Homo sapiens · seed P22303 · 614 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P22303 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 3.40.50.1820 SCOP 8042208 SCOP 8032481 SCOP 8086463 SCOP 8032473 SCOP 8033793 SCOP 8032490 SCOP 8042176 SCOP 8032600 SCOP 8071846 RCSB 6O5V 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.
6O5V, 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 562 entries. 529 polymer entities differ from the UniProt canonical sequence in some way, 28 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 |
|---|---|---|---|---|
| 61 | 529 | 1.85 | 6ZWI | residues 29-557; N45Q, N483Q, N509Q +1 more |
| 53 | 537 | 1.80 | 1EA5 | residues 22-558 |
| 37 | 542 | 2.00 | 4M0E | residues 33-574 |
| 37 | 543 | 2.05 | 2HA2 | residues 32-574 |
| 31 | 548 | 2.10 | 4B82 | residues 32-581; 1 internal deletion; D575A, E581P |
| 30 | 543 | 2.05 | 1W6R | residues 22-564 |
| 20 | 550 | 2.15 | 6O5V | residues 29-578; V29G, G30P, A31L |
| 13 | 570 | 1.95 | 4FNG | M364L, I419F, A472T +3 more |
| 12 | 532 | 1.85 | 7B38 | residues 25-556 |
| 11 | 577 | 1.53 | 5CH5 | His6; D83A, M364L, I419F +4 more |
| 8 | 532 | 1.86 | 5A7F | residues 21-553; 1 internal deletion |
| 8 | 534 | 2.10 | 5EI5 | residues 23-556 |
| 8 | 543 | 2.60 | 2XUI | residues 32-574; Y368A |
| 7 | 586 | 1.75 | 7AIS | matches the canonical sequence |
| 6 | 529 | 2.10 | 2WIJ | residues 29-557; N45Q, N483Q, N509Q |
| 6 | 565 | 1.79 | 6G1U | residues 22-586 |
| 5 | 527 | 2.10 | 2XQF | residues 31-557; N45Q, N483Q, N509Q +1 more |
| 5 | 547 | 1.75 | 6H1A | His8; residues 17-553; V17L, A18Y, S19F +4 more |
| 5 | 549 | 2.18 | 1LPM | matches the canonical sequence |
| 5 | 557 | 1.90 | 6QAA | residues 1-557; H2D, N45Q, N483Q +2 more |
| 5 | 870 | 3.22 | 8G7Z | 3C/PreScission site; 1 internal deletion; 17-residue insertion after 12; M1G, W2A, L3P +5 more |
| 4 | 529 | 2.10 | 2XMB | residues 29-557; N45Q, G145H, N483Q +2 more |
| 4 | 529 | 2.60 | 6F7Q | residues 29-557 |
| 4 | 540 | 1.79 | 9D1K | matches the canonical sequence |
| 4 | 540 | 2.45 | 7E3H | residues 35-574 |
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 | 317 | 56.4% |
| monomeric | 1 | 186 | 33.1% |
| tetrameric | 4 | 18 | 3.2% |
| octameric | 8 | 18 | 3.2% |
| trimeric | 3 | 14 | 2.5% |
| hexameric | 6 | 5 | 0.9% |
| pentameric | 5 | 4 | 0.7% |
332 entries have the depositor's assembly corroborated by PISA, 202 carry the depositor's word alone and 28 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 23 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1F8U, 1KU6, 1LPN, 1LPP, 1P0I, 1P0P, 1U4N, 1XLU, 1XLV, 1XLW, 2H7C, 3DJY, 3DKK, 3K9B, 3O9M, 3RAR, 3VKF, 4AQD, 4BDT, 4FNG.
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 |
|---|---|---|---|
| Alpha/Beta hydrolase fold, catalytic domain | CATH 3.40.50.1820 | 38–572 | 450 |
| alpha/beta-Hydrolases | SCOP2B 8042208 | 32–573 | 96 |
| alpha/beta-Hydrolases | SCOP2B 8032481 | 36–573 | 75 |
| alpha/beta-Hydrolases | SCOP2B 8086463 | 36–572 | 5 |
| alpha/beta-Hydrolases | SCOP2B 8032473 | 38–569 | 123 |
| alpha/beta-Hydrolases | SCOP2B 8033793 | 38–563 | 109 |
| alpha/beta-Hydrolases | SCOP2B 8032490 | 56–587 | 6 |
| alpha/beta-Hydrolases | SCOP2B 8042176 | 59–590 | 20 |
| alpha/beta-Hydrolases | SCOP2B 8032600 | 77–610 | 7 |
| alpha/beta-Hydrolases | SCOP2B 8071846 | 109–614 | 6 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 369 | 1.48 |
| SO4 | ion | Sulfate Ion | 146 | 1.50 |
| CL | ion | Chloride Ion | 129 | 1.75 |
| GOL | cryoprotectant | Glycerol | 105 | 1.30 |
| EDO | cryoprotectant | 1,2-Ethanediol | 58 | 1.10 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 55 | 1.10 |
| P6G | cryoprotectant | Hexaethylene Glycol | 53 | 1.79 |
| MES | buffer | 2-(N-Morpholino)-Ethanesulfonic Acid | 51 | 1.86 |
| NA | ion | Sodium Ion | 33 | 1.89 |
| SIA | cofactor | N-Acetyl-Alpha-Neuraminic Acid | 29 | 2.00 |
| PGE | cryoprotectant | Triethylene Glycol | 29 | 1.79 |
| PG4 | cryoprotectant | Tetraethylene Glycol | 24 | 1.79 |
| CA | ion | Calcium Ion | 23 | 2.00 |
| NO3 | ion | Nitrate Ion | 21 | 2.00 |
| ACT | cryoprotectant | Acetate Ion | 19 | 1.10 |
| HI6 | ligand | 4-(Aminocarbonyl)-1-[({2-[(E)-(Hydroxyimino)methyl]pyridinium-1- | 17 | 2.15 |
| PG0 | ligand | 2-(2-Methoxyethoxy)ethanol | 17 | 2.10 |
| DPF | ligand | Diethyl Hydrogen Phosphate | 16 | 1.53 |
| UNX | ion | Unknown Atom Or Ion | 14 | 2.10 |
| VX | ligand | O-Ethylmethylphosphonic Acid Ester Group | 14 | 2.10 |
Parsed from the free text 504 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 530
entries that recorded anything at all.
Median pH 6.5
(range 4.2 to 9.0).
562 entries carry a wwPDB validation report: 343 clean, 122 worth a check and 97 with something to explain. Median clashscore 6.44, median RSRZ outliers 1.69%, median R-free minus R-work 0.039. 538 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 228 | 1.48 | 211 | 100% |
| Tetronarce californica | 124 | 1.75 | 109 | 99% |
| Mus musculus | 109 | 2.00 | 104 | 95% |
| Lucilia cuprina | 38 | 1.10 | 23 | 82% |
| Anopheles gambiae | 7 | 1.79 | 5 | 89% |
| Diutina rugosa | 9 | 1.97 | 8 | 64% |
| Thermobifida fusca | 4 | 1.39 | 3 | 82% |
| Bos taurus | 4 | 1.60 | 3 | 88% |
| Rattus norvegicus | 4 | 1.80 | 3 | 88% |
| Alicyclobacillus acidocaldarius | 4 | 2.00 | 2 | 16% |
| Drosophila melanogaster | 4 | 2.15 | 3 | 88% |
| Bacillus subtilis | 3 | 1.50 | 0 | 82% |
614 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 and evolutionary constraints of organophosphate resistance in dipteran carboxylesterases. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2517957123 |
| 2026 | Potent and selective indole-based inhibitors targeting disease-transmitting mosquitoes. Rsc Med Chem doi:10.1039/d5md00797f |
| 2026 | Leveraging multitargeting BChE-MAO B inhibitors against microglia-related neuroinflammation: in vitro biological evaluation, structure-activity relationships, drug-like properties, and X-ray crystal complexes. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2026.118961 |
| 2026 | Design, synthesis and evaluation of an uncharged broad spectrum quinoline-oxime hybrid for the reactivation of nerve agent-inhibited human acetylcholinesterase. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2026.119023 |
| 2026 | Integrative structural and kinetic analysis of the molecular basis for reduced carbamate inhibition in atypical butyrylcholinesterase. Chem.Biol.Interact. doi:10.1016/j.cbi.2026.112134 |
| 2026 | An improved nerve agent bioscavenger based on the fast self-reactivation mechanism of porcine butyrylcholinesterase. Protein Sci. doi:10.1002/pro.70467 |
| 2026 | Dual Inhibitors J.Med.Chem. doi:10.1021/acs.jmedchem.6c01461 |
| 2026 | Structure-Guided Design and Synthesis of Selective Butyrylcholinesterase Inhibitors J.Mol.Struct. doi:10.1016/j.molstruc.2026.145611 |
| 2026 | Structures of distinct human acetylcholinesterase tetramer forms in complex with synaptic anchoring proteins Structure doi:10.1016/j.str.2026.08.016 |
| 2026 | Weaker neuroligin 2-neurexin beta 1 interaction tethers membranes and recruits gephyrin at membrane junctions through clustering. Sci Adv doi:10.1126/sciadv.ads9732 |
| 2025 | Heat-sterilizable antibody mimics designed on the cold shock protein scaffold from hyperthermophile Thermotoga maritima. Protein Sci. doi:10.1002/pro.70018 |
| 2025 | Chiral switch of a butyrylcholinesterase inhibitor for the treatment of Alzheimer's disease. Chem.Biol.Interact. doi:10.1016/j.cbi.2025.111670 |
| 2025 | N-Propargylpyrrolidine-based butyrylcholinesterase and monoamine oxidase inhibitors. Chem.Biol.Interact. doi:10.1016/j.cbi.2025.111681 |
| 2025 | Understanding the molecular mechanism of fumonisin esterases by kinetic and structural studies. Food Chem doi:10.1016/j.foodchem.2025.143110 |
| 2025 | Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38 alpha Mitogen-Activated Protein Kinase Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00933 |
| 2025 | Kinetic and structural evidence for specific DMSO interference with reversible binding of uncharged bis-oximes to hAChE and their reactivation kinetics of OP-hAChE. Chem.Biol.Interact. doi:10.1016/j.cbi.2025.111649 |
| 2025 | Multifunctional, Fluorene-Based Modulator of Cholinergic and GABAergic Neurotransmission as a Novel Drug Candidate for Palliative Treatment of Alzheimer's Disease. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202420510 |
| 2025 | The product of Ellman's reaction inhibits cholinesterases. Protein Sci. doi:10.1002/pro.70371 |
| 2025 | Dual cholinergic modulation in dementia: Quinuclidine carbamates targeting butyrylcholinesterase and alpha 7 nicotinic receptor. Chem.Biol.Interact. doi:10.1016/j.cbi.2025.111830 |
| 2025 | Lead Optimization of a Butyrylcholinesterase Inhibitor for the Treatment of Alzheimer's Disease. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00577 |
| 2024 | The study of halogen effect on the reactivity of the serine-targeting covalent warheads. Front Chem doi:10.3389/fchem.2024.1504453 |
| 2024 | Disentangling the formation, mechanism, and evolvement of the covalent methanesulfonyl fluoride acetylcholinesterase adduct: Insights into an aged-like inactive complex susceptible to reactivation by a combination of nucleophiles. Protein Sci. doi:10.1002/pro.4977 |
| 2024 | Enzyme Dynamics Determine the Potency and Selectivity of Inhibitors Targeting Disease-Transmitting Mosquitoes. Acs Infect Dis. doi:10.1021/acsinfecdis.4c00531 |
| 2023 | Rapid discovery and crystallography study of highly potent and selective butylcholinesterase inhibitors based on oxime-containing libraries and conformational restriction strategies. Bioorg.Chem. doi:10.1016/j.bioorg.2023.106465 |
| 2023 | 8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases. Acta Pharm Sin B doi:10.1016/j.apsb.2023.01.013 |
| 2023 | Pseudo-irreversible butyrylcholinesterase inhibitors: Structure-activity relationships, computational and crystallographic study of the N-dialkyl O-arylcarbamate warhead. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2022.115048 |
| 2023 | Discovery of new, highly potent and selective inhibitors of BuChE - design, synthesis, in vitro and in vivo evaluation and crystallography studies. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2023.115135 |
| 2023 | Structure of an antennally-expressed carboxylesterase suggests lepidopteran odorant degrading enzymes are broadly tuned Curr Res Insect Sci doi:10.1016/j.cris.2023.100062 |
| 2023 | Highly selective butyrylcholinesterase inhibitors related to Amaryllidaceae alkaloids - Design, synthesis, and biological evaluation. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2023.115301 |
| 2023 | High-resolution structural-omics of human liver enzymes. Cell Rep doi:10.1016/j.celrep.2023.112609 |
| 2022 | Structural Insights into (Tere)phthalate-Ester Hydrolysis by a Carboxylesterase and Its Role in Promoting PET Depolymerization Acs Catalysis doi:10.1021/acscatal.2c03772 |
| 2022 | The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1. Int J Mol Sci doi:10.3390/ijms232113101 |
| 2022 | From tryptophan-based amides to tertiary amines: Optimization of a butyrylcholinesterase inhibitor series. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2022.114248 |
| 2022 | Structural and dynamic effects of paraoxon binding to human acetylcholinesterase by X-ray crystallography and inelastic neutron scattering. Structure doi:10.1016/j.str.2022.09.006 |
| 2022 | Broad-Spectrum Antidote Discovery by Untangling the Reactivation Mechanism of Nerve-Agent-Inhibited Acetylcholinesterase. Chemistry doi:10.1002/chem.202200678 |
| 2022 | Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2022.05.009 |
| 2022 | Grid-Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions. Chembiochem doi:10.1002/cbic.202200456 |
| 2022 | Dual Reversible Coumarin Inhibitors Mutually Bound to Monoamine Oxidase B and Acetylcholinesterase Crystal Structures. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.2c00001 |
| 2022 | A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning. J.Med.Chem. doi:10.1021/acs.jmedchem.1c01748 |
| 2022 | Cryo-EM structure of native human thyroglobulin. Nat Commun doi:10.1038/s41467-021-27693-8 |