Homo sapiens · seed P08684 · 503 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P08684 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 1.10.630.10 SCOP 8103386 SCOP 8040388 SCOP 8068663 SCOP 8039120 SCOP 8084082 SCOP 8064340 SCOP 8032216 RCSB 1TQN 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.
1TQN, 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.
62 distinct constructs across 197 entries. 184 polymer entities differ from the UniProt canonical sequence in some way, 14 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 |
|---|---|---|---|---|
| 95 | 487 | 1.70 | 5VCC | residues 21-503; L21M, L22A |
| 11 | 486 | 2.05 | 1TQN | residues 22-503; L22M, Y23A |
| 6 | 485 | 2.00 | 3NXU | residues 23-503; Y23M, L24A |
| 5 | 480 | 2.20 | 6MJM | residues 22-501; L22M, Y23A, T498H +3 more |
| 4 | 487 | 2.40 | 7UFE | residues 21-503; L21M, L22A, K421A +1 more |
| 3 | 416 | 1.54 | 3P3O | matches the canonical sequence |
| 3 | 417 | 2.10 | 1IZO | matches the canonical sequence |
| 3 | 487 | 1.95 | 5VCD | residues 21-503; L21M, L22A, C58A +5 more |
| 3 | 487 | 2.10 | 3N9Y | His6; residues 41-521 |
| 3 | 489 | 2.77 | 6XZ9 | His6; residues 24-503; L24M, G25A, R27K |
| 2 | 444 | 2.10 | 2VE3 | matches the canonical sequence |
| 2 | 466 | 1.75 | 7YD9 | residues 1-466; 1 internal deletion; F88G, A185V, T269V +9 more |
| 2 | 468 | 2.77 | 4ZF8 | residues 1-468; R48L, F82I, F88V +9 more |
| 2 | 483 | 2.49 | 4DVQ | His6; residues 27-503; R27M, A29K, R30K +3 more |
| 2 | 484 | 2.40 | 9NJW | no UniProt reference for this entity, so it cannot be diffed against a canonical sequence |
| 2 | 484 | 2.95 | 4NY4 | residues 24-503; L24A |
| 2 | 487 | 1.93 | 4D6Z | residues 21-503; L21M, L22A, K282A +1 more |
| 2 | 492 | 1.68 | 7WZM | His6+T7 |
| 2 | 503 | matches the canonical sequence | ||
| 1 | 390 | 2.30 | 9KPU | residues 8-397; A10T, A11P, D22A +83 more |
| 1 | 393 | 1.85 | 9KPP | residues 5-397; E6S, G7A, A10T +85 more |
| 1 | 406 | 2.10 | 3P3L | P144A |
| 1 | 407 | 1.94 | 3VM4 | residues 9-415 |
| 1 | 407 | 2.17 | 3VNO | residues 9-415; R241E |
| 1 | 407 | 2.34 | 3VOO | residues 9-415; A245E |
Showing the 25 most-used of 62.
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 |
|---|---|---|---|
| monomeric | 1 | 95 | 48.2% |
| dimeric | 2 | 81 | 41.1% |
| tetrameric | 4 | 9 | 4.6% |
| trimeric | 3 | 8 | 4.1% |
| hexameric | 6 | 4 | 2.0% |
74 entries have the depositor's assembly corroborated by PISA, 113 carry the depositor's word alone and 8 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 22 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1TQN, 4I3Q, 4I4G, 4I4H, 4NY4, 5VC0, 5VCC, 5VCD, 5VCE, 5VCG, 6MA6, 6MA7, 6UNE, 6UNG, 6UNH, 6UNI, 6UNJ, 6UNK, 6UNL, 6UNM.
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 |
|---|---|---|---|
| Cytochrome P450 | CATH 1.10.630.10 | 31–499 | 113 |
| Cytochrome P450 | SCOP2B 8103386 | 27–499 | 2 |
| Cytochrome P450 | SCOP2B 8040388 | 30–498 | 121 |
| Cytochrome P450 | SCOP2B 8068663 | 31–497 | 6 |
| Cytochrome P450 | SCOP2B 8039120 | 284–503 | 17 |
| Cytochrome P450 | SCOP2B 8084082 | 305–503 | 4 |
| Cytochrome P450 | SCOP2B 8064340 | 358–503 | 6 |
| Cytochrome P450 | SCOP2B 8032216 | 362–503 | 5 |
HEM194 entries
RIT5 entries
FES5 entries
MYT4 entries
PAM3 entries
STR3 entries
MWY3 entries
IC63 entries
HOA3 entries
HL03 entries
KLN2 entries
HC92 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| HEM | cofactor | Protoporphyrin Ix Containing Fe | 194 | 1.32 |
| GOL | cryoprotectant | Glycerol | 35 | 1.32 |
| SO4 | ion | Sulfate Ion | 13 | 1.54 |
| EDO | cryoprotectant | 1,2-Ethanediol | 13 | 1.70 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 7 | 1.32 |
| RIT | ligand | Ritonavir | 5 | 2.00 |
| PLM | lipid/detergent | Palmitic Acid | 5 | 1.65 |
| FES | ligand | Fe2/s2 (Inorganic) Cluster | 5 | 2.10 |
| CL | ion | Chloride Ion | 5 | 1.54 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 5 | 2.00 |
| MYT | ligand | Metyrapone | 4 | 1.40 |
| PAM | ligand | Palmitoleic Acid | 3 | 2.00 |
| STR | ligand | Progesterone | 3 | 2.45 |
| MWY | ligand | (3as,4r,5s,6r,8r,9r,9ar,10r)-6-Ethyl-5-Hydroxy-4,6,9,10-Tetramet | 3 | 2.46 |
| MRD | cryoprotectant | (4r)-2-Methylpentane-2,4-Diol | 3 | 1.65 |
| IMD | buffer | Imidazole | 3 | 1.78 |
| NI | ion | Nickel (Ii) Ion | 3 | 2.77 |
| IC6 | ligand | (2s)-2-(6-Imidazol-1-Ylhexanoylamino)-3-Phenyl-Propanoic Acid | 3 | 1.75 |
| HOA | ligand | Hydroxyamine | 3 | 1.56 |
| HL0 | ligand | N-[(3s)-2-Oxotetrahydrofuran-3-Yl]decanamide | 3 | 1.32 |
Parsed from the free text 189 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 190
entries that recorded anything at all.
Median pH 7.0
(range 5.0 to 9.0).
194 entries carry a wwPDB validation report: 82 clean, 65 worth a check and 47 with something to explain. Median clashscore 8.4, median RSRZ outliers 2.41%, median R-free minus R-work 0.044. 194 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 150 | 1.40 | 150 | 100% |
| Priestia megaterium | 12 | 1.32 | 12 | 44% |
| Sphingomonas paucimobilis | 7 | 1.65 | 7 | 21% |
| Priestia megaterium NBRC 15308 = ATCC 14581 | 5 | 1.52 | 5 | 43% |
| Bacillus subtilis | 5 | 2.00 | 5 | 20% |
| Streptomyces thioluteus | 4 | 1.54 | 4 | 33% |
| Streptomyces avermitilis | 2 | 1.68 | 2 | 41% |
| Actinomadura sp. | 2 | 1.85 | 2 | 34% |
| Synechocystis sp. PCC 6803 | 2 | 2.10 | 2 | 36% |
| Taxus cuspidata | 2 | 2.10 | 2 | 42% |
| Bacillus subtilis subsp. subtilis str. 168 | 2 | 2.29 | 2 | 20% |
| synthetic construct | 2 | 2.40 | 2 | 40% |
503 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 | The role of CYP3A-CYP2E1 interactions in activation of CYP3A enzymes by chronic alcohol exposure Biochem.J. doi:10.1042/bcj20260456 |
| 2025 | Rationally designing P450BM3-H to excavate a novel channel for product exit and enhance overall performance. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2025.142162 |
| 2025 | Interaction of cytochrome P450 3A4 with the hydrophilic ligand tetraethylene glycol. Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2025.153040 |
| 2025 | Cytochrome P450 Mediated Cyclohexane Ring Formation in Forazoline Biosynthesis. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202504925 |
| 2025 | Decoding the selective chemical modulation of CYP3A4. Nat Commun doi:10.1038/s41467-025-58749-8 |
| 2025 | Interaction of cytochrome P450 3A4 with cannabinoids and the drug darifenacin. J.Biol.Chem. doi:10.1016/j.jbc.2025.110709 |
| 2025 | Unexpected Activities of CYP152 Peroxygenases Toward Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202506614 |
| 2025 | Evaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4. Chem.Biol.Drug Des. doi:10.1111/cbdd.70043 |
| 2025 | How evolution shaped the structure of steroidogenic cytochrome P450 11A. J.Inorg.Biochem. doi:10.1016/j.jinorgbio.2025.113105 |
| 2025 | Unique structural features define the decarboxylation activity of a CYP152 fatty acid decarboxylase from Lacicoccus alkaliphilus. J.Biol.Chem. doi:10.1016/j.jbc.2025.110397 |
| 2025 | Microcrystallization and room-temperature serial crystallography structure of human cytochrome P450 3A4. Arch.Biochem.Biophys. doi:10.1016/j.abb.2025.110419 |
| 2024 | Bacterial Acyl Homoserine Lactones Triggered Non-Native Substrate Hydroxylation Catalyzed by Directed-Evolution-Derived Cytochrome P450BM3 Mutants Chemcatchem doi:10.1002/cctc.202401641 |
| 2024 | Revisiting strategies and their combinatorial effect for introducing peroxygenase activity in CYP102A1 (P450BM3) Mol Catal doi:10.1016/j.mcat.2024.113953 |
| 2024 | Unraveling the Catalytic Mechanism of Taxadiene-5alpha-hydroxylase from Crystallography and Computational Analyses. Acs Catalysis doi:10.1021/acscatal.3c05807 |
| 2024 | Interaction of CYP3A4 with the inhibitor cobicistat: Structural and mechanistic insights and comparison with ritonavir. Arch.Biochem.Biophys. doi:10.1016/j.abb.2024.110071 |
| 2024 | Directed Evolution Enables Dynamic Control of Transient Intermediates for Anti-Markovnikov Wacker-Tsuji-Type Oxidation of Unactivated Alkenes Chemrxiv doi:10.26434/chemrxiv-2024-j0229-v2 |
| 2023 | Regiodivergent and Enantioselective Hydroxylation of C-H bonds by Synergistic Use of Protein Engineering and Exogenous Dual-Functional Small Molecules. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202215088 |
| 2023 | Dynamic Ir(III) Photosensors for the Major Human Drug-Metabolizing Enzyme Cytochrome P450 3A4. Inorg.Chem. doi:10.1021/acs.inorgchem.3c00059 |
| 2023 | Interaction of CYP3A4 with caffeine: First insights into multiple substrate binding. J.Biol.Chem. doi:10.1016/j.jbc.2023.105117 |
| 2023 | Biocatalytic enantioselective gamma-C-H lactonization of aliphatic carboxylic acids Nat Synth doi:10.1038/s44160-023-00427-y |
| 2023 | Human cytochrome P450 3A7 binding four copies of its native substrate dehydroepiandrosterone 3-sulfate. J.Biol.Chem. doi:10.1016/j.jbc.2023.104993 |
| 2023 | Differential Effects of Clotrimazole on X-Ray Crystal Structures of Human Cytochromes P450 3A5 and 3A4. Drug Metab.Dispos. doi:10.1124/dmd.123.001464 |
| 2022 | Biocatalytic Enantioselective beta-Hydroxylation of Unactivated C-H Bonds in Aliphatic Carboxylic Acids. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202204290 |
| 2022 | Interaction of CYP3A4 with Rationally Designed Ritonavir Analogues: Impact of Steric Constraints Imposed on the Heme-Ligating Group and the End-Pyridine Attachment. Int J Mol Sci doi:10.3390/ijms23137291 |
| 2022 | Crystal Structure of CYP3A4 Complexed with Fluorol Identifies the Substrate Access Channel as a High-Affinity Ligand Binding Site. Int J Mol Sci doi:10.3390/ijms232012591 |
| 2022 | Structural characterization of the homotropic cooperative binding of azamulin to human cytochrome P450 3A5. J.Biol.Chem. doi:10.1016/j.jbc.2022.101909 |
| 2022 | Ir(III)-Based Agents for Monitoring the Cytochrome P450 3A4 Active Site Occupancy. Inorg.Chem. doi:10.1021/acs.inorgchem.2c02587 |
| 2021 | Spatially restricted substrate-binding site of cortisol-synthesizing CYP11B1 limits multiple hydroxylations and hinders aldosterone synthesis. Curr Res Struct Biol doi:10.1016/j.crstbi.2021.08.001 |
| 2021 | Structural Basis for the Diminished Ligand Binding and Catalytic Ability of Human Fetal-Specific CYP3A7. Int J Mol Sci doi:10.3390/ijms22115831 |
| 2021 | Photosensitive Ru(II) Complexes as Inhibitors of the Major Human Drug Metabolizing Enzyme CYP3A4. J.Am.Chem.Soc. doi:10.1021/jacs.1c04155 |
| 2021 | Rational Design of CYP3A4 Inhibitors: A One-Atom Linker Elongation in Ritonavir-Like Compounds Leads to a Marked Improvement in the Binding Strength. Int J Mol Sci doi:10.3390/ijms22020852 |
| 2021 | Unraveling the Structural Basis of Selective Inhibition of Human Cytochrome P450 3A5. J.Am.Chem.Soc. doi:10.1021/jacs.1c07066 |
| 2021 | Innovative C 2 -symmetric testosterone and androstenedione dimers: Design, synthesis, biological evaluation on prostate cancer cell lines and binding study to recombinant CYP3A4. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2021.113496 |
| 2021 | Structural and functional insights into aldosterone synthase interaction with its redox partner protein adrenodoxin. J.Biol.Chem. doi:10.1016/j.jbc.2021.100794 |
| 2021 | Aldosterone Synthase Structure With Cushing Disease Drug LCI699 Highlights Avenues for Selective CYP11B Drug Design. Hypertension doi:10.1161/HYPERTENSIONAHA.121.17615 |
| 2020 | An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4. Bioorg.Med.Chem. doi:10.1016/j.bmc.2020.115349 |
| 2020 | Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.0c00233 |
| 2019 | Interaction of Human Drug-Metabolizing CYP3A4 with Small Inhibitory Molecules. Biochemistry doi:10.1021/acs.biochem.8b01221 |
| 2019 | Structure of human cortisol-producing cytochrome P450 11B1 bound to the breast cancer drug fadrozole provides insights for drug design. J. Biol. Chem. doi:10.1074/jbc.RA118.006214 |
| 2019 | Structure-Activity Relationships of Rationally Designed Ritonavir Analogues: Impact of Side-Group Stereochemistry, Headgroup Spacing, and Backbone Composition on the Interaction with CYP3A4. Biochemistry doi:10.1021/acs.biochem.9b00156 |