Reviewed, UniProtKB/Swiss-Prot P42345 (FRAP_HUMAN)

Names and origin

Protein names

Recommended name:
    FKBP12-rapamycin complex-associated protein
Alternative name(s):
    FK506-binding protein 12-rapamycin complex-associated protein 1
    Rapamycin target protein
    RAPT1
    Mammalian target of rapamycin
      Short name=mTOR

Gene names

Name:	FRAP1
Synonyms:	FRAP, FRAP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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	Acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Part of the TORC2 complex which plays a critical role in AKT1 Ser-473 phosphorylation, and may modulate the phosphorylation of PKCA and regulate actin cytoskeleton organization.
Subunit structure	Interacts with the FKBP12-rapamycin complex. Binds UBQLN1. Forms part of the mammalian target of rapamycin 2 complex (TORC2) comprised of FRAP1, GBL, PRR5, RICTOR and SIN. TORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to PRR5 and RICTOR within the TORC2 complex.
Tissue specificity	Expressed in numerous tissues, with highest levels in testis.
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.
Sequence caution	The sequence AAC39933.1 differs from that shown. Reason: Frameshift at positions 956 and 999.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell growth Ref.7 Traceable author statement. Source: UniProtKB phosphorylation Ref.7 Inferred from direct assay. Source: UniProtKB protein catabolic process Ref.7 Traceable author statement. Source: UniProtKB response to nutrient Non-traceable author statement. Source: UniProtKB signal transduction Non-traceable author statement. Source: UniProtKB
Cellular component	membrane Ref.7 Inferred from direct assay. Source: UniProtKB phosphoinositide 3-kinase complex Non-traceable author statement. Source: UniProtKB
Molecular function	phosphoprotein binding Ref.7 Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.9 Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FKBP1A	P62942	1	EBI-359260,EBI-1027571
RICTOR	Q6R327	1	EBI-359260,EBI-1387196

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2549

2549

FKBP12-rapamycin complex-associated protein

PRO_0000088808

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

1162

1

Phosphothreonine

Modified residue

2478

1

Phosphoserine

Modified residue

2481

1

Phosphoserine

Natural variations

Natural variant

8

1

A → S in a lung large cell carcinoma sample; somatic mutation.

VAR_041537

Natural variant

135

1

M → T in a metastatic melanoma sample; somatic mutation.

VAR_041538

Natural variant

1083

1

M → V

VAR_041539

Natural variant

1134

1

A → V

VAR_041540

Natural variant

1178

1

S → F

VAR_041541

Natural variant

2011

1

M → V in an ovarian mucinous carcinoma sample; somatic mutation.

VAR_041542

Natural variant

2215

1

S → Y in a colorectal adenocarcinoma sample; somatic mutation.

VAR_041543

Natural variant

2476

1

P → L in a glioblastoma multiforme sample; somatic mutation.

VAR_041544

Experimental info

Sequence conflict

353

1

K → N in AAC39933. Ref.2

Sequence conflict

359

1

S → N in AAC39933. Ref.2

Sequence conflict

364

1

D → N in AAC39933. Ref.2

Sequence conflict

390

1

M → L in AAC39933. Ref.2

Sequence conflict

430

1

R → L in AAC39933. Ref.2

Sequence conflict

455 – 457

3

VLD → GVE in AAC39933. Ref.2

Sequence conflict

461

1

A → G in AAC39933. Ref.2

Sequence conflict

482 – 484

3

VFT → FFN in AAC39933. Ref.2

Sequence conflict

489

1

L → V in AAC39933. Ref.2

Sequence conflict

513

1

L → I in AAC39933. Ref.2

Sequence conflict

539

1

L → V in AAC39933. Ref.2

Sequence conflict

553

1

R → C in AAC39933. Ref.2

Sequence conflict

1075

1

I → S in AAC39933. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

2549

Helix Strand Turn

Details...

Helix

2023 – 2039

17

Helix

2044 – 2059

16

Helix

2065 – 2091

27

Helix

2095 – 2110

16

Sequences

	Sequence		Length	Mass (Da)
	P42345-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 7D9AD6E784882AB4	FASTA	2,549	288,892
	10 20 30 40 50 60 MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES 70 80 90 100 110 120 TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP 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 GLMGFGTSPS PAKSTLVESR 370 380 390 400 410 420 CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV 430 440 450 460 470 480 LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA 490 500 510 520 530 540 TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL 550 560 570 580 590 600 KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG 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 FIIIMDMLQD 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 VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD 1150 1160 1170 1180 1190 1200 RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV 1210 1220 1230 1240 1250 1260 RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG 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 NKLQQPEAAA 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 AATTAATATT TASTEGSNSE SEAESTENSP 1870 1880 1890 1900 1910 1920 TPSPLQKKVT EDLSKTLLMY 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 GLDGNYRITC 2410 2420 2430 2440 2450 2460 HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG 2470 2480 2490 2500 2510 2520 VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD 2530 2540 VPTQVELLIK QATSHENLCQ CYIGWCPFW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A mammalian protein targeted by G1-arresting rapamycin-receptor complex." Brown E.J., Albers M.W., Shin T.B., Ichikawa K., Keith C.T., Lane W.S., Schreiber S.L. Nature 369:756-758(1994) [PubMed: 8008069] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Molecular cloning and expression analysis of five novel genes in chromosome 1p36." Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A. Genomics 50:187-198(1998) [PubMed: 9653645] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[5]	"The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, is part of a tightly linked gene cluster on chromosome 1p36.2-3." Stover C., Endo Y., Takahashi M., Lynch N., Constantinescu C., Vorup-Jensen T., Thiel S., Friedl H., Hankeln T., Hall R., Gregory S., Fujita T., Schwaeble W. Genes Immun. 2:119-127(2001) [PubMed: 11426320] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1362-2549.
[6]	"RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex." Chiu M.I., Katz H., Berlin V. Proc. Natl. Acad. Sci. U.S.A. 91:12574-12578(1994) [PubMed: 7809080] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2146, TISSUE SPECIFICITY. Tissue: B-cell.
[7]	"Characterization of ubiquilin 1, an mTOR-interacting protein." Wu S., Mikhailov A., Kallo-Hosein H., Hara K., Yonezawa K., Avruch J. Biochim. Biophys. Acta 1542:41-56(2002) [PubMed: 11853878] [Abstract] Cited for: INTERACTION WITH UBQLN1.
[8]	"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton." Sarbassov D.D., Ali S.M., Kim D.-H., Guertin D.A., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M. Curr. Biol. 14:1296-1302(2004) [PubMed: 15268862] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN TORC2 COMPLEX, INTERACTION WITH RICTOR.
[9]	"Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex." Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Science 307:1098-1101(2005) [PubMed: 15718470] [Abstract] Cited for: FUNCTION.
[10]	"PRR5, a novel component of mTOR complex 2, regulates platelet-derived growth factor receptor beta expression and signaling." Woo S.-Y., Kim D.-H., Jun C.-B., Kim Y.-M., Haar E.V., Lee S.-I., Hegg J.W., Bandhakavi S., Griffin T.J., Kim D.-H. J. Biol. Chem. 282:25604-25612(2007) [PubMed: 17599906] [Abstract] Cited for: IDENTIFICATION IN TORC2 COMPLEX, INTERACTION WITH PRR5.
[11]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1162, MASS SPECTROMETRY.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2478 AND SER-2481, MASS SPECTROMETRY.
[13]	"Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP." Choi J., Chen J., Schreiber S.L., Clardy J. Science 273:239-242(1996) [PubMed: 8662507] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2018-2112.
[14]	"Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution." Liang J., Choi J., Clardy J. Acta Crystallogr. D 55:736-744(1999) [PubMed: 10089303] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2018-2112.
[15]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-8; THR-135; VAL-1083; VAL-1134; PHE-1178; VAL-2011; TYR-2215 AND LEU-2476.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L34075 mRNA. Translation: AAA58486.1. U88966 mRNA. Translation: