Hmdb loader
Identification
HMDB Protein ID HMDBP13901
Secondary Accession Numbers None
Name Regulatory-associated protein of mTOR
Synonyms
  1. Raptor
  2. p150 target of rapamycin (TOR)-scaffold protein
Gene Name RPTOR
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis. mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD) (By similarity).
Pathways
  • AMPK signaling pathway
  • Autophagy - animal
  • Autophagy - other
  • Insulin signaling pathway
  • Longevity regulating pathway
  • Longevity regulating pathway - multiple species
  • MicroRNAs in cancer
  • mTOR signaling pathway
  • PI3K-Akt signaling pathway
  • Shigellosis
  • Thermogenesis
Reactions Not Available
GO Classification
Biological Process
regulation of cell growth
response to xenobiotic stimulus
cell cycle arrest
cellular response to amino acid stimulus
regulation of autophagy
social behavior
positive regulation of G1/S transition of mitotic cell cycle
positive regulation of peptidyl-threonine phosphorylation
positive regulation of TOR signaling
positive regulation of protein serine/threonine kinase activity
viral reproduction
positive regulation of transcription from RNA polymerase III promoter
regulation of cell size
positive regulation of cell growth
cellular response to starvation
cellular response to amino acid starvation
cellular response to leucine
cellular response to nutrient levels
regulation of macroautophagy
TOR signaling
TORC1 signaling
positive regulation of endothelial cell proliferation
positive regulation of peptidyl-serine phosphorylation
regulation of cellular response to heat
Cellular Component
cytosol
cytoplasm
dendrite
cytoplasmic stress granule
nucleoplasm
lysosome
neuronal cell body
TORC1 complex
lysosomal membrane
Molecular Function
protein kinase binding
protein-containing complex binding
14-3-3 protein binding
protein serine/threonine kinase inhibitor activity
RNA polymerase III type 1 promoter sequence-specific DNA binding
RNA polymerase III type 2 promoter sequence-specific DNA binding
RNA polymerase III type 3 promoter sequence-specific DNA binding
TFIIIC-class transcription factor complex binding
protein kinase activator activity
protein-macromolecule adaptor activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 1335
Molecular Weight 149036.17
Theoretical pI 6.882
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8N122
UniProtKB/Swiss-Prot Entry Name RPTOR_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. 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. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  5. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  6. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  7. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  8. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  9. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [PubMed:16625196 ]
  10. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  11. Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O: Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Feb 28;7(1):65-73. [PubMed:10718198 ]
  12. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N: Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009 Apr;20(7):1981-91. doi: 10.1091/mbc.E08-12-1248. Epub 2009 Feb 11. [PubMed:19211835 ]
  13. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K: Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002 Jul 26;110(2):177-89. [PubMed:12150926 ]
  14. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM: mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 2002 Jul 26;110(2):163-75. [PubMed:12150925 ]
  15. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN: Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. 2002 Sep;10(3):457-68. [PubMed:12408816 ]
  16. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231 ]
  17. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  18. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460 ]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569 ]
  20. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692 ]
  21. Sun C, Southard C, Di Rienzo A: Characterization of a novel splicing variant in the RAPTOR gene. Mutat Res. 2009 Mar 9;662(1-2):88-92. doi: 10.1016/j.mrfmmm.2009.01.001. [PubMed:19388141 ]
  22. Schalm SS, Fingar DC, Sabatini DM, Blenis J: TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol. 2003 May 13;13(10):797-806. doi: 10.1016/s0960-9822(03)00329-4. [PubMed:12747827 ]
  23. Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, Avruch J, Yonezawa K: Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells. 2004 Apr;9(4):359-66. doi: 10.1111/j.1356-9597.2004.00727.x. [PubMed:15066126 ]
  24. Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM: PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell. 2007 Mar 23;25(6):903-15. doi: 10.1016/j.molcel.2007.03.003. [PubMed:17386266 ]
  25. Carriere A, Cargnello M, Julien LA, Gao H, Bonneil E, Thibault P, Roux PP: Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biol. 2008 Sep 9;18(17):1269-77. doi: 10.1016/j.cub.2008.07.078. Epub 2008 Aug 21. [PubMed:18722121 ]
  26. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ: AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008 Apr 25;30(2):214-26. doi: 10.1016/j.molcel.2008.03.003. [PubMed:18439900 ]
  27. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM: Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr 8. [PubMed:20381137 ]
  28. Foster KG, Acosta-Jaquez HA, Romeo Y, Ekim B, Soliman GA, Carriere A, Roux PP, Ballif BA, Fingar DC: Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation. J Biol Chem. 2010 Jan 1;285(1):80-94. doi: 10.1074/jbc.M109.029637. Epub 2009 Oct 28. [PubMed:19864431 ]
  29. Meffre J, Chaumont-Dubel S, Mannoury la Cour C, Loiseau F, Watson DJ, Dekeyne A, Seveno M, Rivet JM, Gaven F, Deleris P, Herve D, Fone KC, Bockaert J, Millan MJ, Marin P: 5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia. EMBO Mol Med. 2012 Oct;4(10):1043-56. doi: 10.1002/emmm.201201410. [PubMed:23027611 ]
  30. Kwak D, Choi S, Jeong H, Jang JH, Lee Y, Jeon H, Lee MN, Noh J, Cho K, Yoo JS, Hwang D, Suh PG, Ryu SH: Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal Kinase (JNK)-mediated Raptor protein phosphorylation. J Biol Chem. 2012 May 25;287(22):18398-407. doi: 10.1074/jbc.M111.326538. Epub 2012 Apr 4. [PubMed:22493283 ]
  31. Thedieck K, Holzwarth B, Prentzell MT, Boehlke C, Klasener K, Ruf S, Sonntag AG, Maerz L, Grellscheid SN, Kremmer E, Nitschke R, Kuehn EW, Jonker JW, Groen AK, Reth M, Hall MN, Baumeister R: Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells. Cell. 2013 Aug 15;154(4):859-74. doi: 10.1016/j.cell.2013.07.031. [PubMed:23953116 ]
  32. Kamano Y, Saeki M, Egusa H, Kakihara Y, Houry WA, Yatani H, Kamisaki Y: PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription. FEBS Lett. 2013 Oct 11;587(20):3303-8. doi: 10.1016/j.febslet.2013.09.001. Epub 2013 Sep 11. [PubMed:24036451 ]
  33. Cardenas-Rodriguez M, Irigoin F, Osborn DP, Gascue C, Katsanis N, Beales PL, Badano JL: The Bardet-Biedl syndrome-related protein CCDC28B modulates mTORC2 function and interacts with SIN1 to control cilia length independently of the mTOR complex. Hum Mol Genet. 2013 Oct 15;22(20):4031-42. doi: 10.1093/hmg/ddt253. Epub 2013 May 31. [PubMed:23727834 ]
  34. Fonseca BD, Zakaria C, Jia JJ, Graber TE, Svitkin Y, Tahmasebi S, Healy D, Hoang HD, Jensen JM, Diao IT, Lussier A, Dajadian C, Padmanabhan N, Wang W, Matta-Camacho E, Hearnden J, Smith EM, Tsukumo Y, Yanagiya A, Morita M, Petroulakis E, Gonzalez JL, Hernandez G, Alain T, Damgaard CK: La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). J Biol Chem. 2015 Jun 26;290(26):15996-6020. doi: 10.1074/jbc.M114.621730. Epub 2015 May 4. [PubMed:25940091 ]
  35. David-Morrison G, Xu Z, Rui YN, Charng WL, Jaiswal M, Yamamoto S, Xiong B, Zhang K, Sandoval H, Duraine L, Zuo Z, Zhang S, Bellen HJ: WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes. Dev Cell. 2016 Jan 25;36(2):139-51. doi: 10.1016/j.devcel.2015.12.019. [PubMed:26812014 ]
  36. Meade N, Furey C, Li H, Verma R, Chai Q, Rollins MG, DiGiuseppe S, Naghavi MH, Walsh D: Poxviruses Evade Cytosolic Sensing through Disruption of an mTORC1-mTORC2 Regulatory Circuit. Cell. 2018 Aug 23;174(5):1143-1157.e17. doi: 10.1016/j.cell.2018.06.053. Epub 2018 Aug 2. [PubMed:30078703 ]
  37. Csukasi F, Duran I, Barad M, Barta T, Gudernova I, Trantirek L, Martin JH, Kuo CY, Woods J, Lee H, Cohn DH, Krejci P, Krakow D: The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR signaling. Sci Transl Med. 2018 Sep 19;10(459). pii: 10/459/eaat9356. doi: 10.1126/scitranslmed.aat9356. [PubMed:30232230 ]