dbPTM

MTOR_RAT - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MTOR_RAT
UniProt AC	P42346
Protein Name	Serine/threonine-protein kinase mTOR
Gene Name	Mtor
Organism	Rattus norvegicus (Rat).
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-421'. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity)..
Protein Sequence	MLGTGPATATAGAATSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNSTRIGRFANYLRNLLPSSDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGASPSPTKSTLVESRCCRDLMEEKFDQVCQWVLKCRSSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKTVQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVASITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFVIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSQGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEVPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSSQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAASGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTTATTAASAAAATSTEGSNSESEAESNESSPTPSPLQKKVTEDLSKTLLLYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRTTCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNAKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MLGTGPAT -------CCCCCCCC	35.87	-
230	Acetylation	REPKEMQKPQWYRHT CCCHHHCCCHHHHHH	37.55	22902405
567	Phosphorylation	GLAHQLASPGLTTLP CHHHHHCCCCCCCCC	28.26	-
809	Phosphorylation	IGELAQVSGLEMRKW HHHHHHHCCCCHHHH	26.11	22673903
947	Phosphorylation	NLPLDEFYPAVSMVA CCCHHHHHHHHHHHH	6.55	24972320
1162	Phosphorylation	IIHPIVRTLDQSPEL HHHHHHHCCCCCHHH	24.64	-
1218	Acetylation	VLICRIVKGYTLADE EEEEEEECCCCCCCC	43.77	22902405
1261	Phosphorylation	PMKKLHVSTINLQKA CCCEEEEEEEEHHHH	16.90	29779826
1262	Phosphorylation	MKKLHVSTINLQKAW CCEEEEEEEEHHHHH	16.88	27097102
1418	Phosphorylation	AILESLISINNKLQQ HHHHHHHHCCCCCCC	25.26	23984901
1656	Phosphorylation	DMRTWLKYASLCGKS HHHHHHHHHHHCCHH	10.15	-
1891	Phosphorylation	AVQGFFRSISLSRGN HHHHHHHHHCCCCCC	16.04	21630457
2159	Phosphorylation	RIQSIAPSLQVITSK EEECCCCCCEEECCC	23.55	-
2164	Phosphorylation	APSLQVITSKQRPRK CCCCEEECCCCCCCE	30.89	21576368
2173	Phosphorylation	KQRPRKLTLMGSNGH CCCCCEEEEECCCCC	20.10	-
2307	Phosphorylation	AKLLWLKSPSSEVWF HHHHHHCCCCCCCEE	28.04	30181290
2309	Phosphorylation	LLWLKSPSSEVWFDR HHHHCCCCCCCEEEC	46.34	30181290
2310	Phosphorylation	LWLKSPSSEVWFDRR HHHCCCCCCCEEECC	39.28	30181290
2444	Phosphorylation	KGNKRSRTRTDSYSA CCCCCCCCCCCCCCC	38.88	25403869
2446	Phosphorylation	NKRSRTRTDSYSAGQ CCCCCCCCCCCCCCC	28.78	23984901
2448	Phosphorylation	RSRTRTDSYSAGQSV CCCCCCCCCCCCCCE	22.00	15358595
2449	Phosphorylation	SRTRTDSYSAGQSVE CCCCCCCCCCCCCEE	12.83	23984901
2450	Phosphorylation	RTRTDSYSAGQSVEI CCCCCCCCCCCCEEE	29.85	25403869
2454	Phosphorylation	DSYSAGQSVEILDGV CCCCCCCCEEEECCC	22.31	25403869
2471	Phosphorylation	GEPAHKKTGTTVPES CCCCHHCCCCCCCHH	44.56	27097102
2473	Phosphorylation	PAHKKTGTTVPESIH CCHHCCCCCCCHHHH	29.83	27097102
2474	Phosphorylation	AHKKTGTTVPESIHS CHHCCCCCCCHHHHH	35.09	27097102
2478	Phosphorylation	TGTTVPESIHSFIGD CCCCCCHHHHHHHCC	21.38	27097102
2481	Phosphorylation	TVPESIHSFIGDGLV CCCHHHHHHHCCCCC	19.52	20138985

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	P47196	Uniprot
2446	T	Phosphorylation	Kinase	RPS6KB1	P67999	Uniprot
2448	S	Phosphorylation	Kinase	RPS6KB1	P67999	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
1261	S	Phosphorylation	-
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
2159	S	Phosphorylation	-
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
2164	T	Phosphorylation	21576368
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
2173	T	Phosphorylation	-
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_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
4EBP1_HUMAN	EIF4EBP1	physical	10364159
GEPH_HUMAN	GPHN	physical	10325225
4EBP1_RAT	Eif4ebp1	physical	10471835
4EBP1_HUMAN	EIF4EBP1	physical	9204908
4EBP1_RAT	Eif4ebp1	physical	9204908

Drug and Disease Associations

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

Regulatory Network of MTOR_RAT

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"mTOR kinase domain phosphorylation promotes mTORC1 signaling, cellgrowth, and cell cycle progression."; Ekim B., Magnuson B., Acosta-Jaquez H.A., Keller J.A., Feener E.P.,Fingar D.C.; Mol. Cell. Biol. 31:2787-2801(2011). Cited for: AUTOPHOSPHORYLATION AT THR-2164.	21576368 [Abstract]

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