Homo sapiens · seed P00734 · 622 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P00734 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 2.10.25.10 CATH 3.50.4.10 CATH 2.40.20.10 CATH 4.10.140.10 CATH 2.40.10.10 SCOP 8036022 SCOP 8035338 SCOP 8036023 SCOP 8042154 SCOP 8035341 SCOP 8037496 SCOP 8044201 SCOP 8036522 SCOP 8035635 SCOP 8032586 RCSB 1DOJ 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.
1DOJ, 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.
397 distinct constructs across 1,402 entries. 1,948 polymer entities differ from the UniProt canonical sequence in some way, 73 carry a recognised expression tag and 3 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 |
|---|---|---|---|---|
| 322 | 36 | 1.23 | 3RM2 | residues 328-363 |
| 308 | 259 | 1.12 | 4UD9 | residues 364-622 |
| 102 | 254 | 1.36 | 5PAG | residues 213-466 |
| 82 | 223 | 0.85 | 4I8K | residues 24-246 |
| 46 | 254 | 1.55 | 4Y6D | residues 235-488 |
| 39 | 134 | 1.55 | 4Y6D | residues 46-179 |
| 37 | 244 | 1.55 | 5TKS | His6; residues 388-625; N491G, T493G |
| 28 | 234 | 1.50 | 2PR3 | residues 235-468 |
| 28 | 238 | 0.92 | 7MBO | residues 388-625; C500S |
| 26 | 257 | 1.30 | 2CF8 | residues 364-620 |
| 24 | 259 | 1.60 | 7A0D | residues 367-625 |
| 23 | 238 | 1.25 | 4CRG | residues 388-625; S452A, K455A, T493A +1 more |
| 22 | 223 | 1.25 | 1S83 | residues 9-231 |
| 21 | 152 | 1.40 | 4YLQ | residues 61-212 |
| 20 | 49 | 1.60 | 7A0D | residues 318-366 |
| 19 | 258 | 1.12 | 5AFY | residues 364-621 |
| 17 | 27 | 1.54 | 1VZQ | residues 334-360 |
| 17 | 245 | 1.65 | 4MPU | residues 31-275; R51H, D52G, R53P +1 more |
| 16 | 29 | 1.12 | 5AFY | residues 333-361 |
| 16 | 235 | 1.90 | 1G2L | residues 235-469 |
| 15 | 233 | 1.62 | 2P3U | residues 235-467 |
| 13 | 142 | 1.72 | 2C4F | residues 61-202 |
| 12 | 259 | 1.60 | 3B9F | residues 364-622; S568A |
| 11 | 183 | 1.90 | 5CP9 | residues 28-210; A29V |
| 11 | 241 | 1.30 | 1EAX | residues 615-855 |
Showing the 25 most-used of 397.
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 | 458 | 32.7% |
| dimeric | 2 | 438 | 31.2% |
| monomeric | 1 | 362 | 25.8% |
| tetrameric | 4 | 101 | 7.2% |
| pentameric | 5 | 16 | 1.1% |
| hexameric | 6 | 13 | 0.9% |
| octameric | 8 | 6 | 0.4% |
| dodecameric | 12 | 5 | 0.4% |
921 entries have the depositor's assembly corroborated by PISA, 425 carry the depositor's word alone and 56 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 55 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1BBR, 1DM4, 1FIZ, 1GHY, 1IOD, 1KLI, 1MKW, 1MKX, 1NL0, 1O0D, 1RD3, 1SG8, 1TBR, 1THS, 1TQ0, 1UCY, 1VIT, 1X7A, 1XKB, 1XMN.
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 |
|---|---|---|---|
| Laminin | CATH 2.10.25.10 | 49–182 | 47 |
| Hepatocyte Growth Factor | CATH 3.50.4.10 | 117–206 | 40 |
| Plasminogen Kringle 4 | CATH 2.40.20.10 | 121–208 | 82 |
| Thrombin light chain domain | CATH 4.10.140.10 | 320–363 | 20 |
| Trypsin-like serine proteases | CATH 2.40.10.10 | 466–573 | 2,508 |
| Hairpin loop containing domain-like | SCOP2B 8036022 | 117–205 | 19 |
| EGF/Laminin-like | SCOP2B 8035338 | 130–180 | 43 |
| Kringle-like | SCOP2B 8036023 | 206–288 | 22 |
| Trypsin-like serine proteases | SCOP2B 8042154 | 364–621 | 160 |
| Trypsin-like serine proteases | SCOP2B 8035341 | 364–596 | 131 |
| Trypsin-like serine proteases | SCOP2B 8037496 | 364–586 | 115 |
| Trypsin-like serine proteases | SCOP2B 8044201 | 364–600 | 105 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| CA | ion | Calcium Ion | 481 | 0.85 |
| NA | ion | Sodium Ion | 325 | 1.05 |
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 292 | 0.92 |
| SO4 | ion | Sulfate Ion | 281 | 0.85 |
| GOL | cryoprotectant | Glycerol | 230 | 0.85 |
| CL | ion | Chloride Ion | 94 | 1.18 |
| EDO | cryoprotectant | 1,2-Ethanediol | 80 | 1.00 |
| PO4 | ion | Phosphate Ion | 80 | 1.12 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 73 | 1.00 |
| 0G6 | ligand | D-Phenylalanyl-N-[(2s,3s)-6-{[Amino(Iminio)methyl]amino}-1-Chlor | 62 | 1.30 |
| BEN | ligand | Benzamidine | 58 | 0.85 |
| MG | ion | Magnesium Ion | 47 | 1.19 |
| FUC | cofactor | Alpha-L-Fucopyranose | 35 | 1.25 |
| ZN | ion | Zinc Ion | 27 | 1.30 |
| CIT | buffer | Citric Acid | 26 | 1.25 |
| BGC | ligand | Beta-D-Glucopyranose | 23 | 1.72 |
| ACT | cryoprotectant | Acetate Ion | 23 | 1.08 |
| MES | buffer | 2-(N-Morpholino)-Ethanesulfonic Acid | 20 | 0.97 |
| K | ion | Potassium Ion | 20 | 1.58 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 17 | 1.18 |
Parsed from the free text 1,072 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 1,154
entries that recorded anything at all.
Median pH 7.3
(range 4.0 to 10.5).
1,402 entries carry a wwPDB validation report: 617 clean, 409 worth a check and 376 with something to explain. Median clashscore 6.45, median RSRZ outliers 3.14%, median R-free minus R-work 0.038. 1,171 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 1,148 | 0.92 | 1401 | 100% |
| Bos taurus | 172 | 0.85 | 143 | 92% |
| Sus scrofa | 49 | 1.18 | 20 | 65% |
| Mus musculus | 13 | 1.94 | 13 | 78% |
| Streptomyces griseus | 7 | 1.05 | 3 | 39% |
| Daboia siamensis | 4 | 1.80 | 4 | 41% |
| Pseudonaja textilis | 2 | 2.71 | 2 | 42% |
| Gloydius halys | 1 | 1.75 | 0 | 41% |
| Drosophila melanogaster | 1 | 1.75 | 1 | 13% |
| Holotrichia diomphalia | 1 | 2.00 | 0 | 41% |
| Eisenia fetida | 1 | 2.06 | 0 | 41% |
| Ovis aries | 1 | 2.10 | 1 | 41% |
622 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 | X-ray Diffraction Analyses of Trypsin Crystals Grown in the Presence of Additives Cryst.Growth Des. doi:10.1021/acs.cgd.5c01305 |
| 2026 | A 3.3- angstrom cryo-EM structure of an engineered high-affinity human prothrombinase complex. Blood doi:10.1182/blood.2025031527 |
| 2026 | N ‐Alkyl and N ‐Aryl Aminopyrazole Spirocarbamates: A Two-Pronged Lead Optimization Strategy to Identify Orally Bioavailable Plasma Kallikrein Inhibitors. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00066 |
| 2026 | Prothrombinase processivity is conferred by substrate allostery. Embo J. doi:10.1038/s44318-026-00782-4 |
| 2026 | TMPRSS2-mediated coronavirus spike activation and inhibition. Nat.Struct.Mol.Biol. doi:10.1038/s41594-026-01801-y |
| 2026 | Complete inhibition of beta-tryptase by tetramer dissociation and active site allostery due to a single antibody residue. Nat Commun doi:10.1038/s41467-026-70491-3 |
| 2026 | Anticoagulation with mechanistically distinct FXI/FXIa antibodies amrecibart (REGN9933A2) and cenvacibart (REGN7508Cat). Blood doi:10.1182/blood.2025032276 |
| 2026 | Structural insights into the exosite-mediated activation of factor IX by factor XIa using cryogenic electron microscopy. J.Thromb.Haemost. doi:10.1016/j.jtha.2026.08.015 |
| 2026 | Structural requirements of blood factors binding to soluble hexon trimers with implications for adenovirus cell targeting and immune evasion. Plos Pathog. doi:10.1371/journal.ppat.1014389 |
| 2026 | Molecular mechanism of cleavage at R271 during prothrombin activation revealed by cryo-EM. Blood doi:10.1182/blood.2025032364 |
| 2025 | Large Library Docking and Biophysical Analysis of Small-Molecule TMPRSS2 Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.4c03089 |
| 2025 | Small molecule inhibitors of mannan-binding lectin-associated serine Proteases-2 and-3. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.117238 |
| 2025 | Discovery of BAY 3389934 Hydrochloride: A Potent and Selective Small-Molecule Dual Factor IIa/Xa Inhibitor with Short Half-Life for the Acute Treatment of Sepsis-Induced Coagulopathy. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00538 |
| 2025 | The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies. Nat Commun doi:10.1038/s41467-025-62023-2 |
| 2025 | Integrating Surface Plasmon Resonance and Docking Analysis for Mechanistic Insights of Tryptase Inhibitors. Molecules doi:10.3390/molecules30061338 |
| 2025 | The in vitro and crystallographic studies reveal the inhibitory potential of vitamin B 6 analogues against a serine protease trypsin. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2025.142433 |
| 2025 | Structural determination of a new non-canonical inhibition complex between porcine trypsin and M271 a potato Kunitz-STI inhibitor. Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2025.151818 |
| 2025 | Replacement of a single residue changes the primary specificity of thrombin. J.Thromb.Haemost. doi:10.1016/j.jtha.2024.12.024 |
| 2025 | Engineering ultrapotent trivalent anticoagulants through hybridisation of salivary peptides from multiple haematophagous organisms. Chem Sci doi:10.1039/d5sc04734j |
| 2025 | Molecular basis of vitamin K-dependent protein gamma-glutamyl carboxylation. Cell Res. doi:10.1038/s41422-025-01185-6 |
| 2025 | Cryo-EM structure of coagulation factor Va bound to activated protein C. Blood doi:10.1182/blood.2025028476 |
| 2025 | Blocking activation of the C1r zymogen defines a novel mode of complement inhibition. J.Biol.Chem. doi:10.1016/j.jbc.2025.108301 |
| 2025 | Monoclonal antibodies against human TMPRSS2 prevent infection by any SARS-CoV-2 variant. Iscience doi:10.1016/j.isci.2025.113424 |
| 2025 | A TMPRSS6-inhibiting mAb improves disease in a beta-thalassemia mouse model and reduces iron in healthy humans. JCI Insight doi:10.1172/jci.insight.191813 |
| 2025 | Molecular basis of vitamin-K-driven gamma-carboxylation at the membrane interface. Nature doi:10.1038/s41586-025-08648-1 |
| 2025 | Cryo-EM structure of the tissue factor/factor VIIa complex with a factor X mimetic reveals a novel allosteric mechanism. Blood doi:10.1182/blood.2025029430 |
| 2024 | Discovery of potent small-molecule inhibitors of lipoprotein(a) formation. Nature doi:10.1038/s41586-024-07387-z |
| 2024 | Mechanism-Based Macrocyclic Inhibitors of Serine Proteases. J.Med.Chem. doi:10.1021/acs.jmedchem.3c02388 |
| 2024 | Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin. Protein Sci. doi:10.1002/pro.5110 |
| 2024 | Alternative Linkage Chemistries in the Chemoenzymatic Synthesis of Microviridin-Based Cyclic Peptides. Org.Lett. doi:10.1021/acs.orglett.3c04045 |
| 2024 | Water-medicated specifically targeting the S1 pockets among serine proteases using an arginine analogue. Bioorg.Chem. doi:10.1016/j.bioorg.2024.107734 |
| 2024 | Structural basis of TMPRSS2 zymogen activation and recognition by the HKU1 seasonal coronavirus. Cell doi:10.1016/j.cell.2024.06.007 |
| 2024 | An RNA aptamer exploits exosite-dependent allostery to achieve specific inhibition of coagulation factor IXa. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2401136121 |
| 2024 | Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors. Nat Commun doi:10.1038/s41467-024-48211-6 |
| 2024 | In vitro , in silico and crystallographic-based identification of serine protease inhibitors. Nat Prod Res doi:10.1080/14786419.2024.2425793 |
| 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 | High-resolution crystal structure of human coronavirus HKU1 receptor binding domain bound to TMPRSS2 receptor Hlife doi:10.1016/j.hlife.2024.09.005 |
| 2024 | Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling. Elife doi:10.7554/eLife.71980 |
| 2024 | Structural basis for the recognition of HCoV-HKU1 by human TMPRSS2. Cell Res. doi:10.1038/s41422-024-00958-9 |
| 2024 | Human coronavirus HKU1 recognition of the TMPRSS2 host receptor. Cell doi:10.1016/j.cell.2024.06.006 |