EKS-HOS-00094

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00094

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
Atypical/PIKK	447.2	1.9E-133	358	682	325

Status

Reviewed

Ensembl Protein

ENSP00000366034

UniProt Accession

P42345; Q4LE76; Q5TER1; Q6LE87; Q96QG3; Q9Y4I3;

Protein Name

Serine/threonine-protein kinase mTOR

Protein Synonyms/Alias

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 FKBP12 target 1; Rapamycin target protein 1;

Gene Name

MTOR

Gene Synonyms/Alias

MTOR; FRAP, FRAP1, FRAP2, RAFT1, RAPT1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000198793	ENSP00000398745	ENST00000455339
ENSG00000198793	ENSP00000354558	ENST00000361445
ENSG00000198793	ENSP00000366034	ENST00000376838

Organism

Homo sapiens

Functional Description

Serine/threonine protein kinase which is a centralregulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. 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. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a 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'.

Protein Length

754

Protein Sequence
(FASTA)

MNFEAVLHYK HQNQARDEKK KLRHASGANI TNATTAATTA ATATTTASTE GSNSESEAES 60

TENSPTPSPL QKKVTEDLSK TLLMYTVPAV QGFFRSISLS RGNNLQDTLR VLTLWFDYGH 120

WPDVNEALVE GVKAIQIDTW LQVIPQLIAR IDTPRPLVGR LIHQLLTDIG RYHPQALIYP 180

LTVASKSTTT ARHNAANKIL KNMCEHSNTL VQQAMMVSEE LIRVAILWHE MWHEGLEEAS 240

RLYFGERNVK GMFEVLEPLH AMMERGPQTL KETSFNQAYG RDLMEAQEWC RKYMKSGNVK 300

DLTQAWDLYY HVFRRISKQL PQLTSLELQY VSPKLLMCRD LELAVPGTYD PNQPIIRIQS 360

IAPSLQVITS KQRPRKLTLM GSNGHEFVFL LKGHEDLRQD ERVMQLFGLV NTLLANDPTS 420

LRKNLSIQRY AVIPLSTNSG LIGWVPHCDT LHALIRDYRE KKKILLNIEH RIMLRMAPDY 480

DHLTLMQKVE VFEHAVNNTA GDDLAKLLWL KSPSSEVWFD RRTNYTRSLA VMSMVGYILG 540

LGDRHPSNLM LDRLSGKILH IDFGDCFEVA MTREKFPEKI PFRLTRMLTN AMEVTGLDGN 600

YRITCHTVME VLREHKDSVM AVLEAFVYDP LLNWRLMDTN TKGNKRSRTR TDSYSAGQSV 660

EILDGVELGE PAHKKTGTTV PESIHSFIGD GLVKPEALNK KAIQIINRVR DKLTGRDFSH 720

DDTLDVPTQV ELLIKQATSH ENLCQCYIGW CPFW 754

Nucleotide Sequence
(FASTA)

ATGAACTTCG AAGCTGTGCT ACACTACAAA CATCAGAACC AAGCCCGCGA TGAGAAGAAG 60

AAACTGCGTC ATGCCAGCGG GGCCAACATC ACCAACGCCA CCACTGCCGC CACCACGGCC 120

GCCACTGCCA CCACCACTGC CAGCACCGAG GGCAGCAACA GTGAGAGCGA GGCCGAGAGC 180

ACCGAGAACA GCCCCACCCC ATCGCCGCTG CAGAAGAAGG TCACTGAGGA TCTGTCCAAA 240

ACCCTCCTGA TGTACACGGT GCCTGCCGTC CAGGGCTTCT TCCGTTCCAT CTCCTTGTCA 300

CGAGGCAACA ACCTCCAGGA TACACTCAGA GTTCTCACCT TATGGTTTGA TTATGGTCAC 360

TGGCCAGATG TCAATGAGGC CTTAGTGGAG GGGGTGAAAG CCATCCAGAT TGATACCTGG 420

CTACAGGTTA TACCTCAGCT CATTGCAAGA ATTGATACGC CCAGACCCTT GGTGGGACGT 480

CTCATTCACC AGCTTCTCAC AGACATTGGT CGGTACCACC CCCAGGCCCT CATCTACCCA 540

CTGACAGTGG CTTCTAAGTC TACCACGACA GCCCGGCACA ATGCAGCCAA CAAGATTCTG 600

AAGAACATGT GTGAGCACAG CAACACCCTG GTCCAGCAGG CCATGATGGT GAGCGAGGAG 660

CTGATCCGAG TGGCCATCCT CTGGCATGAG ATGTGGCATG AAGGCCTGGA AGAGGCATCT 720

CGTTTGTACT TTGGGGAAAG GAACGTGAAA GGCATGTTTG AGGTGCTGGA GCCCTTGCAT 780

GCTATGATGG AACGGGGCCC CCAGACTCTG AAGGAAACAT CCTTTAATCA GGCCTATGGT 840

CGAGATTTAA TGGAGGCCCA AGAGTGGTGC AGGAAGTACA TGAAATCAGG GAATGTCAAG 900

GACCTCACCC AAGCCTGGGA CCTCTATTAT CATGTGTTCC GACGAATCTC AAAGCAGCTG 960

CCTCAGCTCA CATCCTTAGA GCTGCAATAT GTTTCCCCAA AACTTCTGAT GTGCCGGGAC 1020

CTTGAATTGG CTGTGCCAGG AACATATGAC CCCAACCAGC CAATCATTCG CATTCAGTCC 1080

ATAGCACCGT CTTTGCAAGT CATCACATCC AAGCAGAGGC CCCGGAAATT GACACTTATG 1140

GGCAGCAACG GACATGAGTT TGTTTTCCTT CTAAAAGGCC ATGAAGATCT GCGCCAGGAT 1200

GAGCGTGTGA TGCAGCTCTT CGGCCTGGTT AACACCCTTC TGGCCAATGA CCCAACATCT 1260

CTTCGGAAAA ACCTCAGCAT CCAGAGATAC GCTGTCATCC CTTTATCGAC CAACTCGGGC 1320

CTCATTGGCT GGGTTCCCCA CTGTGACACA CTGCACGCCC TCATCCGGGA CTACAGGGAG 1380

AAGAAGAAGA TCCTTCTCAA CATCGAGCAT CGCATCATGT TGCGGATGGC TCCGGACTAT 1440

GACCACTTGA CTCTGATGCA GAAGGTGGAG GTGTTTGAGC ATGCCGTCAA TAATACAGCT 1500

GGGGACGACC TGGCCAAGCT GCTGTGGCTG AAAAGCCCCA GCTCCGAGGT GTGGTTTGAC 1560

CGAAGAACCA ATTATACCCG TTCTTTAGCG GTCATGTCAA TGGTTGGGTA TATTTTAGGC 1620

CTGGGAGATA GACACCCATC CAACCTGATG CTGGACCGTC TGAGTGGGAA GATCCTGCAC 1680

ATTGACTTTG GGGACTGCTT TGAGGTTGCT ATGACCCGAG AGAAGTTTCC AGAGAAGATT 1740

CCATTTAGAC TAACAAGAAT GTTGACCAAT GCTATGGAGG TTACAGGCCT GGATGGCAAC 1800

TACAGAATCA CATGCCACAC AGTGATGGAG GTGCTGCGAG AGCACAAGGA CAGTGTCATG 1860

GCCGTGCTGG AAGCCTTTGT CTATGACCCC TTGCTGAACT GGAGGCTGAT GGACACAAAT 1920

ACCAAAGGCA ACAAGCGATC CCGAACGAGG ACGGATTCCT ACTCTGCTGG CCAGTCAGTC 1980

GAAATTTTGG ACGGTGTGGA ACTTGGAGAG CCAGCCCATA AGAAAACGGG GACCACAGTG 2040

CCAGAATCTA TTCATTCTTT CATTGGAGAC GGTTTGGTGA AACCAGAGGC CCTAAATAAG 2100

AAAGCTATCC AGATTATTAA CAGGGTTCGA GATAAGCTCA CTGGTCGGGA CTTCTCTCAT 2160

GATGACACTT TGGATGTTCC AACGCAAGTT GAGCTGCTCA TCAAACAAGC GACATCCCAT 2220

GAAAACCTCT GCCAGTGCTA TATTGGCTGG TGCCCTTTCT GGTAA 2265

Domain Profile

S: 1     iagfderveilaskqkpkklllrGsdgkeypyLvkgkeDlrqdervlqlfslvNtlLakd  60

         i+++++++++++skq+p+kl+l+Gs+g+e+++L+kg+eDlrqderv+qlf+lvNtlLa+d

Q: 358   IQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLAND  417

         899*********************************************************

S: 61    ketsrrkLkirtykVvplstrsgliewventvsLkellkklvekkavlldqpisyrykdl  120

         +++ r++L+i++y+V+plst+sgli+wv+++++L++l+++++ekk++ll+        ++

Q: 418   PTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLN-------IEH  470

         *************************************************9.......9**

S: 121   stvqarkpklkhlkls..levfkevlenlvpkdllkklllekfpspeewfelrkaytrsl  178

         +++ +++p+++hl+l+  +evf+++++n ++ d l+kll+ k+ps+e+wf++r++ytrsl

Q: 471   RIMLRMAPDYDHLTLMqkVEVFEHAVNN-TAGDDLAKLLWLKSPSSEVWFDRRTNYTRSL  529

         ****************************.999****************************

S: 179   AvislvgyiLgLgdrhlenllidqetgevvhidfgvafekaktqlkvpekvPFRLTrniv  238

         Av+s+vgyiLgLgdrh++nl++d+ +g+++hidfg +fe a+t++k+pek+PFRLTr+++

Q: 530   AVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLT  589

         ************************************************************

S: 239   nalgvtgveGvfrasceavlrvlreskeklltiLevflydplvdwkkkkktsketeeela  298

         na++vtg++G++r++c++v++vlre+k++++++Le+f+ydpl++w+ +++++k+++++++

Q: 590   NAMEVTGLDGNYRITCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRT  649

         ************************************************************

S: 299   ekakaealkikkllskvekaenavatrdlllle  331

         ++++++a +++++l++ve +e+a+++++++++e

Q: 650   RTDSYSAGQSVEILDGVELGEPAHKKTGTTVPE  682

         ****************************99987

Domain Sequence
(FASTA)

IQSIAPSLQV ITSKQRPRKL TLMGSNGHEF VFLLKGHEDL RQDERVMQLF GLVNTLLAND 60

PTSLRKNLSI QRYAVIPLST NSGLIGWVPH CDTLHALIRD YREKKKILLN IEHRIMLRMA 120

PDYDHLTLMQ KVEVFEHAVN NTAGDDLAKL LWLKSPSSEV WFDRRTNYTR SLAVMSMVGY 180

ILGLGDRHPS NLMLDRLSGK ILHIDFGDCF EVAMTREKFP EKIPFRLTRM LTNAMEVTGL 240

DGNYRITCHT VMEVLREHKD SVMAVLEAFV YDPLLNWRLM DTNTKGNKRS RTRTDSYSAG 300

QSVEILDGVE LGEPAHKKTG TTVPE 325

Keyword

3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Endoplasmic reticulum; Golgi apparatus; Kinase; Lysosome; Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Rattus norvegicus"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Saccharomyces cerevisiae"; ?>Schizosaccharomyces pombe"; ?>

Gene Ontology

GO:0030425	; C:dendrite
GO:0012505	; C:endomembrane system
GO:0005789	; C:endoplasmic reticulum membrane
GO:0000139	; C:Golgi membrane
GO:0005764	; C:lysosome
GO:0016020	; C:membrane
GO:0005741	; C:mitochondrial outer membrane
GO:0070438	; C:mTOR-FKBP12-rapamycin complex
GO:0043025	; C:neuronal cell body
GO:0005942	; C:phosphatidylinositol 3-kinase complex
GO:0016605	; C:PML body
GO:0031931	; C:TORC1 complex
GO:0031932	; C:TORC2 complex
GO:0005524	; F:ATP binding
GO:0008144	; F:drug binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0043022	; F:ribosome binding
GO:0001030	; F:RNA polymerase III type 1 promoter DNA binding
GO:0001031	; F:RNA polymerase III type 2 promoter DNA binding
GO:0001032	; F:RNA polymerase III type 3 promoter DNA binding
GO:0001156	; F:TFIIIC-class transcription factor binding
GO:0016049	; P:cell growth
GO:0071456	; P:cellular response to hypoxia
GO:0031669	; P:cellular response to nutrient levels
GO:0007173	; P:epidermal growth factor receptor signaling pathway
GO:0008543	; P:fibroblast growth factor receptor signaling pathway
GO:0007281	; P:germ cell development
GO:0008286	; P:insulin receptor signaling pathway
GO:0010507	; P:negative regulation of autophagy
GO:0045792	; P:negative regulation of cell size
GO:0016242	; P:negative regulation of macroautophagy
GO:0051534	; P:negative regulation of NFAT protein import into nucleus
GO:0048011	; P:nerve growth factor receptor signaling pathway
GO:0018105	; P:peptidyl-serine phosphorylation
GO:0018107	; P:peptidyl-threonine phosphorylation
GO:0048015	; P:phosphatidylinositol-mediated signaling
GO:0030838	; P:positive regulation of actin filament polymerization
GO:0001938	; P:positive regulation of endothelial cell proliferation
GO:0010592	; P:positive regulation of lamellipodium assembly
GO:0046889	; P:positive regulation of lipid biosynthetic process
GO:0050731	; P:positive regulation of peptidyl-tyrosine phosphorylation
GO:0051897	; P:positive regulation of protein kinase B signaling cascade
GO:0001934	; P:positive regulation of protein phosphorylation
GO:0051496	; P:positive regulation of stress fiber assembly
GO:0045945	; P:positive regulation of transcription from RNA polymerase III promoter
GO:0045727	; P:positive regulation of translation
GO:0046777	; P:protein autophosphorylation
GO:0030163	; P:protein catabolic process
GO:0032956	; P:regulation of actin cytoskeleton organization
GO:0043610	; P:regulation of carbohydrate utilization
GO:0031998	; P:regulation of fatty acid beta-oxidation
GO:0005979	; P:regulation of glycogen biosynthetic process
GO:0045859	; P:regulation of protein kinase activity
GO:0032314	; P:regulation of Rac GTPase activity
GO:0032095	; P:regulation of response to food
GO:0043200	; P:response to amino acid stimulus
GO:0007584	; P:response to nutrient
GO:0031529	; P:ruffle organization
GO:0031295	; P:T cell costimulation
GO:0031929	; P:TOR signaling cascade

KEGG

hsa:2475

;

InterPros

IPR011989	; ARM-like.
IPR016024	; ARM-type_fold.
IPR024585	; DUF3385_TOR.
IPR003152	; FATC.
IPR011009	; Kinase-like_dom.
IPR000403	; PI3/4_kinase_cat_dom.
IPR018936	; PI3/4_kinase_CS.
IPR003151	; PIK-rel_kinase_FAT.
IPR014009	; PIK_FAT.
IPR009076	; Rapamycin-bd_dom.
IPR026683	; TOR/Smg1.

Pfam

PF11865	; DUF3385; 1.
PF02259	; FAT; 1.
PF02260	; FATC; 1.
PF00454	; PI3_PI4_kinase; 1.
PF08771	; Rapamycin_bind; 1.

SMARTs

SM00146

; PI3Kc; 1.

Prosites

PS51189	; FAT; 1.
PS51190	; FATC; 1.
PS50077	; HEAT_REPEAT; FALSE_NEG.
PS00915	; PI3_4_KINASE_1; 1.
PS00916	; PI3_4_KINASE_2; 1.
PS50290	; PI3_4_KINASE_3; 1.

Prints

Created Date

20-Feb-2013