dbPTM

MTOR_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MTOR_MOUSE
UniProt AC	Q9JLN9
Protein Name	Serine/threonine-protein kinase mTOR
Gene Name	Mtor
Organism	Mus musculus (Mouse).
Sequence Length	2549
Subcellular Localization	Endoplasmic reticulum membrane Peripheral membrane protein Cytoplasmic side . Golgi apparatus membrane Peripheral membrane protein Cytoplasmic side . Mitochondrion outer membrane Peripheral membrane protein Cytoplasmic side . Lysosome . Cytopl
Protein Description	Serine/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 EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. [PubMed: 19440205]
Protein Sequence	MLGTGPAVATASAATSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNSTRIGRFANYLRNLLPSSDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQPNALVGLLGYSSPQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRSSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKTVQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVASITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSQGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEVPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSSQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAASGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKEDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTAHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAASAAAATSTEGSNSESEAESNENSPTPSPLQKKVTEDLSKTLLLYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRTTCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKAGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MLGTGPAV -------CCCCCCCC	35.87	-
117	Phosphorylation	YLRNLLPSSDPVVME HHHHHCCCCCHHHHH	47.55	24723360
230	Malonylation	REPKEMQKPQWYRHT CCCHHHCCCHHHHHH	37.55	26320211
230	Ubiquitination	REPKEMQKPQWYRHT CCCHHHCCCHHHHHH	37.55	-
243	Ubiquitination	HTFEEAEKGFDETLA HHHHHHHHCCCHHHH	72.44	22790023
298	Ubiquitination	QQQLVHDKYCKDLMG HHHHHCHHHHHHHCC	37.36	22790023
484	Phosphorylation	QVDATVFTCISMLAR CCCHHHHHHHHHHHH	12.47	28059163
487	Phosphorylation	ATVFTCISMLARAMG HHHHHHHHHHHHHHC	15.19	28059163
498	Ubiquitination	RAMGPGIQQDIKELL HHHCCCHHHHHHHHH	40.59	27667366
536	Ubiquitination	PQLKKDIQDGLLKML HHHHHHHHHHHHHHH	49.18	27667366
567	Phosphorylation	GLAHQLASPGLTTLP CHHHHHCCCCCCCCC	28.26	26745281
571	Phosphorylation	QLASPGLTTLPEASD HHCCCCCCCCCCHHH	32.00	26643407
572	Phosphorylation	LASPGLTTLPEASDV HCCCCCCCCCCHHHH	45.41	26643407
809	Phosphorylation	IGELAQVSGLEMRKW HHHHHHHCCCCHHHH	26.11	23737553
858	Phosphorylation	TGYVVEPYRKYPTLL CCCCCCCHHHCHHHH	13.26	21454597
861	Phosphorylation	VVEPYRKYPTLLEVL CCCCHHHCHHHHHHH	7.76	-
880	Phosphorylation	KTEQNQGTRREAIRV HHHCCCCCHHHHHHH	19.45	-
898	Ubiquitination	LGALDPYKHKVNIGM HHHCCCCCCCCCEEC	42.19	22790023
900	Ubiquitination	ALDPYKHKVNIGMID HCCCCCCCCCEECCC	32.59	22790023
1162	Phosphorylation	IIHPIVRTLDQSPEL HHHHHHHCCCCCHHH	24.64	29895711
1166	Phosphorylation	IVRTLDQSPELRSTA HHHCCCCCHHHHHHH	21.73	29895711
1218	Acetylation	VLICRIVKGYTLADE EEEEEEECCCCCCCC	43.77	23806337
1218	Ubiquitination	VLICRIVKGYTLADE EEEEEEECCCCCCCC	43.77	27667366
1218	Malonylation	VLICRIVKGYTLADE EEEEEEECCCCCCCC	43.77	26320211
1239	Phosphorylation	YQHRMLRSSQGDALA HHHHHHHHCCCCHHH	24.05	29472430
1240	Phosphorylation	QHRMLRSSQGDALAS HHHHHHHCCCCHHHC	31.58	29472430
1247	Phosphorylation	SQGDALASGPVETGP CCCCHHHCCCCCCCC	44.47	29472430
1256	Ubiquitination	PVETGPMKKLHVSTI CCCCCCCCEEEEEEE	56.15	22790023
1257	Ubiquitination	VETGPMKKLHVSTIN CCCCCCCEEEEEEEE	37.26	22790023
1261	Phosphorylation	PMKKLHVSTINLQKA CCCEEEEEEEEHHHH	16.90	25521595
1262	Phosphorylation	MKKLHVSTINLQKAW CCEEEEEEEEHHHHH	16.88	27818261
1293	Ubiquitination	RLSLELLKDSSSPSL HHHHHHHCCCCCHHH	69.09	22790023
1400	Ubiquitination	YAKALHYKELEFQKG HHHHHCHHHHCCCCC	45.11	22790023
1406	Ubiquitination	YKELEFQKGPTPAIL HHHHCCCCCCCHHHH	72.65	22790023
1415	Phosphorylation	PTPAILESLISINNK CCHHHHHHHHHCCCC	27.79	21743459
1418	Phosphorylation	AILESLISINNKLQQ HHHHHHHHCCCCCCC	25.26	21743459
1430	Phosphorylation	LQQPEAASGVLEYAM CCCHHHHHHHHHHHH	36.16	-
1465	Ubiquitination	DALVAYDKKMDTNKE HHHHHHHHCCCCCCC	37.00	22790023
1471	Ubiquitination	DKKMDTNKEDPELML HHCCCCCCCCHHHHH	66.63	22790023
1511	Ubiquitination	VNDETQAKMARMAAA CCHHHHHHHHHHHHH	24.23	22790023
1650	Ubiquitination	VVSPHEDMRTWLKYA CCCCCHHHHHHHHHH	3.61	27667366
1655	Ubiquitination	EDMRTWLKYASLCGK HHHHHHHHHHHHCCH	30.27	22790023
1821	Phosphorylation	KKKLRHASGANITNA HHHHHHHCCCCCCCH	32.11	25293948
1826	Phosphorylation	HASGANITNATTAAT HHCCCCCCCHHHHHH	20.71	25293948
1829	Phosphorylation	GANITNATTAATTAA CCCCCCHHHHHHHHH	21.02	25293948
1830	Phosphorylation	ANITNATTAATTAAS CCCCCHHHHHHHHHH	16.34	25293948
1833	Phosphorylation	TNATTAATTAASAAA CCHHHHHHHHHHHHH	17.95	25293948
1834	Phosphorylation	NATTAATTAASAAAA CHHHHHHHHHHHHHH	18.59	25293948
1837	Phosphorylation	TAATTAASAAAATST HHHHHHHHHHHHHCC	18.90	25293948
1842	Phosphorylation	AASAAAATSTEGSNS HHHHHHHHCCCCCCC	31.30	25293948
1843	Phosphorylation	ASAAAATSTEGSNSE HHHHHHHCCCCCCCH	21.53	25293948
1844	Phosphorylation	SAAAATSTEGSNSES HHHHHHCCCCCCCHH	39.76	25293948
1847	Phosphorylation	AATSTEGSNSESEAE HHHCCCCCCCHHHHH	30.83	19060867
1849	Phosphorylation	TSTEGSNSESEAESN HCCCCCCCHHHHHCC	44.17	25293948
1851	Phosphorylation	TEGSNSESEAESNEN CCCCCCHHHHHCCCC	41.76	19060867
1855	Phosphorylation	NSESEAESNENSPTP CCHHHHHCCCCCCCC	57.39	25293948
1859	Phosphorylation	EAESNENSPTPSPLQ HHHCCCCCCCCCHHH	24.79	25293948
1861	Phosphorylation	ESNENSPTPSPLQKK HCCCCCCCCCHHHHH	35.90	25293948
1893	Phosphorylation	QGFFRSISLSRGNNL HHHHHHHCCCCCCCH	22.87	22006019
2066	Ubiquitination	ERGPQTLKETSFNQA HHCCCCHHHCCHHHH	63.43	22790023
2069	Phosphorylation	PQTLKETSFNQAYGR CCCHHHCCHHHHHCH	24.24	23684622
2159	Phosphorylation	RIQSIAPSLQVITSK EEECCCCCCEEECCC	23.55	-
2164	Phosphorylation	APSLQVITSKQRPRK CCCCEEECCCCCCCE	30.89	-
2173	Phosphorylation	KQRPRKLTLMGSNGH CCCCCEEEEECCCCC	20.10	-
2370	Ubiquitination	EVAMTREKFPEKIPF HHHHCCCCCCCCCCH	64.03	22790023
2442	Phosphorylation	NTKGNKRSRTRTDSY CCCCCCCCCCCCCCC	39.34	22322096
2444	Phosphorylation	KGNKRSRTRTDSYSA CCCCCCCCCCCCCCC	38.88	25619855
2446	Phosphorylation	NKRSRTRTDSYSAGQ CCCCCCCCCCCCCCC	28.78	25619855
2448	Phosphorylation	RSRTRTDSYSAGQSV CCCCCCCCCCCCCCE	22.00	19643477
2449	Phosphorylation	SRTRTDSYSAGQSVE CCCCCCCCCCCCCEE	12.83	25619855
2450	Phosphorylation	RTRTDSYSAGQSVEI CCCCCCCCCCCCEEE	29.85	25619855
2454	Phosphorylation	DSYSAGQSVEILDGV CCCCCCCCEEECCCC	22.31	22322096
2473	Phosphorylation	PAHKKAGTTVPESIH CCHHHCCCCCCHHHH	29.49	26824392
2474	Phosphorylation	AHKKAGTTVPESIHS CHHHCCCCCCHHHHH	32.90	27087446
2478	Phosphorylation	AGTTVPESIHSFIGD CCCCCCHHHHHHHCC	21.38	25521595
2481	Phosphorylation	TVPESIHSFIGDGLV CCCHHHHHHHCCCCC	19.52	20138985
2496	Ubiquitination	KPEALNKKAIQIINR CHHHCCHHHHHHHHH	50.04	22790023

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
2173	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot
2446	T	Phosphorylation	Kinase	PRKAA1	Q13131	GPS
2446	T	Phosphorylation	Kinase	RPS6KB1	Q8BSK8	Uniprot
2446	T	Phosphorylation	Kinase	AMPK-FAMILY	-	GPS
2446	T	Phosphorylation	Kinase	AMPK_GROUP	-	PhosphoELM
2448	S	Phosphorylation	Kinase	RPS6KB1	Q8BSK8	Uniprot
2481	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
1261	S	Phosphorylation	19487463
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
2159	S	Phosphorylation	19487463
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
2164	T	Phosphorylation	19487463
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
2173	T	Phosphorylation	19487463
Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity (By similarity).

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of MTOR_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
FKB1A_HUMAN	FKBP1A	physical	9334222
RICTR_MOUSE	Rictor	physical	20801936
IKKA_MOUSE	Chuk	physical	22351927
LST8_HUMAN	MLST8	physical	18235224
RPTOR_HUMAN	RPTOR	physical	18235224
DDB1_HUMAN	DDB1	physical	18235224
RICTR_HUMAN	RICTOR	physical	18235224
KS6B1_MOUSE	Rps6kb1	physical	17386266
RICTR_MOUSE	Rictor	physical	18664580
RICTR_MOUSE	Rictor	physical	18851840
LST8_MOUSE	Mlst8	physical	18851840
MLXIP_MOUSE	Mlxip	physical	25332233

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MTOR_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Site-specific mTOR phosphorylation promotes mTORC1-mediated signalingand cell growth."; Acosta-Jaquez H.A., Keller J.A., Foster K.G., Ekim B., Soliman G.A.,Feener E.P., Ballif B.A., Fingar D.C.; Mol. Cell. Biol. 29:4308-4324(2009). Cited for: PHOSPHORYLATION AT SER-1261, AND ENZYME REGULATION.	19487463 [Abstract]
"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry."; Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.; J. Proteome Res. 7:5314-5326(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2481, AND MASSSPECTROMETRY.	19367708 [Abstract]
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2478 AND SER-2481, ANDMASS SPECTROMETRY.	17242355 [Abstract]

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