4ID45802ch10q22.html";
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DR EMBL; AY090097; AAM10442.1; -; mRNA.
DR EMBL; AF335324; AAL38424.1; -; mRNA.
DR EMBL; AL136668; CAB66603.1; -; mRNA.
DR EMBL; AK000507; BAA91214.1; -; mRNA.
DR EMBL; AL683820; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54452.1; -; Genomic_DNA.
DR EMBL; BC000708; AAH00708.1; -; mRNA.
DR EMBL; BC007714; AAH07714.1; -; mRNA.
DR EMBL; BC015236; AAH15236.1; -; mRNA.
DR CCDS; CCDS7315.1; -.
DR RefSeq; NP_061931.1; NM_019058.3.
DR PDB; 3LQ9; X-ray; 2.00 A; A/B=89-226.
DR PDB; 7MOP; EM; 3.30 A; B=1-232.
DR PDBsum; 3LQ9; -.
DR PDBsum; 7MOP; -.
DR AlphaFoldDB; Q9NX09; -.
DR SMR; Q9NX09; -.
DR BioGRID; 120028; 20.
DR CORUM; Q9NX09; -.
DR IntAct; Q9NX09; 24.
DR MINT; Q9NX09; -.
DR STRING; 9606.ENSP00000307305; -.
DR iPTMnet; Q9NX09; -.
DR PhosphoSitePlus; Q9NX09; -.
DR BioMuta; DDIT4; -.
DR DMDM; 74753036; -.
DR EPD; Q9NX09; -.
DR jPOST; Q9NX09; -.
DR MassIVE; Q9NX09; -.
DR MaxQB; Q9NX09; -.
DR PaxDb; Q9NX09; -.
DR PeptideAtlas; Q9NX09; -.
DR PRIDE; Q9NX09; -.
DR ProteomicsDB; 83020; -.
DR Antibodypedia; 29243; 334 antibodies from 37 providers.
DR DNASU; 54541; -.
DR Ensembl; ENST00000307365.4; ENSP00000307305.3; ENSG00000168209.6.
DR Ensembl; ENST00000491934.3; ENSP00000506356.1; ENSG00000168209.6.
DR GeneID; 54541; -.
DR KEGG; hsa:54541; -.
DR MANE-Select; ENST00000307365.4; ENSP00000307305.3; NM_019058.4; NP_061931.1.
DR UCSC; uc001jsx.2; human.
DR CTD; 54541; -.
DR DisGeNET; 54541; -.
DR GeneCards; DDIT4; -.
DR HGNC; HGNC:24944; DDIT4.
DR HPA; ENSG00000168209; Low tissue specificity.
DR MIM; 607729; gene.
DR neXtProt; NX_Q9NX09; -.
DR OpenTargets; ENSG00000168209; -.
DR PharmGKB; PA134977994; -.
DR VEuPathDB; HostDB:ENSG00000168209; -.
DR eggNOG; ENOG502RB72; Eukaryota.
DR GeneTree; ENSGT00530000063652; -.
DR HOGENOM; CLU_086145_1_0_1; -.
DR InParanoid; Q9NX09; -.
DR OMA; EQGKGCH; -.
DR OrthoDB; 1588396at2759; -.
DR PhylomeDB; Q9NX09; -.
DR TreeFam; TF105007; -.
DR PathwayCommons; Q9NX09; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR SignaLink; Q9NX09; -.
DR SIGNOR; Q9NX09; -.
DR BioGRID-ORCS; 54541; 23 hits in 1092 CRISPR screens.
DR ChiTaRS; DDIT4; human.
DR EvolutionaryTrace; Q9NX09; -.
DR GeneWiki; DDIT4; -.
DR GenomeRNAi; 54541; -.
DR Pharos; Q9NX09; Tbio.
DR PRO; PR:Q9NX09; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9NX09; protein.
DR Bgee; ENSG00000168209; Expressed in pericardium and 208 other tissues.
DR ExpressionAtlas; Q9NX09; baseline and differential.
DR Genevisible; Q9NX09; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0071889; F:14-3-3 protein binding; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IEA:Ensembl.
DR GO; GO:1902532; P:negative regulation of intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; ISS:UniProtKB.
DR GO; GO:0032984; P:protein-containing complex disassembly; IEA:Ensembl.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0032006; P:regulation of TOR signaling; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR Gene3D; 3.90.470.40; -; 1.
DR InterPro; IPR012918; RTP801-like.
DR InterPro; IPR038281; RTP801-like_C_sf.
DR PANTHER; PTHR12478; PTHR12478; 1.
DR Pfam; PF07809; RTP801_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Apoptosis; Cytoplasm;
KW Direct protein sequencing; Mitochondrion; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..232
FT /note="DNA damage-inducible transcript 4 protein"
FT /id="PRO_0000307197"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..66
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19557001"
FT MOD_RES 23
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19557001"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19557001"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19557001"
FT MUTAGEN 19
FT /note="S->A: Strongly inhibits proteasomal degradation."
FT /evidence="ECO:0000269|PubMed:19557001"
FT MUTAGEN 23
FT /note="T->A: Strongly inhibits proteasomal degradation.
FT Strongly inhibits proteasomal degradation; when associated
FT with A-25."
FT /evidence="ECO:0000269|PubMed:19557001"
FT MUTAGEN 25
FT /note="T->A: Strongly inhibits proteasomal degradation;
FT when associated with A-23."
FT /evidence="ECO:0000269|PubMed:19557001"
FT MUTAGEN 103
FT /note="S->L,W: No effect on inhibition of mTORC1."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 133
FT /note="R->A: No effect on inhibition of mTORC1."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 137
FT /note="S->A,D: No effect on inhibition of mTORC1."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 139
FT /note="P->A: Abolishes inhibition of mTORC1."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 140
FT /note="C->S: Mildly reduces inhibition of mTORC1."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 219
FT /note="K->A: Reduces inhibition of mTORC1. Abolishes
FT inhibition of mTORC1; when associated with A-222."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 221
FT /note="L->A: Reduces inhibition of mTORC1."
FT /evidence="ECO:0000269|PubMed:20166753"
FT MUTAGEN 222
FT /note="Y->A: Reduces inhibition of mTORC1. Abolishes
FT inhibition of mTORC1; when associated with A-219."
FT /evidence="ECO:0000269|PubMed:20166753"
FT CONFLICT 228
FT /note="L -> P (in Ref. 3; CAB66603)"
FT /evidence="ECO:0000305"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:7MOP"
FT HELIX 90..104
FT /evidence="ECO:0007829|PDB:3LQ9"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:3LQ9"
FT HELIX 121..135
FT /evidence="ECO:0007829|PDB:3LQ9"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:3LQ9"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:3LQ9"
FT STRAND 156..165
FT /evidence="ECO:0007829|PDB:3LQ9"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:3LQ9"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:3LQ9"
SQ SEQUENCE 232 AA; 25371 MW; 774E941EBDD08198 CRC64;
MPSLWDRFSS SSTSSSPSSL PRTPTPDRPP RSAWGSATRE EGFDRSTSLE SSDCESLDSS
NSGFGPEEDT AYLDGVSLPD FELLSDPEDE HLCANLMQLL QESLAQARLG SRRPARLLMP
SQLVSQVGKE LLRLAYSEPC GLRGALLDVC VEQGKSCHSV GQLALDPSLV PTFQLTLVLR
LDSRLWPKIQ GLFSSANSPF LPGFSQSLTL STGFRVIKKK LYSSEQLLIE EC
