CODSWALLOP

Prothrombin

Homo sapiens · seed P00734 · 622 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.

1,402Entries 1,988Entities 397Constructs 14Organisms 1,588Ligand-bound
0.85 ÅBest res.
2.00 ÅMedian res.

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

The reference structure

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.

Rendered structure of 1DOJ
1DOJ 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.

13116221327 constructs

Constructs, most-used first

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.

EntitiesLengthBest (Å)Best entryWhat 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.

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".

M374E 64% A473T 64% I372A 64% Y497T 62% S368Q 62% D597K 62% Q619S 62% D595A 62% H605K 61% L609Y 61% E366G 61% S375W 61% R456S 61% P534S 61% R461N 61% D538S 61% M585T 61% E565Q 61% K610V 61% R436G 61% F607S 61% D618K 61% M380S 61% N420S 61% V535S 60% V616T 60% R399Q 60% M466L 60% L528V 60% E371K 60%

What it assembles into

Oligomeric stateChainsEntriesShare
trimeric3 458 32.7%
dimeric2 438 31.2%
monomeric1 362 25.8%
tetrameric4 101 7.2%
pentameric5 16 1.1%
hexameric6 13 0.9%
octameric8 6 0.4%
dodecameric12 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.

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.

CATHLamininHepatocyte Growth FactorPlasminogen Kringle 4Thrombin light chain domaiTrypsin-like serine proteaSCOP2BHairpin loop containing doEGF/Laminin-likeKringle-likeTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine protea1311622
DomainSourceSpan (seed)Chains
LamininCATH 2.10.25.10 49–182 47
Hepatocyte Growth FactorCATH 3.50.4.10 117–206 40
Plasminogen Kringle 4CATH 2.40.20.10 121–208 82
Thrombin light chain domainCATH 4.10.140.10 320–363 20
Trypsin-like serine proteasesCATH 2.40.10.10 466–573 2,508
Hairpin loop containing domain-likeSCOP2B 8036022 117–205 19
EGF/Laminin-likeSCOP2B 8035338 130–180 43
Kringle-likeSCOP2B 8036023 206–288 22
Trypsin-like serine proteasesSCOP2B 8042154 364–621 160
Trypsin-like serine proteasesSCOP2B 8035341 364–596 131
Trypsin-like serine proteasesSCOP2B 8037496 364–586 115
Trypsin-like serine proteasesSCOP2B 8044201 364–600 105

What binds it

NAG NAG292 entries 0G6 0G662 entries BEN BEN58 entries FUC FUC35 entries BGC BGC23 entries 0GJ 0GJ12 entries ANH ANH10 entries GSH GSH10 entries GBS GBS8 entries 0Z6 0Z67 entries 6PL 6PL7 entries ACA ACA5 entries
ComponentClassNameEntriesBest (Å)
CAion Calcium Ion 481 0.85
NAion Sodium Ion 325 1.05
NAGcofactor 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose 292 0.92
SO4ion Sulfate Ion 281 0.85
GOLcryoprotectant Glycerol 230 0.85
CLion Chloride Ion 94 1.18
EDOcryoprotectant 1,2-Ethanediol 80 1.00
PO4ion Phosphate Ion 80 1.12
DMScryoprotectant Dimethyl Sulfoxide 73 1.00
0G6ligand D-Phenylalanyl-N-[(2s,3s)-6-{[Amino(Iminio)methyl]amino}-1-Chlor 62 1.30
BENligand Benzamidine 58 0.85
MGion Magnesium Ion 47 1.19
FUCcofactor Alpha-L-Fucopyranose 35 1.25
ZNion Zinc Ion 27 1.30
CITbuffer Citric Acid 26 1.25
BGCligand Beta-D-Glucopyranose 23 1.72
ACTcryoprotectant Acetate Ion 23 1.08
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 20 0.97
Kion Potassium Ion 20 1.58
PEGcryoprotectant Di(Hydroxyethyl)ether 17 1.18

How it crystallises

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).

Precipitants

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

Buffers

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

Which entries to trust

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.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens1,148 0.92 1401 100%
Bos taurus172 0.85 143 92%
Sus scrofa49 1.18 20 65%
Mus musculus13 1.94 13 78%
Streptomyces griseus7 1.05 3 39%
Daboia siamensis4 1.80 4 41%
Pseudonaja textilis2 2.71 2 42%
Gloydius halys1 1.75 0 41%
Drosophila melanogaster1 1.75 1 13%
Holotrichia diomphalia1 2.00 0 41%
Eisenia fetida1 2.06 0 41%
Ovis aries1 2.10 1 41%

Seed sequence

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

1MAHVRGLQLP GCLALAALCS LVHSQHVFLA PQQARSLLQR VRRANTFLEE VRKGNLEREC
61VEETCSYEEA FEALESSTAT DVFWAKYTAC ETARTPRDKL AACLEGNCAE GLGTNYRGHV
121NITRSGIECQ LWRSRYPHKP EINSTTHPGA DLQENFCRNP DSSTTGPWCY TTDPTVRRQE
181CSIPVCGQDQ VTVAMTPRSE GSSVNLSPPL EQCVPDRGQQ YQGRLAVTTH GLPCLAWASA
241QAKALSKHQD FNSAVQLVEN FCRNPDGDEE GVWCYVAGKP GDFGYCDLNY CEEAVEEETG
301DGLDEDSDRA IEGRTATSEY QTFFNPRTFG SGEADCGLRP LFEKKSLEDK TERELLESYI
361DGRIVEGSDA EIGMSPWQVM LFRKSPQELL CGASLISDRW VLTAAHCLLY PPWDKNFTEN
421DLLVRIGKHS RTRYERNIEK ISMLEKIYIH PRYNWRENLD RDIALMKLKK PVAFSDYIHP
481VCLPDRETAA SLLQAGYKGR VTGWGNLKET WTANVGKGQP SVLQVVNLPI VERPVCKDST
541RIRITDNMFC AGYKPDEGKR GDACEGDSGG PFVMKSPFNN RWYQMGIVSW GEGCDRDGKY
601GFYTHVFRLK KWIQKVIDQF GE

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 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