DNA damage-inducible transcript 4 protein

Details

Name
DNA damage-inducible transcript 4 protein
Synonyms
  • HIF-1 responsive protein RTP801
  • Protein regulated in development and DNA damage response 1
  • REDD-1
  • REDD1
  • RTP801
Gene Name
DDIT4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0017105|DNA damage-inducible transcript 4 protein
MPSLWDRFSSSSTSSSPSSLPRTPTPDRPPRSAWGSATREEGFDRSTSLESSDCESLDSS
NSGFGPEEDTAYLDGVSLPDFELLSDPEDEHLCANLMQLLQESLAQARLGSRRPARLLMP
SQLVSQVGKELLRLAYSEPCGLRGALLDVCVEQGKSCHSVGQLALDPSLVPTFQLTLVLR
LDSRLWPKIQGLFSSANSPFLPGFSQSLTLSTGFRVIKKKLYSSEQLLIEEC
Number of residues
232
Molecular Weight
25370.225
Theoretical pI
4.61
GO Classification
Processes
brain development / cell proliferation / defense response to virus / gene expression / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / negative regulation of glycolytic process / negative regulation of intracellular signal transduction / negative regulation of peptidyl-serine phosphorylation / negative regulation of peptidyl-threonine phosphorylation / negative regulation of TOR signaling / neuron differentiation / neuron migration / neurotrophin TRK receptor signaling pathway / positive regulation of neuron death / protein complex disassembly / reactive oxygen species metabolic process / response to hypoxia / transcription initiation from RNA polymerase II promoter
Components
cytoplasm / cytosol / intracellular / mitochondrion
General Function
Not Available
Specific Function
Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes (By similarity). Required for mTORC1-mediated defense against viral protein synthesis and virus replication (By similarity). Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion
Gene sequence
>lcl|BSEQ0017106|DNA damage-inducible transcript 4 protein (DDIT4)
ATGCCTAGCCTTTGGGACCGCTTCTCGTCGTCGTCCACCTCCTCTTCGCCCTCGTCCTTG
CCCCGAACTCCCACCCCAGATCGGCCGCCGCGCTCAGCCTGGGGGTCGGCGACCCGGGAG
GAGGGGTTTGACCGCTCCACGAGCCTGGAGAGCTCGGACTGCGAGTCCCTGGACAGCAGC
AACAGTGGCTTCGGGCCGGAGGAAGACACGGCTTACCTGGATGGGGTGTCGTTGCCCGAC
TTCGAGCTGCTCAGTGACCCTGAGGATGAACACTTGTGTGCCAACCTGATGCAGCTGCTG
CAGGAGAGCCTGGCCCAGGCGCGGCTGGGCTCTCGACGCCCTGCGCGCCTGCTGATGCCT
AGCCAGTTGGTAAGCCAGGTGGGCAAAGAACTACTGCGCCTGGCCTACAGCGAGCCGTGC
GGCCTGCGGGGGGCGCTGCTGGACGTCTGCGTGGAGCAGGGCAAGAGCTGCCACAGCGTG
GGCCAGCTGGCACTCGACCCCAGCCTGGTGCCCACCTTCCAGCTGACCCTCGTGCTGCGC
CTGGACTCACGACTCTGGCCCAAGATCCAGGGGCTGTTTAGCTCCGCCAACTCTCCCTTC
CTCCCTGGCTTCAGCCAGTCCCTGACGCTGAGCACTGGCTTCCGAGTCATCAAGAAGAAG
CTGTACAGCTCGGAACAGCTGCTCATTGAGGAGTGTTGA
Chromosome Location
10
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ9NX09
UniProtKB Entry NameDDIT4_HUMAN
GenBank Gene IDBC015236
GenAtlas IDDDIT4
HGNC IDHGNC:24944
General References
  1. Ellisen LW, Ramsayer KD, Johannessen CM, Yang A, Beppu H, Minda K, Oliner JD, McKeon F, Haber DA: REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species. Mol Cell. 2002 Nov;10(5):995-1005. [Article]
  2. Shoshani T, Faerman A, Mett I, Zelin E, Tenne T, Gorodin S, Moshel Y, Elbaz S, Budanov A, Chajut A, Kalinski H, Kamer I, Rozen A, Mor O, Keshet E, Leshkowitz D, Einat P, Skaliter R, Feinstein E: Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol Cell Biol. 2002 Apr;22(7):2283-93. [Article]
  3. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. [Article]
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  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Kim JR, Lee SR, Chung HJ, Kim S, Baek SH, Kim JH, Kim YS: Identification of amyloid beta-peptide responsive genes by cDNA microarray technology: involvement of RTP801 in amyloid beta-peptide toxicity. Exp Mol Med. 2003 Oct 31;35(5):403-11. [Article]
  8. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG Jr: Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 2004 Dec 1;18(23):2893-904. Epub 2004 Nov 15. [Article]
  9. Lin L, Qian Y, Shi X, Chen Y: Induction of a cell stress response gene RTP801 by DNA damaging agent methyl methanesulfonate through CCAAT/enhancer binding protein. Biochemistry. 2005 Mar 15;44(10):3909-14. [Article]
  10. Corradetti MN, Inoki K, Guan KL: The stress-inducted proteins RTP801 and RTP801L are negative regulators of the mammalian target of rapamycin pathway. J Biol Chem. 2005 Mar 18;280(11):9769-72. Epub 2005 Jan 4. [Article]
  11. Sofer A, Lei K, Johannessen CM, Ellisen LW: Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol Cell Biol. 2005 Jul;25(14):5834-45. [Article]
  12. Schwarzer R, Tondera D, Arnold W, Giese K, Klippel A, Kaufmann J: REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase. Oncogene. 2005 Feb 10;24(7):1138-49. [Article]
  13. Malagelada C, Ryu EJ, Biswas SC, Jackson-Lewis V, Greene LA: RTP801 is elevated in Parkinson brain substantia nigral neurons and mediates death in cellular models of Parkinson's disease by a mechanism involving mammalian target of rapamycin inactivation. J Neurosci. 2006 Sep 27;26(39):9996-10005. [Article]
  14. Gery S, Park DJ, Vuong PT, Virk RK, Muller CI, Hofmann WK, Koeffler HP: RTP801 is a novel retinoic acid-responsive gene associated with myeloid differentiation. Exp Hematol. 2007 Apr;35(4):572-8. [Article]
  15. Katiyar S, Liu E, Knutzen CA, Lang ES, Lombardo CR, Sankar S, Toth JI, Petroski MD, Ronai Z, Chiang GG: REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase. EMBO Rep. 2009 Aug;10(8):866-72. doi: 10.1038/embor.2009.93. Epub 2009 Jun 26. [Article]
  16. Jin HO, Seo SK, Kim YS, Woo SH, Lee KH, Yi JY, Lee SJ, Choe TB, Lee JH, An S, Hong SI, Park IC: TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1. Oncogene. 2011 Sep 1;30(35):3792-801. doi: 10.1038/onc.2011.102. Epub 2011 Apr 4. [Article]
  17. Vega-Rubin-de-Celis S, Abdallah Z, Kinch L, Grishin NV, Brugarolas J, Zhang X: Structural analysis and functional implications of the negative mTORC1 regulator REDD1. Biochemistry. 2010 Mar 23;49(11):2491-501. doi: 10.1021/bi902135e. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails