CODSWALLOP

Serine/threonine-protein kinase mTOR

Homo sapiens · seed P42345 · 2549 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

102Entries 102Entities 39Constructs 6Organisms 72Ligand-bound
1.45 ÅBest res.
3.20 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

9DL0, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 9DL0
9DL0 at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

11274254993 constructs

Constructs, most-used first

39 distinct constructs across 102 entries. 67 polymer entities differ from the UniProt canonical sequence in some way, 19 carry a recognised expression tag and 0 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
16 2549 2.86 8ERA matches the canonical sequence
9 993 2.80 8JCU Strep-II; residues 1150-2045; 9 internal deletions; 18-residue insertion after 1759; T1150D, L1151Y, A1152K +611 more
7 2590 2.60 9T94 Strep-II; TEV site
6 1174 3.20 4JSN residues 1376-2549
5 94 1.85 3FAP residues 2019-2112
5 2474 2.93 9RST matches the canonical sequence
4 98 1.45 4DRI residues 2017-2114; I2017G, R2018A, V2019M +5 more
4 2368 3.80 6Z3A matches the canonical sequence
3 33 residues 2438-2470
3 92 1.90 9PIW residues 2021-2112
3 2549 3.67 7PEB matches the canonical sequence
3 2571 3.20 7PE8 FLAG
2 95 2.20 6M4U residues 2019-2113; V2019G, A2020S, T2098L
2 95 2.81 8ER6 residues 2018-2112; R2018G
2 100 2.33 1AUE residues 2015-2114
2 752 2.90 21KR residues 1378-2051; 11 internal deletions; 20-residue insertion after 1943; W1378D, E1380K, K1381D +422 more
2 1177 3.10 5WBY residues 1373-2549; P1373G, L1374T, R1375G
2 2549 3.23 6BCX matches the canonical sequence
2 2812 3.63 9IZ0 matches the canonical sequence
1 93 1.55 9DBO residues 2021-2113
1 93 1.67 5GPG residues 2020-2112; A2020S
1 95 2.70 1FAP residues 2018-2112
1 98 2.00 9DL0 residues 2020-2117; A2020S, Q2114G, L2115G +2 more
1 98 2.95 9NGT residues 2017-2114; I2017G
1 102 1.75 5WBH residues 2016-2117; L2016G, I2017S, L2115S +2 more

Showing the 25 most-used of 39.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

E1290H 39% W1304Y 39% A1309S 39% N1311E 39% M1313V 39% E1331A 39% R1339I 39% I1341G 39% T1346S 39% V1353Q 39% T1354V 39% S1239K 38% Q1241E 38% A1244L 38% T1262R 38% A1272I 38% R1273D 38% R1274E 38% V1275I 38% S1276N 38% Q1348S 38% D1349S 38% I1350V 38% A1351S 38% D1294T 38% S1327D 38% S1340A 38% L1374I 38% T1221D 37% A1223K 37%

What it assembles into

Oligomeric stateChainsEntriesShare
dimeric2 32 31.4%
octameric8 15 14.7%
tetrameric4 15 14.7%
trimeric3 11 10.8%
monomeric1 10 9.8%
dodecameric12 4 3.9%
decameric10 4 3.9%
pentameric5 3 2.9%

35 entries have the depositor's assembly corroborated by PISA, 66 carry the depositor's word alone and 0 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 1 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 5WBH.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHSCOP2B112742549
DomainSourceSpan (seed)Chains
FKBP12-rapamycin binding domainCATH 1.20.120.150 2020–2113 14
FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP)SCOP2B 8036936 2020–2112 60
Frizzled domain-likeSCOP2B 8083832 2028–2145 2

What binds it

IHP IHP24 entries RAP RAP12 entries NAG NAG12 entries ANP ANP8 entries GTP GTP6 entries Z99 Z996 entries GDP GDP5 entries ACE ACE5 entries ADP ADP4 entries ATP ATP4 entries GLU GLU4 entries AGS AGS3 entries
ComponentClassNameEntriesBest (Å)
IHPligand Inositol Hexakisphosphate 24 2.60
ZNion Zinc Ion 17 2.20
MGion Magnesium Ion 13 3.10
RAPligand Rapamycin Immunosuppressant Drug 12 1.45
NAGcofactor 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose 12 2.80
ANPcofactor Phosphoaminophosphonic Acid-Adenylate Ester 8 3.10
GTPcofactor Guanosine-5'-Triphosphate 6 3.20
Z99ligand 2-[(1s,2s)-2-Carboxycyclopropyl]-3-(9h-Xanthen-9-Yl)-D-Alanine 6 2.80
GDPcofactor Guanosine-5'-Diphosphate 5 3.20
ACEligand Acetyl Group 5 3.00
ADPcofactor Adenosine-5'-Diphosphate 4 2.60
ATPcofactor Adenosine-5'-Triphosphate 4 2.60
CLRlipid/detergent Cholesterol 4 2.90
GLUligand Glutamic Acid 4 2.80
AGScofactor Phosphothiophosphoric Acid-Adenylate Ester 3 3.00
GSPcofactor 5'-Guanosine-Diphosphate-Monothiophosphate 3 3.16
RADligand C49-Methyl Rapamycin 2 2.20
ARDligand C15-(R)-Methylthienyl Rapamycin 2 1.85
MGFligand Trifluoromagnesate 2 3.50
SO4ion Sulfate Ion 2 1.80

How it crystallises

Parsed from the free text 28 depositors typed into _exptl_crystal_grow.pdbx_details, out of 29 entries that recorded anything at all. Median pH 8.0 (range 3.5 to 8.5).

Precipitants

PEG × Sodium chloride × Ammonium sulfate × MPD × Tacsimate × Sodium formate × Isopropanol × Calcium chloride ×

Buffers

Tris × HEPES × Citrate × Sodium acetate × Bis-Tris × Sodium cacodylate × MES ×

Which entries to trust

101 entries carry a wwPDB validation report: 63 clean, 18 worth a check and 20 with something to explain. Median clashscore 5.09, median RSRZ outliers 2.66%, median R-free minus R-work 0.038. 100 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens87 1.45 67 100%
Saccharomyces cerevisiae7 2.93 3 99%
Saccharomyces cerevisiae S288C5 3.80 1 99%
Schizosaccharomyces pombe 972h-1 3.63 1 16%
Schizosaccharomyces pombe1 4.32 0 16%
Kluyveromyces marxianus1 6.70 0 100%

Seed sequence

2549 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

1MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES
61TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP
121VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP
181TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE
241AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC
301KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS PAKSTLVESR
361CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV
421LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA
481TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL
541KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT
601QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL
661VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS
721MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI
781LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA
841LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK
901VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR
961DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV
1021SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR
1081VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD
1141RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV
1201RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV ETGPMKKLHV
1261STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA
1321AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI
1381VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF
1441GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK
1501WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA
1561QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW
1621ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD
1681PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK
1741QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA
1801VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE SEAESTENSP
1861TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN
1921EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS
1981KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG
2041ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA
2101WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL
2161QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL
2221SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL
2281MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH
2341PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC
2401HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG
2461VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD
2521VPTQVELLIK QATSHENLCQ CYIGWCPFW

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 Structural basis for a phosphoinositide-driven mTORC2-AKT positive feedback loop Biorxiv doi:10.64898/2026.01.08.698367
2026 Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2. Science doi:10.1126/science.adv7111
2026 Structural basis of Wnt signalosome extracellular complex assembly. Cell doi:10.1016/j.cell.2026.05.006
2026 Structural basis for TORC2 activation. Mol.Cell doi:10.1016/j.molcel.2026.03.022
2025 Conformation-specific synthetic intrabodies modulate mTOR signaling with subcellular spatial resolution. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2424679122
2025 Mining the CRBN target space redefines rules for molecular glue-induced neosubstrate recognition. Science doi:10.1126/science.adt6736
2025 Structural basis for mTORC1 activation on the lysosomal membrane. Nature doi:10.1038/s41586-025-09545-3
2025 Asymmetric activation of dimeric ATM/Tel1 kinase. Cell Discov doi:10.1038/s41421-025-00786-0
2025 Structural Basis for the Recruitment and Selective Phosphorylation of Akt by mTORC2 Science doi:10.1126/science.adv711
2024 Structural insights into rapamycin-induced oligomerization of a FRB-FKBP fusion protein. Febs Lett. doi:10.1002/1873-3468.14986
2024 mTORC1 phosphorylates and stabilizes LST2 to negatively regulate EGFR. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2405959121
2023 Co-crystal structure of FKBP12, compound 7 and the FRB fragment of mTOR Chemrxiv doi:10.26434/chemrxiv-2023-4vb0m
2023 Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers. Cell Res. doi:10.1038/s41422-023-00830-2
2023 Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of mTORC1, for the Treatment of mTORC1-Activated Tumors. J.Med.Chem. doi:10.1021/acs.jmedchem.2c01658
2023 Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex. Nature doi:10.1038/s41586-022-05652-7
2023 EGOC inhibits TOROID polymerization by structurally activating TORC1. Nat.Struct.Mol.Biol. doi:10.1038/s41594-022-00912-6
2022 Interactions between mTORC2 core subunits Rictor and mSin1 dictate selective and context-dependent phosphorylation of substrate kinases SGK1 and Akt. J.Biol.Chem. doi:10.1016/j.jbc.2022.102288
2022 Structures of Mec1/ATR kinase endogenously stimulated by different genotoxins. Cell Discov doi:10.1038/s41421-022-00461-8
2021 Regulation of human mTOR complexes by DEPTOR. Elife doi:10.7554/eLife.70871
2021 Mechanism of auto-inhibition and activation of Mec1 ATR checkpoint kinase. Nat.Struct.Mol.Biol. doi:10.1038/s41594-020-00522-0
2021 Structures of human mGlu2 and mGlu7 homo- and heterodimers. Nature doi:10.1038/s41586-021-03641-w
2021 Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace. Elife doi:10.7554/eLife.68799
2020 Rational design and implementation of a chemically inducible heterotrimerization system. Nat.Methods doi:10.1038/s41592-020-0913-x
2020 The 3.2- angstrom resolution structure of human mTORC2. Sci Adv doi:10.1126/sciadv.abc1251
2019 Architecture of human Rag GTPase heterodimers and their complex with mTORC1. Science doi:10.1126/science.aax3939
2018 Cryo-EM structure of human mTOR complex 2. Cell Res. doi:10.1038/s41422-018-0029-3
2017 Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature doi:10.1038/nature25023
2017 3.9 angstrom structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP. Science doi:10.1126/science.aan8414
2017 Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2. Nat Commun doi:10.1038/s41467-017-01862-0
2016 Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25 and FRB in Live Cells Acs Cent.Sci. doi:10.1021/acscentsci.6b00137
2016 4.4 angstrom Resolution Cryo-EM structure of human mTOR Complex 1 Protein Cell doi:10.1007/s13238-016-0346-6
2016 Architecture of Human Mtor Complex 1 Science doi:10.1126/SCIENCE.AAA3870
2016 Tor Forms a Dimer Through an N-Terminal Helical Solenoid with a Complex Topology Nat.Commun. doi:10.1038/NCOMMS11016
2016 Structure of the human dimeric ATM kinase. Cell Cycle doi:10.1080/15384101.2016.1158362
2013 Large FK506-Binding Proteins Shape the Pharmacology of Rapamycin. Mol.Cell.Biol. doi:10.1128/MCB.00678-12
2013 mTOR kinase structure, mechanism and regulation. Nature doi:10.1038/nature12122
2012 Convenient method for resolving degeneracies due to symmetry of the magnetic susceptibility tensor and its application to pseudo contact shift-based protein-protein complex structure determination. J.Biomol.Nmr doi:10.1007/s10858-012-9623-8
2010 Structural Basis for the Association of the Redox-sensitive Target of Rapamycin FATC Domain with Membrane-mimetic Micelles. J.Biol.Chem. doi:10.1074/jbc.M109.058404
2008 Structural characterization of the interaction of mTOR with phosphatidic acid and a novel class of inhibitor: compelling evidence for a central role of the FRB domain in small molecule-mediated regulation of mTOR. Oncogene doi:10.1038/sj.onc.1210693
2006 The FRB Domain of mTOR: NMR Solution Structure and Inhibitor Design. Biochemistry doi:10.1021/bi060976+