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Reviewed, UniProtKB/Swiss-Prot P42346 (FRAP_RAT)

Last modified November 3, 2009. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Serine/threonine-protein kinase mTOR
    EC=2.7.11.1
Alternative name(s):
    Mammalian target of rapamycin
      Short name=mTOR
    FKBP12-rapamycin complex-associated protein
    FK506-binding protein 12-rapamycin complex-associated protein 1
    Rapamycin target protein
    RAPT1
Gene names
Name: Frap1
Synonyms: Raft1
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length2549 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Kinase subunit of both mTORC1 and mTORC2, which regulate cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino-acids. Amino-acid-signaling to mTORC1 is mediated by Rag GTPases, which cause amino-acid-induced relocalization of mTOR within the endomembrane system. Growth factor-stimulated mTORC1 activation involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. 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-421', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-421'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657' By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Kinase activity is positively regulated by RHEB and negatively regulated by DEPDC6 By similarity.

Subunit structure

Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains FRAP1, MLST8, RPTOR and AKT1S1 By similarity. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains FRAP1, MLST8, PROTOR1, RICTOR and MAPKAP1 By similarity. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to PROTOR1 and RICTOR within the mTORC2 complex By similarity. Interacts with UBQLN1 By similarity. Interacts with DEPDC6 By similarity.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side By similarity.

Post-translational modification

Autophosphorylated; when part of mTORC1 or mTORC2 By similarity.

Sequence similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 FAT domain.

Contains 1 FATC domain.

Contains 7 HEAT repeats.

Contains 1 PI3K/PI4K domain.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
Mitochondrion
Mitochondrion outer membrane
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termDirect protein sequencing
Gene Ontology (GO)
   Biological processG1/S transition of mitotic cell cycle Ref.1

Traceable author statement. Source: RGD

cell projection organization

Inferred from genetic interaction. Source: MGI

negative regulation of cell size

Inferred from mutant phenotype. Source: MGI

positive regulation of endothelial cell proliferation

Inferred from mutant phenotype. Source: RGD

positive regulation of protein kinase B signaling cascade

Inferred from mutant phenotype. Source: RGD

positive regulation of translation

Inferred from mutant phenotype. Source: RGD

protein amino acid autophosphorylation

Inferred from mutant phenotype. Source: RGD

regulation of carbohydrate utilization

Inferred from direct assay. Source: RGD

regulation of fatty acid beta-oxidation

Inferred from direct assay. Source: RGD

regulation of glycogen biosynthetic process

Inferred from direct assay. Source: RGD

regulation of response to food

Inferred from direct assay. Source: RGD

   Cellular componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-KW

TORC1 complex

Inferred from mutant phenotype. Source: RGD

TORC2 complex

Inferred from mutant phenotype. Source: RGD

cytosol

Inferred from direct assay. Source: RGD

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-KW

internal side of plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from mutant phenotype. Source: RGD

soluble fraction

Inferred from direct assay. Source: RGD

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

drug binding Ref.1

Inferred from physical interaction. Source: RGD

protein binding Ref.1

Inferred from physical interaction. Source: IntAct

protein serine/threonine kinase activity

Inferred from direct assay. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DEPDC6Q8TB451EBI-1571489,EBI-2359040From a different organism.
TELO2Q9Y4R81EBI-1571489,EBI-1043674From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 25492549Serine/threonine-protein kinase mTOR
PRO_0000088810

Regions

Repeat16 – 5338HEAT 1
Repeat650 – 68839HEAT 2
Repeat859 – 89739HEAT 3
Repeat988 – 102538HEAT 4
Repeat1069 – 110638HEAT 5
Repeat1109 – 114840HEAT 6
Repeat1150 – 118637HEAT 7
Domain1382 – 1982601FAT
Domain2182 – 2516335PI3K/PI4K
Domain2517 – 254933FATC

Amino acid modifications

Modified residue5671Phosphoserine By similarity
Modified residue11621Phosphothreonine By similarity
Modified residue12181N6-acetyllysine By similarity
Modified residue12611Phosphoserine By similarity
Modified residue24781Phosphoserine By similarity
Modified residue24811Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P42346-1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: BE841EA7B9086F99

FASTA2,549288,794
        10         20         30         40         50         60 
MLGTGPATAT AGAATSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES 

        70         80         90        100        110        120 
TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN STRIGRFANY LRNLLPSSDP 

       130        140        150        160        170        180 
VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP 

       190        200        210        220        230        240 
TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE 

       250        260        270        280        290        300 
AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC 

       310        320        330        340        350        360 
KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGASPS PTKSTLVESR 

       370        380        390        400        410        420 
CCRDLMEEKF DQVCQWVLKC RSSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV 

       430        440        450        460        470        480 
LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKTVQVDA 

       490        500        510        520        530        540 
TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL 

       550        560        570        580        590        600 
KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVA SITLALRTLG SFEFEGHSLT 

       610        620        630        640        650        660 
QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL 

       670        680        690        700        710        720 
VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS 

       730        740        750        760        770        780 
MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI 

       790        800        810        820        830        840 
LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FVIIMDMLQD SSLLAKRQVA 

       850        860        870        880        890        900 
LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK 

       910        920        930        940        950        960 
VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR 

       970        980        990       1000       1010       1020 
DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV 

      1030       1040       1050       1060       1070       1080 
SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR 

      1090       1100       1110       1120       1130       1140 
VFMHDNSQGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEVPLP SRKAALETVD 

      1150       1160       1170       1180       1190       1200 
RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV 

      1210       1220       1230       1240       1250       1260 
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSS QGDALASGPV ETGPMKKLHV 

      1270       1280       1290       1300       1310       1320 
STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA 

      1330       1340       1350       1360       1370       1380 
AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI 

      1390       1400       1410       1420       1430       1440 
VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAS GVLEYAMKHF 

      1450       1460       1470       1480       1490       1500 
GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK 

      1510       1520       1530       1540       1550       1560 
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA 

      1570       1580       1590       1600       1610       1620 
QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW 

      1630       1640       1650       1660       1670       1680 
ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD 

      1690       1700       1710       1720       1730       1740 
PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK 

      1750       1760       1770       1780       1790       1800 
QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA 

      1810       1820       1830       1840       1850       1860 
VLHYKHQNQA RDEKKKLRHA SGANITNATT TATTAASAAA ATSTEGSNSE SEAESNESSP 

      1870       1880       1890       1900       1910       1920 
TPSPLQKKVT EDLSKTLLLY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN 

      1930       1940       1950       1960       1970       1980 
EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS 

      1990       2000       2010       2020       2030       2040 
KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG 

      2050       2060       2070       2080       2090       2100 
ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA 

      2110       2120       2130       2140       2150       2160 
WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL 

      2170       2180       2190       2200       2210       2220 
QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL 

      2230       2240       2250       2260       2270       2280 
SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL 

      2290       2300       2310       2320       2330       2340 
MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH 

      2350       2360       2370       2380       2390       2400 
PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRTTC 

      2410       2420       2430       2440       2450       2460 
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNAKGNK RSRTRTDSYS AGQSVEILDG 

      2470       2480       2490       2500       2510       2520 
VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD 

      2530       2540 
VPTQVELLIK QATSHENLCQ CYIGWCPFW 

« Hide

References

[1]"Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells."
Sabers C.J., Martin M.M., Brunn G.J., Williams J.M., Dumont F.J., Wiederrecht G., Abraham R.T.
J. Biol. Chem. 270:815-822(1995) [PubMed: 7822316] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs."
Sabatini D.M., Erdjument-Bromage H., Lui M., Tempst P., Snyder S.H.
Cell 78:35-43(1994) [PubMed: 7518356] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]Lubec G., Kang S.U., Lubec S.
Submitted (SEP-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 215-226 AND 533-541, MASS SPECTROMETRY.
Strain: Sprague-Dawley.
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

L37085 mRNA. Translation: AAA65929.1.
U11681 mRNA. Translation: AAA20091.1.
IPIIPI00339164.
PIRA54837.
RefSeqNP_063971.1.
UniGeneRn.11008

3D structure databases

HSSPHSSP built from PDB template 1FAP based on UniProtKB P42345.
SMRP42346. Positions 2015-2114.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:261N.
IntActP42346. 3 interactions.
STRINGP42346.

PTM databases

PhosphoSiteP42346.

Proteomic databases

PRIDEP42346.

Genome annotation databases

EnsemblENSRNOT00000014167; ENSRNOP00000014167; ENSRNOG00000009615; Rattus norvegicus. [Genome view]
GeneID56718.
KEGGrno:56718.
UCSCNM_019906. rat.

Organism-specific databases

CTD56718.
RGD68371. Frap1.

Phylogenomic databases

HOVERGENP42346.

Gene expression databases

ArrayExpressP42346.
GenevestigatorP42346.

Family and domain databases

InterProIPR011989. ARM-like.
IPR003152. FATC.
IPR009076. FKBP_rapamycin-assoc_FKBP12-bd.
IPR000403. PI3/4_kinase_cat.
IPR018936. PI3/4_kinase_CS.
IPR003151. PIK-rel_kinase_FAT.
IPR014009. PIK_FAT.
[Graphical view]
Gene3DG3DSA:1.25.10.10. ARM-like. 1 hit.
G3DSA:1.20.120.150. FRAP_FKBP12_bd. 1 hit.
G3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit.
PfamPF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF08771. Rapamycin_bind. 1 hit.
[Graphical view]
SMARTSM00146. PI3Kc. 1 hit.
[Graphical view]
PROSITEPS51189. FAT. 1 hit.
PS51190. FATC. 1 hit.
PS50077. HEAT_REPEAT. False negative.
PS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio611130.

Entry information

Entry nameFRAP_RAT
AccessionPrimary (citable) accession number: P42346
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 3, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents