CPLM-022299

Genbank Nucleotide ID

DNA damage-inducible transcript 4 protein

Protein Synonyms/Alias

HIF-1 responsive protein RTP801; Protein regulated in development and DNA damage response 1; REDD-1

Homo sapiens (Human)

Position	Peptide	Type	References
129	QLVSQVGKELLRLAY	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]
188	LDSRLWPKIQGLFSS	ubiquitination	[2]
218	STGFRVIKKKLYSSE	ubiquitination	[6]
219	TGFRVIKKKLYSSEQ	ubiquitination	[6, 11]
220	GFRVIKKKLYSSEQL	ubiquitination	[6, 8, 11]

[1] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[2] A data set of human endogenous protein ubiquitination sites.
Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
[3] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[6] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[8] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[9] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[11] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[12] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[13] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[14] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

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.

MOD_RES 19 19 Phosphoserine.
MOD_RES 23 23 Phosphothreonine.
MOD_RES 25 25 Phosphothreonine.
MOD_RES 121 121 Phosphoserine.

3D-structure; Antiviral defense; Apoptosis; Complete proteome; Cytoplasm; Direct protein sequencing; Mitochondrion; Phosphoprotein; Reference proteome; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
GO:0007420; P:brain development; ISS:UniProtKB.
GO:0008283; P:cell proliferation; ISS:UniProtKB.
GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
GO:0045820; P:negative regulation of glycolysis; IEA:Compara.
GO:0010741; P:negative regulation of intracellular protein kinase cascade; ISS:UniProtKB.
GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
GO:0032007; P:negative regulation of TOR signaling cascade; IMP:UniProtKB.
GO:0030182; P:neuron differentiation; ISS:UniProtKB.
GO:0001764; P:neuron migration; ISS:UniProtKB.
GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
GO:1901216; P:positive regulation of neuron death; ISS:UniProtKB.
GO:0043241; P:protein complex disassembly; IEA:Compara.
GO:0072593; P:reactive oxygen species metabolic process; IEA:Compara.
GO:0001666; P:response to hypoxia; IDA:UniProtKB.

IPR012918; RTP801-like.