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UniProtKB - Q8N122 (RPTOR_HUMAN)

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Protein

Regulatory-associated protein of mTOR

Gene

RPTOR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  • 14-3-3 protein binding Source: UniProtKB
  • protein binding, bridging Source: WormBase
  • protein-containing complex binding Source: UniProtKB
  • protein kinase activator activity Source: WormBase
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase inhibitor activity Source: WormBase
  • RNA polymerase III type 1 promoter DNA binding Source: UniProtKB
  • RNA polymerase III type 2 promoter DNA binding Source: UniProtKB
  • RNA polymerase III type 3 promoter DNA binding Source: UniProtKB
  • TFIIIC-class transcription factor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cell cycle arrest Source: Reactome
  • cellular response to amino acid stimulus Source: UniProtKB
  • cellular response to leucine Source: CAFA
  • cellular response to nutrient levels Source: UniProtKB
  • cellular response to starvation Source: GO_Central
  • positive regulation of cell growth Source: ParkinsonsUK-UCL
  • positive regulation of endothelial cell proliferation Source: Ensembl
  • positive regulation of G1/S transition of mitotic cell cycle Source: ParkinsonsUK-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
  • positive regulation of transcription by RNA polymerase III Source: UniProtKB
  • regulation of autophagy Source: GO_Central
  • regulation of cell growth Source: UniProtKB
  • regulation of cell size Source: UniProtKB
  • regulation of cellular response to heat Source: Reactome
  • regulation of macroautophagy Source: Reactome
  • TORC1 signaling Source: WormBase
  • TOR signaling Source: UniProtKB
View the complete GO annotation on QuickGO ...

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
R-HSA-165159 mTOR signalling
R-HSA-166208 mTORC1-mediated signalling
R-HSA-3371571 HSF1-dependent transactivation
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-8943724 Regulation of PTEN gene transcription
SABIO-RKiQ8N122
SignaLinkiQ8N122
SIGNORiQ8N122

Names & Taxonomyi

Protein namesi
Recommended name:
Regulatory-associated protein of mTOR
Short name:
Raptor
Alternative name(s):
p150 target of rapamycin (TOR)-scaffold protein
Gene namesi
Name:RPTOR
Synonyms:KIAA1303, RAPTOR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141564.13
HGNCiHGNC:30287 RPTOR
MIMi607130 gene
neXtProtiNX_Q8N122

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi722S → A: Abolishes AMPK-mediated phosphorylation; when associated with A-792. 1 Publication1
Mutagenesisi792S → A: Abolishes AMPK-mediated phosphorylation; when associated with A-722. 1 Publication1

Organism-specific databases

DisGeNETi57521
OpenTargetsiENSG00000141564
PharmGKBiPA165432629

Chemistry databases

ChEMBLiCHEMBL3120040

Polymorphism and mutation databases

BioMutaiRPTOR
DMDMi46577501

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000512001 – 1335Regulatory-associated protein of mTORAdd BLAST1335

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei696Phosphoserine; by MAPK8Combined sources2 Publications1
Modified residuei706Phosphothreonine; by MAPK82 Publications1
Modified residuei719Phosphoserine; by RPS6KA1Combined sources1 Publication1
Modified residuei721Phosphoserine; by RPS6KA11 Publication1
Modified residuei722Phosphoserine; by AMPK and RPS6KA1Combined sources2 Publications1
Modified residuei738PhosphoserineCombined sources1
Modified residuei792Phosphoserine; by AMPK1 Publication1
Modified residuei855Phosphoserine1 Publication1
Modified residuei859Phosphoserine; by MTORCombined sources1 Publication1
Modified residuei863Phosphoserine; by MAPK8 and MTORCombined sources2 Publications1
Modified residuei865PhosphothreonineCombined sources1
Modified residuei877PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Insulin-stimulated phosphorylation at Ser-863 by MTOR and MAPK8 up-regulates mTORC1 activity. Osmotic stress also induces phosphorylation at Ser-696, Thr-706 and Ser-863 by MAPK8. Ser-863 phosphorylation is required for phosphorylation at Ser-855 and Ser-859. In response to nutrient limitation, phosphorylated by AMPK; phosphorylation promotes interaction with 14-3-3 proteins, leading to negative regulation of the mTORC1 complex. In response to growth factors, phosphorylated at Ser-719, Ser-721 and Ser-722 by RPS6KA1, which stimulates mTORC1 activity.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8N122
MaxQBiQ8N122
PaxDbiQ8N122
PeptideAtlasiQ8N122
PRIDEiQ8N122
ProteomicsDBi71521
71522 [Q8N122-2]

PTM databases

iPTMnetiQ8N122
PhosphoSitePlusiQ8N122

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle, and in a lesser extent in brain, lung, small intestine, kidney and placenta. Isoform 3 is widely expressed, with highest levels in nasal mucosa and pituitary and lowest in spleen.2 Publications

Gene expression databases

BgeeiENSG00000141564
ExpressionAtlasiQ8N122 baseline and differential
GenevisibleiQ8N122 HS

Organism-specific databases

HPAiCAB013514
HPA064306

Interactioni

Subunit structurei

Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR (PubMed:12150925, PubMed:12408816, PubMed:17386266, PubMed:25940091). mTORC1 binds to and is inhibited by FKBP12-rapamycin (PubMed:12408816, PubMed:15066126). Binds directly to 4EBP1 and RPS6KB1 independently of its association with MTOR (PubMed:12150925, PubMed:12150926). Binds preferentially to poorly or non-phosphorylated forms of EIF4EBP1, and this binding is critical to the ability of MTOR to catalyze phosphorylation (PubMed:12747827). Forms a complex with MTOR under both leucine-rich and -poor conditions. Interacts with ULK1 in a nutrient-dependent manner; the interaction is reduced during starvation (PubMed:19211835). Interacts (when phosphorylated by AMPK) with 14-3-3 protein, leading to inhibition of its activity (PubMed:18439900). Interacts with SPAG5; SPAG5 competes with MTOR for RPTOR-binding, resulting in decreased mTORC1 formation. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). Interacts with G3BP1. The complex formed with G3BP1 AND SPAG5 is increased by oxidative stress (PubMed:23953116). Interacts with HTR6 (PubMed:23027611). Interacts with PIH1D1 (PubMed:24036451). Interacts with LARP1 (PubMed:25940091). Interacts with BRAT1 (PubMed:25657994).13 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • 14-3-3 protein binding Source: UniProtKB
  • protein binding, bridging Source: WormBase
  • protein kinase binding Source: UniProtKB
  • TFIIIC-class transcription factor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi121582, 137 interactors
CORUMiQ8N122
DIPiDIP-39482N
ELMiQ8N122
IntActiQ8N122, 69 interactors
MINTiQ8N122
STRINGi9606.ENSP00000307272

Structurei

3D structure databases

ProteinModelPortaliQ8N122
SMRiQ8N122
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati1020 – 1061WD 1Add BLAST42
Repeati1065 – 1106WD 2Add BLAST42
Repeati1121 – 1160WD 3Add BLAST40
Repeati1164 – 1203WD 4Add BLAST40
Repeati1209 – 1249WD 5Add BLAST41
Repeati1251 – 1291WD 6Add BLAST41
Repeati1299 – 1335WD 7Add BLAST37

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi881 – 887Poly-Ser7

Sequence similaritiesi

Belongs to the WD repeat RAPTOR family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG1517 Eukaryota
ENOG410XQKJ LUCA
GeneTreeiENSGT00640000091541
HOGENOMiHOG000184479
HOVERGENiHBG059496
InParanoidiQ8N122
KOiK07204
OMAiYIHLAAC
OrthoDBiEOG091G00H9
PhylomeDBiQ8N122
TreeFamiTF105729

Family and domain databases

Gene3Di1.25.10.10, 1 hit
2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR000357 HEAT
IPR004083 Raptor
IPR029347 Raptor_N
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR12848 PTHR12848, 1 hit
PfamiView protein in Pfam
PF02985 HEAT, 1 hit
PF14538 Raptor_N, 1 hit
PF00400 WD40, 1 hit
SMARTiView protein in SMART
SM01302 Raptor_N, 1 hit
SM00320 WD40, 7 hits
SUPFAMiSSF48371 SSF48371, 2 hits
SSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS50294 WD_REPEATS_REGION, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N122-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MESEMLQSPL LGLGEEDEAD LTDWNLPLAF MKKRHCEKIE GSKSLAQSWR 
        60         70         80         90        100
MKDRMKTVSV ALVLCLNVGV DPPDVVKTTP CARLECWIDP LSMGPQKALE 
       110        120        130        140        150
TIGANLQKQY ENWQPRARYK QSLDPTVDEV KKLCTSLRRN AKEERVLFHY 
       160        170        180        190        200
NGHGVPRPTV NGEVWVFNKN YTQYIPLSIY DLQTWMGSPS IFVYDCSNAG 
       210        220        230        240        250
LIVKSFKQFA LQREQELEVA AINPNHPLAQ MPLPPSMKNC IQLAACEATE 
       260        270        280        290        300
LLPMIPDLPA DLFTSCLTTP IKIALRWFCM QKCVSLVPGV TLDLIEKIPG 
       310        320        330        340        350
RLNDRRTPLG ELNWIFTAIT DTIAWNVLPR DLFQKLFRQD LLVASLFRNF 
       360        370        380        390        400
LLAERIMRSY NCTPVSSPRL PPTYMHAMWQ AWDLAVDICL SQLPTIIEEG 
       410        420        430        440        450
TAFRHSPFFA EQLTAFQVWL TMGVENRNPP EQLPIVLQVL LSQVHRLRAL 
       460        470        480        490        500
DLLGRFLDLG PWAVSLALSV GIFPYVLKLL QSSARELRPL LVFIWAKILA 
       510        520        530        540        550
VDSSCQADLV KDNGHKYFLS VLADPYMPAE HRTMTAFILA VIVNSYHTGQ 
       560        570        580        590        600
EACLQGNLIA ICLEQLNDPH PLLRQWVAIC LGRIWQNFDS ARWCGVRDSA 
       610        620        630        640        650
HEKLYSLLSD PIPEVRCAAV FALGTFVGNS AERTDHSTTI DHNVAMMLAQ 
       660        670        680        690        700
LVSDGSPMVR KELVVALSHL VVQYESNFCT VALQFIEEEK NYALPSPATT 
       710        720        730        740        750
EGGSLTPVRD SPCTPRLRSV SSYGNIRAVA TARSLNKSLQ NLSLTEESGG 
       760        770        780        790        800
AVAFSPGNLS TSSSASSTLG SPENEEHILS FETIDKMRRA SSYSSLNSLI 
       810        820        830        840        850
GVSFNSVYTQ IWRVLLHLAA DPYPEVSDVA MKVLNSIAYK ATVNARPQRV 
       860        870        880        890        900
LDTSSLTQSA PASPTNKGVH IHQAGGSPPA SSTSSSSLTN DVAKQPVSRD 
       910        920        930        940        950
LPSGRPGTTG PAGAQYTPHS HQFPRTRKMF DKGPEQTADD ADDAAGHKSF 
       960        970        980        990       1000
ISATVQTGFC DWSARYFAQP VMKIPEEHDL ESQIRKEREW RFLRNSRVRR 
      1010       1020       1030       1040       1050
QAQQVIQKGI TRLDDQIFLN RNPGVPSVVK FHPFTPCIAV ADKDSICFWD 
      1060       1070       1080       1090       1100
WEKGEKLDYF HNGNPRYTRV TAMEYLNGQD CSLLLTATDD GAIRVWKNFA 
      1110       1120       1130       1140       1150
DLEKNPEMVT AWQGLSDMLP TTRGAGMVVD WEQETGLLMS SGDVRIVRIW 
      1160       1170       1180       1190       1200
DTDREMKVQD IPTGADSCVT SLSCDSHRSL IVAGLGDGSI RVYDRRMALS 
      1210       1220       1230       1240       1250
ECRVMTYREH TAWVVKASLQ KRPDGHIVSV SVNGDVRIFD PRMPESVNVL 
      1260       1270       1280       1290       1300
QIVKGLTALD IHPQADLIAC GSVNQFTAIY NSSGELINNI KYYDGFMGQR 
      1310       1320       1330 
VGAISCLAFH PHWPHLAVGS NDYYISVYSV EKRVR
Length:1,335
Mass (Da):149,038
Last modified:October 1, 2002 - v1
Checksum:i688ED1943F45045A
GO
Isoform 2 (identifier: Q8N122-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     380-1335: Missing.

Show »
Length:379
Mass (Da):43,256
Checksum:iD67B01D4E68E859E
GO
Isoform 3 (identifier: Q8N122-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     504-661: Missing.

Show »
Length:1,177
Mass (Da):131,515
Checksum:i1CE0DA04E72105B2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti217 – 218LE → RQ in BAA92541 (PubMed:10718198).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010174380 – 1335Missing in isoform 2. 1 PublicationAdd BLAST956
Alternative sequenceiVSP_054042504 – 661Missing in isoform 3. 1 PublicationAdd BLAST158

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY090663 mRNA Translation: AAM09075.1
AB082951 mRNA Translation: BAC06490.1
AC016245 Genomic DNA No translation available.
AC109327 Genomic DNA No translation available.
AC127496 Genomic DNA No translation available.
AC133012 Genomic DNA No translation available.
CH471099 Genomic DNA Translation: EAW89618.1
BC025180 mRNA Translation: AAH25180.1
BC033258 mRNA Translation: AAH33258.1
BC064515 mRNA Translation: AAH64515.1
BC136652 mRNA Translation: AAI36653.1
BC136654 mRNA Translation: AAI36655.1
AB037724 mRNA Translation: BAA92541.1
GQ183898 mRNA Translation: ACS44766.1
CCDSiCCDS11773.1 [Q8N122-1]
CCDS54175.1 [Q8N122-3]
RefSeqiNP_001156506.1, NM_001163034.1 [Q8N122-3]
NP_065812.1, NM_020761.2 [Q8N122-1]
UniGeneiHs.133044

Genome annotation databases

EnsembliENST00000306801; ENSP00000307272; ENSG00000141564 [Q8N122-1]
ENST00000544334; ENSP00000442479; ENSG00000141564 [Q8N122-3]
ENST00000570891; ENSP00000460136; ENSG00000141564 [Q8N122-2]
GeneIDi57521
KEGGihsa:57521
UCSCiuc002jys.5 human [Q8N122-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRPTOR_HUMAN
AccessioniPrimary (citable) accession number: Q8N122
Secondary accession number(s): B2RN36
, C6KEF2, F5H7J5, Q8N4V9, Q8TB32, Q9P2P3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: October 1, 2002
Last modified: July 18, 2018
This is version 166 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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