P42345

PTMD Annotation Information


※ Protein Information

Tag Content
UniProt Accession MTOR_HUMAN; P42345;
Entrez ID 2475
GenBank Protein ID NM_004958.3; XM_005263438.2;
GenBank Nucleotide ID NP_004949.1; XP_005263495.1;
Protein Name Serine/threonine-protein kinase mTOR (EC 2.7.11.1) (FK506-binding protein 12-rapamycin complex-associated protein 1) (FKBP12-rapamycin complex-associated protein) (Mammalian target of rapamycin) (mTOR) (Mechanistic target of rapamycin) (Rapamycin and FKBP
Gene Name MTOR; FRAP; FRAP1; FRAP2; RAFT1; RAPT1
Organism Homo sapiens
NCBI Taxa ID 9606
Functional DescriptionSerine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of(view all)
Sequence
(Fasta)
MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES 60
TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP 120
VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP 180
TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE 240
AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC 300
KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS PAKSTLVESR 360
CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV 420
LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA 480
TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL 540
KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT 600
QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL 660
VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS 720
MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI 780
LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA 840
LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK 900
VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR 960
DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV 1020
SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR 1080
VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD 1140
RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV 1200
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV ETGPMKKLHV 1260
STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA 1320
AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI 1380
VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF 1440
GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK 1500
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA 1560
QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW 1620
ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD 1680
PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK 1740
QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA 1800
VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE SEAESTENSP 1860
TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN 1920
EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS 1980
KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG 2040
ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA 2100
WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL 2160
QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL 2220
SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL 2280
MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH 2340
PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC 2400
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG 2460
VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD 2520
VPTQVELLIK QATSHENLCQ CYIGWCPFW

※ PTM-Disease Association

NumPTMDiseaseCell TypeTypePTM SitePMID
1PhosphorylationAmeloblastomaP22977662
[Reference]: he nuclear expression of p-mTOR, p-4E-BP1 and p-p70S6K was associated with biological behaviors (invasiveness) of ABs, and p-mTOR was an independent predictor of AB
2PhosphorylationSynovial sarcomaP23861137
[Reference]: In this study, the Akt/mTOR pathway was activated and was associated with worse clinical and pathologic behavior in patients with synovial sarcoma
3PhosphorylationPancreatic cancer/carcinoma/adenocarcinomaPaCa-2 cell lineP22726648
[Reference]: Inhibition of mTOR phosphorylation canceled gemcitabine resistance in GEM-MIA PaCa-2 cells
4PhosphorylationOesophageal adenocarcinomatumor tissueP23162107
[Reference]: Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma: a tissue microarray study
5PhosphorylationOesophageal squamous cell carcinoma/Oesophageal adenocarcinomaP22333597
[Reference]: The high percentage of p-mTOR-positive tumours supports the crucial role of mTOR activation in the pathogenesis of OSCC
6PhosphorylationEsophageal squamous cell carcinomatumor tissueU23291985; 22944293
[Reference]: Here, we show that both high levels of phosphorylated-mTOR and an increased ratio of phosphorylated-mTOR/mTOR (ratio 0.2) were significantly associated with shortened disease-specific survival in 165 patients with esophageal squamous cell carcinoma in univariate analysi
7PhosphorylationBreast cancer/tumor/carcinomaU23794518
[Reference]: Lapatinib increased the phosphorylation of AMPK at Thr172 with time- and dose-dependent manner
8PhosphorylationProstate cancer/carcinoma/adenocarcinomaU24062605
[Reference]: Our results confirmed that the phosphorylation of mTOR was over-expressed in the prostate cancer cell lines compared to RWPE-1 cells
9PhosphorylationGastric cancerU24030871
[Reference]: Phosphorylated mTOR and phosphorylated 4E-BP1 were expressed in 71.1% and 68.4% of the human GC tissues tested, respectively; significantly higher than the levels in para-cancerous tissues (50% and 57.9%) and normal tissues (44.6% and 29%).
10PhosphorylationNon-small cell lung cancer/carcinomaU23886172
[Reference]: The expression level of p-mTOR and p-RPS6KB1 was significantly higher in NSCLC tumor specimens than that in adjacent noncancerous normal lung tissues (P<0.01)
11PhosphorylationChronic myelogenous leukemia/Chronic myeloid leukemiatumor tissueU23384908
[Reference]: The phosphorylation of mTOR, 4E-BP1 and p70S6K were significantly increased in CML bone marrow cells compared with that of normal control (70.6% vs 30.0%, 76.5% vs 40.0%, 73.5% vs 20.0%, respectively, P < 0.05)
12Serine PhosphorylationProstate cancer/carcinoma/adenocarcinomatumor tissueAS244822886792
[Reference]: Moderate and strong staining was found in 36 and 11% of tumors. Loss of p(Ser2448)-mTOR staining was significantly linked to advanced stage (p = 0.0027), high-grade (p = 0.0045), nodal positive cancers (p = 0.0483), early tumor recurrence (p < 0.0001, independently from stage and grade, p = 0.0016)
13Serine PhosphorylationLiver cancercell linePS244823537100
[Reference]: CCI-779 inhibited the phosphorylation of mTOR (Ser2448), p70S6K (Thr389), S6 (Ser240/244), and 4EBP1 (Thr37/46) in different grades and the expressions of p70S6K, S6, and 4EBP1. As a result, CCI-779 induced a dose-dependent decrease in cell proliferation, G1/S arrest and damage of cell shape
14Serine PhosphorylationPancreatic cancer/carcinoma/adenocarcinomaUS244821474066
[Reference]: Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis.
15Serine PhosphorylationCervical squamous cell cancerUS244819079619
[Reference]: In conclusion, morphoproteomic analysis reveals constitutive activation and overexpression of the mTOR pathway in HSIL and SCC as evidenced by: increased nuclear translocation of pmTOR and p-p70S6K, phosphorylated at putative sites of activation, Ser2448 and Thr389, respectively
16Serine PhosphorylationAdrenocortical carcinomaUS244820484036
[Reference]: In these cells, the active Ser(2448)-phosphorylated form of mTOR is present only in mitotic cells in association with the mitotic spindle and midbody in the G(2)-M phases of the cell cycle.?
17Serine PhosphorylationBreast cancer/tumor/carcinomaUS248119956839
[Reference]: mTOR S2481 phosphorylation is useful to determine mitotic activity index (MAI), as a proliferation-associated prognostic factor for breast cancer patients.

※ Disease Cross-ref Annotation

DatabaseAnnotation
Cancer Gene Census
endometrial carcinoma, head and neck, clear cell renal cell carcinoma, anaplastic thyroid cancer, urothelial cell carcinoma, central nervous system tumours, testicular germ cell tumours and other tumour types
CTD (Curated)
(count: 15)
(view all)
MESH:D000230 ; Adenocarcinoma
MESH:D006528 ; Carcinoma, Hepatocellular
MESH:D002292 ; Carcinoma, Renal Cell
MESH:D018288 ; Carcinoma, Small Cell
MESH:C537067 ; Focal cortical dysplasia of Taylor
MESH:D006973 ; Hypertension
DisGeNet (Curated)
(count: 19)
(view all)
C0001418; Adenocarcinoma
C0007134; Renal Cell Carcinoma
C0007873; Uterine Cervical Neoplasm
C0020538; Hypertensive disease
C0025500; Mesothelioma
C0036341; Schizophrenia
GWASdb
(count: 5)
rs12139042; Corneal curvature; corneal disease
rs17036350; Corneal curvature; corneal disease
rs2300095; Obesity; obesity
rs74225573; Corneal curvature; corneal disease
rs12124983; Type 2 diabetes; type 2 diabetes mellitus

※ PTM Sites

PTM Modification Sites
Phosphorylation
(count: 74)
(view all)
102       GVEGGNATRIGRFAN     dbPAF
110       RIGRFANYLRNLLPS     dbPAF
1131      APEAPLPSRKAALET     dbPAF
1162      IIHPIVRTLDQSPEL     dbPAF
1166      IVRTLDQSPELRSTA     dbPAF
1171      DQSPELRSTAMDTLS     dbPAF
Acetylation
(count: 4)
1218      VLICRIVKGYTLADE     PLMD
1256      PVETGPMKKLHVSTI     PLMD
230       REPKEMQKPQWYRHT     PLMD
309       DLMGFGTKPRHITPF     PLMD
Ubiquitination
(count: 45)
(view all)
1133      EAPLPSRKAALETVD     PLMD
1186      SLVFQLGKKYQIFIP     PLMD
1187      LVFQLGKKYQIFIPM     PLMD
1197      IFIPMVNKVLVRHRI     PLMD
1218      VLICRIVKGYTLADE     PLMD
1256      PVETGPMKKLHVSTI     PLMD
Malonylation
(count: 4)
1218      VLICRIVKGYTLADE     PLMD
2066      ERGPQTLKETSFNQA     PLMD
230       REPKEMQKPQWYRHT     PLMD
309       DLMGFGTKPRHITPF     PLMD

※ Protein-Protein Interaction

NetworkInteraction
ABSource
B1AHF6P42345IntAct
B3KSH1P42345HPRD; MINT
O14746P42345HPRD
O14939P42345HPRD
O15530P42345HPRD; MINT
O43156P42345IntAct
P04637P42345MINT
P06730P42345IntAct
P18124P42345IntAct
P20071P42345DIP
P23443P42345HPRD
P27348P42345HPRD
P30622P42345HPRD
P31749P42345HPRD; MINT
P35568P42345HPRD
P40763P42345HPRD
P42345P42345HPRD; MINT
P42345P49841MINT
P42345P55884IntAct
P42345P61254IntAct
P42345P62249IntAct
P42345P62750MINT
P42345P62829MINT
P42345P62942HPRD; IntAct
P42345P63104MINT
P42345P63244IntAct
P42345P85299IntAct
P42345Q07817DIP
P42345Q09161IntAct
P42345Q12933IntAct; MINT
P42345Q13131HPRD
P42345Q13541HPRD; IntAct; MINT
P42345Q15019MINT
P42345Q15208MINT
P42345Q15382HPRD; DIP; MINT
P42345Q15418HPRD
P42345Q16543MINT
P42345Q6MZQ0IntAct
P42345Q6R327HPRD; IntAct;MINT
P42345Q70Z35IntAct
P42345Q8N122HPRD; DIP; IntAct; MINT
P42345Q8TAI7HPRD; MINT
P42345Q8TB45IntAct
P42345Q8TCU6IntAct
P42345Q8VBV4MINT
P42345Q8WUA4DIP
P42345Q96B36HPRD; IntAct
P42345Q96EB6IntAct
P42345Q9BPX7MINT
P42345Q9BPZ7IntAct; MINT
P42345Q9BVC4HPRD; IntAct
P42345Q9H063DIP
P42345Q9NQX3HPRD
P42345Q9UBS0HPRD
P42345Q9UMX0HPRD
P42345Q9Y265IntAct
P42345Q9Y4R8IntAct
P42345Q9Y5Q8DIP