Homo sapiens · seed P42345 · 2549 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P42345 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 1.20.120.150 SCOP 8036936 SCOP 8083832 RCSB 9DL0 PDBe
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.
Every figure here is counted over the whole family rather than quoted from one entry.
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.
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.
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.
| Entities | Length | Best (Å) | Best entry | What 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.
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".
| Oligomeric state | Chains | Entries | Share |
|---|---|---|---|
| dimeric | 2 | 32 | 31.4% |
| octameric | 8 | 15 | 14.7% |
| tetrameric | 4 | 15 | 14.7% |
| trimeric | 3 | 11 | 10.8% |
| monomeric | 1 | 10 | 9.8% |
| dodecameric | 12 | 4 | 3.9% |
| decameric | 10 | 4 | 3.9% |
| pentameric | 5 | 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.
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.
| Domain | Source | Span (seed) | Chains |
|---|---|---|---|
| FKBP12-rapamycin binding domain | CATH 1.20.120.150 | 2020–2113 | 14 |
| FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP) | SCOP2B 8036936 | 2020–2112 | 60 |
| Frizzled domain-like | SCOP2B 8083832 | 2028–2145 | 2 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| IHP | ligand | Inositol Hexakisphosphate | 24 | 2.60 |
| ZN | ion | Zinc Ion | 17 | 2.20 |
| MG | ion | Magnesium Ion | 13 | 3.10 |
| RAP | ligand | Rapamycin Immunosuppressant Drug | 12 | 1.45 |
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 12 | 2.80 |
| ANP | cofactor | Phosphoaminophosphonic Acid-Adenylate Ester | 8 | 3.10 |
| GTP | cofactor | Guanosine-5'-Triphosphate | 6 | 3.20 |
| Z99 | ligand | 2-[(1s,2s)-2-Carboxycyclopropyl]-3-(9h-Xanthen-9-Yl)-D-Alanine | 6 | 2.80 |
| GDP | cofactor | Guanosine-5'-Diphosphate | 5 | 3.20 |
| ACE | ligand | Acetyl Group | 5 | 3.00 |
| ADP | cofactor | Adenosine-5'-Diphosphate | 4 | 2.60 |
| ATP | cofactor | Adenosine-5'-Triphosphate | 4 | 2.60 |
| CLR | lipid/detergent | Cholesterol | 4 | 2.90 |
| GLU | ligand | Glutamic Acid | 4 | 2.80 |
| AGS | cofactor | Phosphothiophosphoric Acid-Adenylate Ester | 3 | 3.00 |
| GSP | cofactor | 5'-Guanosine-Diphosphate-Monothiophosphate | 3 | 3.16 |
| RAD | ligand | C49-Methyl Rapamycin | 2 | 2.20 |
| ARD | ligand | C15-(R)-Methylthienyl Rapamycin | 2 | 1.85 |
| MGF | ligand | Trifluoromagnesate | 2 | 3.50 |
| SO4 | ion | Sulfate Ion | 2 | 1.80 |
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).
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.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 87 | 1.45 | 67 | 100% |
| Saccharomyces cerevisiae | 7 | 2.93 | 3 | 99% |
| Saccharomyces cerevisiae S288C | 5 | 3.80 | 1 | 99% |
| Schizosaccharomyces pombe 972h- | 1 | 3.63 | 1 | 16% |
| Schizosaccharomyces pombe | 1 | 4.32 | 0 | 16% |
| Kluyveromyces marxianus | 1 | 6.70 | 0 | 100% |
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
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.
One record per paper, not per entry.
| Year | Citation |
|---|---|
| 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+ |