Homo sapiens · seed Q9Y5Y9 · 1956 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt Q9Y5Y9 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 2.60.40.10 CATH 1.20.120.350 CATH 1.10.287.70 CATH 1.10.238.10 CATH 1.20.5.1190 RCSB 7WE4 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.
7WE4, 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.
47 distinct constructs across 101 entries. 81 polymer entities differ from the UniProt canonical sequence in some way, 55 carry a recognised expression tag and 10 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 |
|---|---|---|---|---|
| 8 | 1988 | 2.70 | 21TQ | matches the canonical sequence |
| 8 | 2031 | 2.90 | 7W9P | FLAG+Strep-II; E406K |
| 7 | 1596 | 2.60 | 6A95 | FLAG+Strep-II |
| 7 | 1980 | 2.50 | 25II | matches the canonical sequence |
| 4 | 1608 | 2.20 | 8F0P | FLAG+Strep-II; F270S, V274L, L275I +78 more |
| 4 | 1838 | 3.24 | 6UZ0 | fused to GFP (internal); residues 1-1906; 2 internal deletions; 13-residue insertion after 1899; R1899E, R1900Y, H1902D +4 more |
| 4 | 1956 | 2.70 | 7WE4 | S894F |
| 4 | 2001 | 2.76 | 9DBN | FLAG+Strep-II; TEV site; M1713V |
| 4 | 2028 | 2.60 | 8I5Y | FLAG+Strep-II |
| 3 | 288 | 3.54 | 6N4I | FLAG; Thrombin site; 1 internal deletion; 4-residue insertion after 89; G26T, I27L, T28F +39 more |
| 3 | 296 | 2.60 | 8VGL | FLAG; Thrombin site; 2 internal deletions; 14-residue insertion after 89; G26M, I27V, G30M +29 more |
| 3 | 2016 | 3.48 | 9P24 | matches the canonical sequence |
| 3 | 2250 | 3.07 | 7XMF | Strep-II; fused to GFP; 3C/PreScission site; 1 internal deletion; W1161R |
| 2 | 277 | 3.20 | 6W6O | residues 722-1010; 2 internal deletions; 1-residue insertion after 767; L722M, I723K, W724M +186 more |
| 2 | 1559 | 3.40 | 6NT3 | FLAG+Strep-II; residues 1-1505; F270S, V274L, L275I +78 more |
| 2 | 1737 | 2.90 | 7TJ9 | FLAG+Strep-II |
| 2 | 2022 | 2.70 | 7XVE | FLAG+Strep-II; E156K, G779R, L866F +8 more |
| 2 | 2059 | 3.30 | 6LQA | FLAG+Strep-II |
| 1 | 35 | 1.35 | 4DJC | residues 1488-1522; T1488S, E1489N, E1490A |
| 1 | 51 | 2.25 | 5DBR | residues 1479-1529; K1479G, L1480P, G1482S |
| 1 | 53 | residues 1474-1526 | ||
| 1 | 97 | residues 1769-1865; A1769G, I1770P, I1771G +1 more | ||
| 1 | 129 | residues 1751-1882; 2 internal deletions; V1751M, I1753S, F1754S +15 more | ||
| 1 | 140 | 2.69 | 6MUD | residues 1783-1922; T1783S, E1784N, P1785A |
| 1 | 157 | 2.80 | 4OVN | residues 1773-1929 |
Showing the 25 most-used of 47.
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 |
|---|---|---|---|
| trimeric | 3 | 39 | 38.6% |
| monomeric | 1 | 28 | 27.7% |
| dimeric | 2 | 24 | 23.8% |
| octameric | 8 | 5 | 5.0% |
| tetrameric | 4 | 2 | 2.0% |
| dodecameric | 12 | 2 | 2.0% |
| pentameric | 5 | 1 | 1.0% |
18 entries have the depositor's assembly corroborated by PISA, 83 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: 4DCK.
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 |
|---|---|---|---|
| Immunoglobulins | CATH 2.60.40.10 | 40–159 | 5 |
| Voltage-gated potassium channels. Chain C | CATH 1.20.120.350 | 883–1022 | 9 |
| 1.10.287.70 | CATH | 1293–1382 | 5 |
| EF-hand | CATH 1.10.238.10 | 1727–1844 | 8 |
| iswi atpase | CATH 1.20.5.1190 | 1846–1878 | 3 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 75 | 2.20 |
| LPE | ligand | 1-O-Octadecyl-Sn-Glycero-3-Phosphocholine | 36 | 2.20 |
| Y01 | lipid/detergent | Cholesterol Hemisuccinate | 35 | 2.20 |
| PCW | lipid/detergent | 1,2-Dioleoyl-Sn-Glycero-3-Phosphocholine | 35 | 2.20 |
| P5S | ligand | O-[(R)-{[(2r)-2,3-Bis(Octadecanoyloxy)propyl]oxy}(Hydroxy)phosph | 29 | 2.20 |
| 9Z9 | ligand | (3beta,14beta,17beta,25r)-3-[4-Methoxy-3-(Methoxymethyl)butoxy]s | 26 | 2.20 |
| CLR | lipid/detergent | Cholesterol | 17 | 2.50 |
| 6OU | ligand | [(2~{R})-1-[2-Azanylethoxy(Oxidanyl)phosphoryl]oxy-3-Hexadecanoy | 13 | 3.20 |
| NA | ion | Sodium Ion | 11 | 2.20 |
| 1PW | ligand | (2s,3r,4e)-2-(Acetylamino)-3-Hydroxyoctadec-4-En-1-Yl Dihydrogen | 7 | 2.20 |
| CA | ion | Calcium Ion | 6 | 1.35 |
| P3X | ligand | (5e,17r,20s)-23-Amino-20-Hydroxy-14,20-Dioxo-15,19,21-Trioxa-20l | 5 | 2.50 |
| 9SL | ligand | [(3as,4r,10as)-2,6-Diamino-10,10-Dihydroxy-3a,4,9,10-Tetrahydro- | 5 | 2.90 |
| 9SR | ligand | (1r,5r,6r,7r,9s,11s,12s,13s,14s)-3-Amino-14-(Hydroxymethyl)-8,10 | 5 | 2.60 |
| POV | ligand | (2s)-3-(Hexadecanoyloxy)-2-[(9z)-Octadec-9-Enoyloxy]propyl 2-(Tr | 4 | 2.90 |
| PEE | lipid/detergent | 1,2-Dioleoyl-Sn-Glycero-3-Phosphoethanolamine | 4 | 2.20 |
| 95T | ligand | 5-(4-Chlorophenyl)-~{N}-(3,5-Dimethoxyphenyl)furan-2-Carboxamide | 3 | 2.70 |
| BMA | cofactor | Beta-D-Mannopyranose | 3 | 2.50 |
| A1E26 | ligand | Veratridine | 2 | 2.70 |
| MG | ion | Magnesium Ion | 2 | 2.20 |
Parsed from the free text 11 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 11
entries that recorded anything at all.
Median pH 6.5
(range 4.0 to 9.5).
101 entries carry a wwPDB validation report: 65 clean, 20 worth a check and 16 with something to explain. Median clashscore 10.6, median RSRZ outliers 1.89%, median R-free minus R-work 0.034. 100 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 75 | 1.35 | 64 | 100% |
| Periplaneta americana | 9 | 2.60 | 9 | 93% |
| Rattus norvegicus | 8 | 3.20 | 7 | 95% |
| Aliarcobacter butzleri RM4018 | 5 | 2.60 | 1 | 22% |
| Halalkalibacterium halodurans C-125 | 2 | 3.20 | 2 | 14% |
| Escherichia coli K-12 | 1 | 3.60 | 0 | 8% |
| Electrophorus electricus | 1 | 4.00 | 0 | 95% |
1956 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 | Diverse binding poses of agonistic neurotoxins on human Na v 1.6. Nature doi:10.1038/s41586-026-10661-x |
| 2026 | Optical control of the cardiac rhythm with photoswitchable Na V 1.5 channel blockers. Nat Commun doi:10.1038/s41467-026-70305-6 |
| 2026 | Structural and functional mechanisms underlying activation gate dynamics and IFM motif accessibility in human Na v 1.5. Nat Commun doi:10.1038/s41467-026-69672-x |
| 2025 | Structural basis of inhibition of human Na V 1.8 by the tarantula venom peptide Protoxin-I. Nat Commun doi:10.1038/s41467-024-55764-z |
| 2025 | Critical role of extracellular loops in differential modulations of TTX-sensitive and TTX-resistant Na v channels. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2510355122 |
| 2025 | Structural basis of human Na v 1.5 gating mechanisms. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2416181122 |
| 2024 | Disulfi de constrained Fabs overcome target size limitation for high-resolution single-particle cryo-EM. Biorxiv doi:10.1101/2024.05.10.593593 |
| 2024 | Dissection of the structure-function relationship of Na v channels. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2322899121 |
| 2024 | Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin. Nat Commun doi:10.1038/s41467-024-45958-w |
| 2024 | Scorpion alpha-toxin Lqh alpha IT specifically interacts with a glycan at the pore domain of voltage-gated sodium channels. Structure doi:10.1016/j.str.2024.07.021 |
| 2023 | Cryo-EM reveals an unprecedented binding site for Na V 1.7 inhibitors enabling rational design of potent hybrid inhibitors. Elife doi:10.7554/eLife.84151 |
| 2023 | Structural mapping of Na v 1.7 antagonists. Nat Commun doi:10.1038/s41467-023-38942-3 |
| 2023 | Dual-pocket inhibition of Na v channels by the antiepileptic drug lamotrigine. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2309773120 |
| 2023 | Cannabidiol inhibits Na v channels through two distinct binding sites. Nat Commun doi:10.1038/s41467-023-39307-6 |
| 2023 | Cryo-EM structure of human voltage-gated sodium channel Na v 1.6. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2220578120 |
| 2023 | Structural basis for inhibition of the cardiac sodium channel by the atypical antiarrhythmic drug ranolazine. Nat Cardiovasc Res doi:10.1038/s44161-023-00271-5 |
| 2023 | Structure of human Na V 1.6 channel reveals Na + selectivity and pore blockade by 4,9-anhydro-tetrodotoxin. Nat Commun doi:10.1038/s41467-023-36766-9 |
| 2022 | High-resolution structures of human Na v 1.7 reveal gating modulation through alpha-pi helical transition of S6 IV. Cell Rep doi:10.1016/j.celrep.2022.110735 |
| 2022 | Structural basis for high-voltage activation and subtype-specific inhibition of human Na v 1.8. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2208211119 |
| 2022 | Unwinding and spiral sliding of S4 and domain rotation of VSD during the electromechanical coupling in Na v 1.7. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2209164119 |
| 2022 | Structure-guided unlocking of Na X reveals a non-selective tetrodotoxin-sensitive cation channel. Nat Commun doi:10.1038/s41467-022-28984-4 |
| 2022 | Structural basis for Na V 1.7 inhibition by pore blockers. Nat.Struct.Mol.Biol. doi:10.1038/s41594-022-00860-1 |
| 2022 | Structural basis for modulation of human Na V 1.3 by clinical drug and selective antagonist. Nat Commun doi:10.1038/s41467-022-28808-5 |
| 2021 | Structural Basis for Pore Blockade of the Human Cardiac Sodium Channel Na v 1.5 by the Antiarrhythmic Drug Quinidine*. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202102196 |
| 2021 | Structure of human Na v 1.5 reveals the fast inactivation-related segments as a mutational hotspot for the long QT syndrome. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2100069118 |
| 2021 | Comparative structural analysis of human Na v 1.1 and Na v 1.5 reveals mutational hotspots for sodium channelopathies. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2100066118 |
| 2021 | Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin. Nat Commun doi:10.1038/s41467-020-20078-3 |
| 2021 | Open-state structure and pore gating mechanism of the cardiac sodium channel. Cell doi:10.1016/j.cell.2021.08.021 |
| 2021 | Structural Basis for High-Affinity Trapping of the Na V 1.7 Channel in Its Resting State by Tarantula Toxin. Mol.Cell doi:10.1016/j.molcel.2020.10.039 |
| 2020 | Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na + channels in nanodisc. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.1922903117 |
| 2020 | Structure of the Cardiac Sodium Channel. Cell doi:10.1016/j.cell.2019.11.041 |
| 2019 | Ca2+-dependent regulation of sodium channels NaV1.4 and NaV1.5 is controlled by the post-IQ motif. Nat Commun doi:10.1038/s41467-019-09570-7 |
| 2019 | Crystal structures of Ca2+-calmodulin bound to NaVC-terminal regions suggest role for EF-hand domain in binding and inactivation. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.1818618116 |
| 2019 | Molecular basis for pore blockade of human Na+channel Nav1.2 by the mu-conotoxin KIIIA. Science doi:10.1126/science.aaw2999 |
| 2019 | Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science doi:10.1126/science.aaw2493 |
| 2019 | Cryo-EM structures of a human-cockroach hybrid Nav channel in the presence and absence of the alpha-scorpion toxin AaH2. Science |
| 2019 | Structural basis of alpha-scorpion toxin action on Na v channels. Science doi:10.1126/science.aav8573 |
| 2019 | Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin. Cell doi:10.1016/j.cell.2018.12.018 |
| 2018 | Structural basis for the modulation of voltage-gated sodium channels by animal toxins. Science doi:10.1126/science.aau2596 |
| 2018 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta 1. Science doi:10.1126/science.aau2486 |