Reviewed, UniProtKB/Swiss-Prot P42346 (FRAP_RAT)

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	2549 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 component	Endoplasmic reticulum Golgi apparatus Membrane Mitochondrion Mitochondrion outer membrane
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	G1/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 component	Golgi 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 function	ATP 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
DEPDC6	Q8TB45	1	EBI-1571489,EBI-2359040	From a different organism.
TELO2	Q9Y4R8	1	EBI-1571489,EBI-1043674	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2549	2549	Serine/threonine-protein kinase mTOR		PRO_0000088810
Regions
	Repeat	16 – 53	38	HEAT 1
	Repeat	650 – 688	39	HEAT 2
	Repeat	859 – 897	39	HEAT 3
	Repeat	988 – 1025	38	HEAT 4
	Repeat	1069 – 1106	38	HEAT 5
	Repeat	1109 – 1148	40	HEAT 6
	Repeat	1150 – 1186	37	HEAT 7
	Domain	1382 – 1982	601	FAT
	Domain	2182 – 2516	335	PI3K/PI4K
	Domain	2517 – 2549	33	FATC
Amino acid modifications
	Modified residue	567	1	Phosphoserine By similarity
	Modified residue	1162	1	Phosphothreonine By similarity
	Modified residue	1218	1	N6-acetyllysine By similarity
	Modified residue	1261	1	Phosphoserine By similarity
	Modified residue	2478	1	Phosphoserine By similarity
	Modified residue	2481	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P42346-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: BE841EA7B9086F99	FASTA	2,549	288,794
	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

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
EMBLGenBankDDBJ	L37085 mRNA. Translation: AAA65929.1. U11681 mRNA. Translation: AAA20091.1.
IPI	IPI00339164.
PIR	A54837.
RefSeq	NP_063971.1.
UniGene	Rn.11008
3D structure databases
HSSP	HSSP built from PDB template 1FAP based on UniProtKB P42345.
SMR	P42346. Positions 2015-2114.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:261N.
IntAct	P42346. 3 interactions.
STRING	P42346.
PTM databases
PhosphoSite	P42346.
Proteomic databases
PRIDE	P42346.
Genome annotation databases
Ensembl	ENSRNOT00000014167; ENSRNOP00000014167; ENSRNOG00000009615; Rattus norvegicus. [Genome view]
GeneID	56718.
KEGG	rno:56718.
UCSC	NM_019906. rat.
Organism-specific databases
CTD	56718.
RGD	68371. Frap1.
Phylogenomic databases
HOVERGEN	P42346.
Gene expression databases
ArrayExpress	P42346.
Genevestigator	P42346.
Family and domain databases
InterPro	IPR011989. 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]
Gene3D	G3DSA: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.
Pfam	PF02259. FAT. 1 hit. PF02260. FATC. 1 hit. PF00454. PI3_PI4_kinase. 1 hit. PF08771. Rapamycin_bind. 1 hit. [Graphical view]
SMART	SM00146. PI3Kc. 1 hit. [Graphical view]
PROSITE	PS51189. 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]
ProtoNet	Search...
Other Resources
NextBio	611130.

Entry information

Entry name

FRAP_RAT

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)