CODSWALLOP

Insulin

Homo sapiens · seed P01308 · 110 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.

508Entries 923Entities 152Constructs 8Organisms 256Ligand-bound
0.92 ÅBest res.
1.95 ÅMedian res.

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

The reference structure

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.

Rendered structure of 8PI4
8PI4 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.

155110506 constructs

Constructs, most-used first

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.

EntitiesLengthBest (Å)Best entryWhat 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.

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".

T54A 24% K53P 21% P52K 20% T97F 20% H34E 18% I99S 18% Y50F 14% N110A 14% T51N 12% F49Y 11% Y40Q 11% Y103R 11% S33A 10% E37D 10% L41F 10% S98R 10% Q94E 10% S101D 10% Q104R 10% N107M 10% E45D 10% E93D 7% H29T 7% N27S 6% Q28E 6% V26P 5% F25R 4% F48H 3% A38T 3% V92L 2%

What it assembles into

Oligomeric stateChainsEntriesShare
dimeric2 193 38.0%
dodecameric12 131 25.8%
tetrameric4 63 12.4%
hexameric6 48 9.4%
monomeric1 28 5.5%
trimeric3 18 3.5%
octameric8 12 2.4%
pentameric5 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.

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.

CATHInsulin-likeSCOP2BInsulin-likeInsulin-likeInsulin-likeInsulin-like155110
DomainSourceSpan (seed)Chains
Insulin-likeCATH 1.10.100.10 27–93 26
Insulin-likeSCOP2B 8033230 29–90 12
Insulin-likeSCOP2B 8038024 90–110 333
Insulin-likeSCOP2B 8038097 90–110 78
Insulin-likeSCOP2B 8072339 90–110 72

What binds it

IPH IPH56 entries NAG NAG26 entries CRS CRS20 entries RCO RCO12 entries DCE DCE4 entries C15 C154 entries URE URE4 entries SRO SRO3 entries TYL TYL2 entries MPB MPB2 entries 16E 16E2 entries ARG ARG2 entries
ComponentClassNameEntriesBest (Å)
ZNion Zinc Ion 171 0.92
CLion Chloride Ion 126 1.20
IPHligand Phenol 56 1.28
SO4ion Sulfate Ion 34 1.30
NAGcofactor 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose 26 2.30
NAion Sodium Ion 25 1.08
CRSligand M-Cresol 20 1.50
GOLcryoprotectant Glycerol 15 1.20
RCOligand Resorcinol 12 1.20
MYRlipid/detergent Myristic Acid 9 1.40
SCNion Thiocyanate Ion 7 1.30
ACTcryoprotectant Acetate Ion 7 0.95
CUion Copper (Ii) Ion 7 1.12
PO4ion Phosphate Ion 5 1.36
DCEligand 1,2-Dichloroethane 4 1.90
ACNcryoprotectant Acetone 4 1.20
C15ligand N-Dodecyl-N,n-Dimethyl-3-Ammonio-1-Propanesulfonate 4 2.00
UREligand Urea 4 1.36
NIion Nickel (Ii) Ion 4 1.35
COion Cobalt (Ii) Ion 3 1.20

How it crystallises

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).

Precipitants

Sodium citrate × PEG × Sodium chloride × Ammonium sulfate × Ethanol × MPD × Dioxane × Magnesium chloride × Lithium sulfate × Isopropanol × Calcium chloride × Tacsimate × Sodium formate × PEG (unspecified) ×

Buffers

Citrate × Tris × Phosphate × HEPES × Sodium acetate × Imidazole × MES × Sodium cacodylate × CAPS × Bis-Tris × Bis-Tris propane ×

Which entries to trust

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.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens394 0.92 206 100%
Sus scrofa42 1.20 13 78%
Bos taurus39 1.16 10 100%
Unknown27 1.00 22 46%
synthetic construct4 2.86 2 48%
Ovis aries3 4.30 2 26%
Mandarin fish ranavirus1 3.05 1 76%
Lymphocystis disease virus 11 4.60 0 74%
Balaenoptera physalus1 0 19%

Seed sequence

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

1MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED
61LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC SLYQLENYCN

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 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