DDIT4_RAT
ID DDIT4_RAT Reviewed; 229 AA.
AC Q8VHZ9;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 25-MAY-2022, entry version 92.
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 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], AND INDUCTION BY HYPOXIA.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [3]
RP INDUCTION.
RX PubMed=15452091; DOI=10.1167/iovs.04-0052;
RA Brafman A., Mett I., Shafir M., Gottlieb H., Damari G., Gozlan-Kelner S.,
RA Vishnevskia-Dai V., Skaliter R., Einat P., Faerman A., Feinstein E.,
RA Shoshani T.;
RT "Inhibition of oxygen-induced retinopathy in RTP801-deficient mice.";
RL Invest. Ophthalmol. Vis. Sci. 45:3796-3805(2004).
RN [4]
RP INDUCTION.
RX PubMed=17074751; DOI=10.1074/jbc.m610023200;
RA Wang H., Kubica N., Ellisen L.W., Jefferson L.S., Kimball S.R.;
RT "Dexamethasone represses signaling through the mammalian target of
RT rapamycin in muscle cells by enhancing expression of REDD1.";
RL J. Biol. Chem. 281:39128-39134(2006).
RN [5]
RP INDUCTION, AND FUNCTION.
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 [6]
RP FUNCTION.
RX PubMed=19118169; DOI=10.1523/jneurosci.3928-08.2008;
RA Malagelada C., Jin Z.H., Greene L.A.;
RT "RTP801 is induced in Parkinson's disease and mediates neuron death by
RT inhibiting Akt phosphorylation/activation.";
RL J. Neurosci. 28:14363-14371(2008).
RN [7]
RP FUNCTION.
RX PubMed=21368030; DOI=10.1523/jneurosci.4011-10.2011;
RA Malagelada C., Lopez-Toledano M.A., Willett R.T., Jin Z.H., Shelanski M.L.,
RA Greene L.A.;
RT "RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron
RT migration.";
RL J. Neurosci. 31:3186-3196(2011).
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. Required for mTORC1-mediated defense against
CC viral protein synthesis and virus replication (By similarity). Inhibits
CC neuronal differentiation and neurite outgrowth mediated by NGF via its
CC effect on mTORC1 activity. Required for normal neuron migration during
CC embryonic brain development. Plays a role in neuronal cell death.
CC {ECO:0000250, ECO:0000269|PubMed:17005863, ECO:0000269|PubMed:19118169,
CC ECO:0000269|PubMed:21368030}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000250}.
CC -!- INDUCTION: Strongly up-regulated by hypoxia. Up-regulated by
CC dexamethasone in skeletal muscles. Up-regulated in various cellular
CC models of Parkinson disease (at protein level).
CC {ECO:0000269|PubMed:11884613, ECO:0000269|PubMed:15452091,
CC ECO:0000269|PubMed:17005863, ECO:0000269|PubMed:17074751}.
CC -!- PTM: Phosphorylated by GSK3B; this promotes proteasomal degradation.
CC {ECO:0000250}.
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:0000250}.
CC -!- SIMILARITY: Belongs to the DDIT4 family. {ECO:0000305}.
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DR EMBL; AF334162; AAL38423.1; -; mRNA.
DR EMBL; BC062021; AAH62021.1; -; mRNA.
DR RefSeq; NP_543182.1; NM_080906.2.
DR AlphaFoldDB; Q8VHZ9; -.
DR SMR; Q8VHZ9; -.
DR STRING; 10116.ENSRNOP00000000703; -.
DR PhosphoSitePlus; Q8VHZ9; -.
DR PaxDb; Q8VHZ9; -.
DR GeneID; 140942; -.
DR KEGG; rno:140942; -.
DR UCSC; RGD:621731; rat.
DR CTD; 54541; -.
DR RGD; 621731; Ddit4.
DR eggNOG; ENOG502RB72; Eukaryota.
DR InParanoid; Q8VHZ9; -.
DR OrthoDB; 1588396at2759; -.
DR PhylomeDB; Q8VHZ9; -.
DR Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR PRO; PR:Q8VHZ9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IDA:RGD.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
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; ISO:RGD.
DR GO; GO:1902532; P:negative regulation of intracellular signal transduction; IMP:UniProtKB.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IMP:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0032984; P:protein-containing complex disassembly; ISO:RGD.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0032006; P:regulation of TOR signaling; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
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 Antiviral defense; Apoptosis; Cytoplasm; Mitochondrion; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..229
FT /note="DNA damage-inducible transcript 4 protein"
FT /id="PRO_0000307199"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..64
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NX09"
FT MOD_RES 20
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NX09"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NX09"
SQ SEQUENCE 229 AA; 24885 MW; 6513055142D7F675 CRC64;
MPSLWDRFSS SSSSSSSSRT PAADRPPRSA WGSAAREEGL DRCASLESSD CESLDSSNSG
FGPEEDSSYL DGVSLPDFEL LSDPEDEHLC ANLMQLLQES LSQARLGSRR PARLLMPSQL
LSQVGKELLR LAYSEPCGLR GALLDVCVEQ GKSCHSVAQL ALDPSLVPTF QLTLVLRLDS
RLWPKIQGLL SSANSSLVPG YSQSLTLSTG FRVIKKKLYS SEQLLIEEC
