Homo sapiens · seed P01308 · 110 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P01308 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 1.10.100.10 SCOP 8033230 SCOP 8038024 SCOP 8038097 SCOP 8072339 RCSB 8PI4 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.
8PI4, 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.
152 distinct constructs across 508 entries. 890 polymer entities differ from the UniProt canonical sequence in some way, 0 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 |
|---|---|---|---|---|
| 318 | 21 | 0.92 | 3W7Y | residues 90-110 |
| 154 | 30 | 0.92 | 3W7Y | residues 25-54 |
| 76 | 30 | 1.16 | 4IHN | residues 25-54; T54A |
| 35 | 29 | 1.20 | 4AJX | residues 25-53 |
| 34 | 21 | 1.16 | 4IHN | residues 85-105 |
| 20 | 70 | 1.60 | 1WQJ | residues 49-118 |
| 14 | 110 | 1.36 | 6TC2 | matches the canonical sequence |
| 12 | 21 | 1.40 | 9M4X | residues 90-110; N110G |
| 12 | 30 | 1.60 | 4IUZ | residues 25-54; H34D, P52K, K53P |
| 8 | 30 | 1.50 | 1ZEH | residues 25-54; P52D |
| 8 | 67 | 2.20 | 3KR3 | residues 25-91 |
| 7 | 195 | 3.24 | 8X06 | matches the canonical sequence |
| 6 | 26 | 1.88 | 8ONR | residues 25-50; Y50P |
| 6 | 30 | 1.17 | 5USP | residues 25-54 |
| 6 | 30 | 1.35 | 5UDP | residues 25-54; P52K, K53P |
| 5 | 30 | 1.70 | 3ZI3 | residues 25-54; F48H |
| 5 | 74 | 3.10 | 6PXW | residues 25-110; 1 internal deletion |
| 5 | 180 | 3.38 | 8YSZ | matches the canonical sequence |
| 4 | 22 | 2.00 | 2QIU | residues 89-110 |
| 4 | 25 | 3.60 | 7YQ3 | residues 27-51 |
| 4 | 30 | 1.40 | 4CY7 | residues 25-54; G32A |
| 4 | 30 | 2.30 | 5EMS | residues 25-54; K53L |
| 4 | 32 | 1.95 | 8WU0 | residues 25-56; R55K |
| 3 | 20 | 2.60 | 2WBY | residues 90-109 |
| 3 | 21 | 1.40 | 2BN3 | residues 85-105; A92T |
Showing the 25 most-used of 152.
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 | 193 | 38.0% |
| dodecameric | 12 | 131 | 25.8% |
| tetrameric | 4 | 63 | 12.4% |
| hexameric | 6 | 48 | 9.4% |
| monomeric | 1 | 28 | 5.5% |
| trimeric | 3 | 18 | 3.5% |
| octameric | 8 | 12 | 2.4% |
| pentameric | 5 | 8 | 1.6% |
308 entries have the depositor's assembly corroborated by PISA, 183 carry the depositor's word alone and 17 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 68 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1APH, 1B17, 1B18, 1B19, 1B2A, 1B2B, 1B2C, 1B2D, 1B2E, 1B2F, 1BEN, 1BPH, 1CPH, 1DEI, 1DPH, 1FU2, 1FUB, 1IZA, 1IZB, 1JCA.
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 |
|---|---|---|---|
| Insulin-like | CATH 1.10.100.10 | 27–93 | 26 |
| Insulin-like | SCOP2B 8033230 | 29–90 | 12 |
| Insulin-like | SCOP2B 8038024 | 90–110 | 333 |
| Insulin-like | SCOP2B 8038097 | 90–110 | 78 |
| Insulin-like | SCOP2B 8072339 | 90–110 | 72 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| ZN | ion | Zinc Ion | 171 | 0.92 |
| CL | ion | Chloride Ion | 126 | 1.20 |
| IPH | ligand | Phenol | 56 | 1.28 |
| SO4 | ion | Sulfate Ion | 34 | 1.30 |
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 26 | 2.30 |
| NA | ion | Sodium Ion | 25 | 1.08 |
| CRS | ligand | M-Cresol | 20 | 1.50 |
| GOL | cryoprotectant | Glycerol | 15 | 1.20 |
| RCO | ligand | Resorcinol | 12 | 1.20 |
| MYR | lipid/detergent | Myristic Acid | 9 | 1.40 |
| SCN | ion | Thiocyanate Ion | 7 | 1.30 |
| ACT | cryoprotectant | Acetate Ion | 7 | 0.95 |
| CU | ion | Copper (Ii) Ion | 7 | 1.12 |
| PO4 | ion | Phosphate Ion | 5 | 1.36 |
| DCE | ligand | 1,2-Dichloroethane | 4 | 1.90 |
| ACN | cryoprotectant | Acetone | 4 | 1.20 |
| C15 | ligand | N-Dodecyl-N,n-Dimethyl-3-Ammonio-1-Propanesulfonate | 4 | 2.00 |
| URE | ligand | Urea | 4 | 1.36 |
| NI | ion | Nickel (Ii) Ion | 4 | 1.35 |
| CO | ion | Cobalt (Ii) Ion | 3 | 1.20 |
Parsed from the free text 275 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 305
entries that recorded anything at all.
Median pH 7.0
(range 2.0 to 10.5).
502 entries carry a wwPDB validation report: 167 clean, 174 worth a check and 161 with something to explain. Median clashscore 8.78, median RSRZ outliers 3.97%, median R-free minus R-work 0.042. 453 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 394 | 0.92 | 206 | 100% |
| Sus scrofa | 42 | 1.20 | 13 | 78% |
| Bos taurus | 39 | 1.16 | 10 | 100% |
| Unknown | 27 | 1.00 | 22 | 46% |
| synthetic construct | 4 | 2.86 | 2 | 48% |
| Ovis aries | 3 | 4.30 | 2 | 26% |
| Mandarin fish ranavirus | 1 | 3.05 | 1 | 76% |
| Lymphocystis disease virus 1 | 1 | 4.60 | 0 | 74% |
| Balaenoptera physalus | 1 | 0 | 19% |
110 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 | Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity Elife doi:10.7554/elife.105761.3 |
| 2026 | An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling. Sci Adv doi:10.1126/sciadv.aeb7558 |
| 2026 | Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2. Nat Commun doi:10.1038/s41467-026-73851-1 |
| 2026 | Damping amyloid-associated conformational fluctuations in a protein by an engineered diselenide bridge. Protein Sci. doi:10.1002/pro.70697 |
| 2025 | Spitrobot-2 advances time-resolved cryo-trapping crystallography to under 25 ms. Commun Chem doi:10.1038/s42004-025-01784-9 |
| 2025 | Exploring humidity effects on polycrystalline human insulin-ligand complexes: preliminary crystallographic insights. J.Appl.Crystallogr. doi:10.1107/S1600576725007484 |
| 2025 | Triple Calcium Binding Stoichiometry in the Monoclinic Crystal Form of Protracted Insulin Small Struct doi:10.1002/sstr.202500398 |
| 2025 | IgE clonality and aggregation of insulin affect IgE-mediated activation of sensitized basophils. J Allergy Clin Immunol Glob doi:10.1016/j.jacig.2025.100502 |
| 2025 | Temperature induces a shift from insulin dihexamer to hexamer in collective dynamics. Protein Sci. doi:10.1002/pro.70245 |
| 2025 | X-ray crystallographic and hydrogen deuterium exchange studies confirm alternate kinetic models for homolog insulin monomers. Plos One doi:10.1371/journal.pone.0319282 |
| 2025 | Tuning insulin receptor signaling using de novo-designed agonists. Mol.Cell doi:10.1016/j.molcel.2025.09.020 |
| 2024 | Molecular engineering of insulin for recombinant expression in yeast. Trends Biotechnol doi:10.1016/j.tibtech.2023.09.012 |
| 2024 | Enhanced disulphide bond stability contributes to the once-weekly profile of insulin icodec. Nat Commun doi:10.1038/s41467-024-50477-9 |
| 2024 | A viral insulin-like peptide inhibits IGF-1 receptor phosphorylation and regulates IGF1R gene expression. Mol Metab doi:10.1016/j.molmet.2023.101863 |
| 2024 | Activation of the insulin receptor by insulin-like growth factor 2. Nat Commun doi:10.1038/s41467-024-46990-6 |
| 2024 | Atomic resolution structure of full-length human insulin fibrils. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2401458121 |
| 2023 | Comparative Study of High-Resolution LysB29(N epsilon-myristoyl) des(B30) Insulin Structures Display Novel Dynamic Causal Interrelations in Monomeric-Dimeric Motions Crystals doi:10.3390/cryst13040648 |
| 2023 | The T 2 structure of polycrystalline cubic human insulin. Acta Crystallogr D Struct Biol doi:10.1107/S2059798323001328 |
| 2023 | Structural basis of insulin fibrillation. Sci Adv doi:10.1126/sciadv.adi1057 |
| 2022 | ID23-2: an automated and high-performance microfocus beamline for macromolecular crystallography at the ESRF. J.Synchrotron Radiat. doi:10.1107/S1600577522000984 |
| 2022 | Serial macromolecular crystallography at ALBA Synchrotron Light Source. J.Synchrotron Radiat. doi:10.1107/S1600577522002508 |
| 2022 | Single-chain insulin analogs threaded by the insulin receptor alpha CT domain. Biophys.J. doi:10.1016/j.bpj.2022.09.038 |
| 2022 | Activation of the human insulin receptor by non-insulin-related peptides Nat Commun doi:10.1038/s41467-022-33315-8 |
| 2022 | Synergistic activation of the insulin receptor via two distinct sites. Nat.Struct.Mol.Biol. doi:10.1038/s41594-022-00750-6 |
| 2022 | Symmetric and asymmetric receptor conformation continuum induced by a new insulin. Nat.Chem.Biol. doi:10.1038/s41589-022-00981-0 |
| 2022 | Structural basis for assembly and disassembly of the IGF/IGFBP/ALS ternary complex Nat Commun doi:10.1038/s41467-022-32214-2 |
| 2022 | Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures. Nat Commun doi:10.1038/s41467-022-34292-8 |
| 2022 | How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor. Structure doi:10.1016/j.str.2022.05.007 |
| 2022 | Molecular basis for the role of disulfide-linked alpha CTs in the activation of insulin-like growth factor 1 receptor and insulin receptor. Elife doi:10.7554/eLife.81286 |
| 2022 | Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists. Nat Commun doi:10.1038/s41467-022-28561-9 |
| 2022 | Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist. Nat Commun doi:10.1038/s41467-022-34391-6 |
| 2022 | Structural Investigations of Full-Length Insulin Receptor Dynamics and Signalling. J.Mol.Biol. doi:10.1016/j.jmb.2022.167458 |
| 2021 | Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques. Sci Rep doi:10.1038/s41598-021-81251-2 |
| 2021 | Cell free protein synthesis versus yeast expression - A comparison using insulin as a model protein. Protein Expr.Purif. doi:10.1016/j.pep.2021.105910 |
| 2021 | Versatile microporous polymer-based supports for serial macromolecular crystallography. Acta Crystallogr D Struct Biol doi:10.1107/S2059798321007324 |
| 2021 | Insulin binding to the analytical antibody sandwich pair OXI-005 and HUI-018: Epitope mapping and binding properties. Protein Sci. doi:10.1002/pro.4009 |
| 2021 | Statistically correcting dynamical electron scattering improves the refinement of protein nanocrystals, including charge refinement of coordinated metals. Acta Crystallogr D Struct Biol doi:10.1107/S2059798320014540 |
| 2021 | Prion-derived tetrapeptide stabilizes thermolabile insulin via conformational trapping. Iscience doi:10.1016/j.isci.2021.102573 |
| 2020 | Insulin polymorphism induced by two polyphenols: new crystal forms and advances in macromolecular powder diffraction. Acta Crystallogr D Struct Biol doi:10.1107/S205979832001195X |
| 2020 | A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nat.Struct.Mol.Biol. doi:10.1038/s41594-020-0430-8 |