Homo sapiens · seed P09874 · 1014 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P09874 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 3.30.1740.10 CATH 1.10.20.130 CATH 2.20.25.630 CATH 3.40.50.10190 CATH 1.20.142.10 CATH 3.90.228.10 SCOP 8074102 SCOP 8039231 SCOP 8036812 SCOP 8037412 SCOP 8037018 SCOP 8036814 RCSB 7S6H 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.
7S6H, 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.
68 distinct constructs across 165 entries. 176 polymer entities differ from the UniProt canonical sequence in some way, 22 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 |
|---|---|---|---|---|
| 15 | 357 | 1.80 | 4GV2 | residues 176-532; V176S, T177M |
| 13 | 271 | 1.50 | 6NRH | residues 722-1012; 3 internal deletions; Q722M, D726H, S727H +29 more |
| 8 | 350 | 2.10 | 8HE7 | residues 662-1011; V762A |
| 8 | 352 | 1.59 | 9ETQ | residues 660-1011; T661S, V762A |
| 8 | 352 | 1.90 | 5WS1 | residues 660-1011; G660H, T661M, V762A |
| 7 | 353 | 2.10 | 8HKO | residues 229-581; K229G, T349S, L351R +2 more |
| 6 | 361 | 2.25 | 1A26 | residues 651-1011; K651A |
| 5 | 352 | 1.70 | 7KK2 | residues 660-1011; T661S |
| 5 | 355 | 1.82 | 9ETR | residues 658-1011; 1-residue insertion after 659; N658G, T661S, V762A |
| 4 | 116 | 2.40 | 3OD8 | His6; Thrombin site; residues 1-96 |
| 4 | 276 | 3.10 | 7S6H | His6; Thrombin site; residues 1-366; 1 internal deletion |
| 4 | 350 | 2.80 | 2RCW | residues 662-1011 |
| 4 | 358 | 2.20 | 4R6E | residues 661-1014; T661M, V762A, S1012A +2 more |
| 4 | 368 | 1.95 | 3KJD | residues 216-579; 4-residue insertion after 232; E216M, E217H, T218H +14 more |
| 3 | 160 | 1.70 | 2RIQ | residues 215-374; G215M, A367L, T368E +6 more |
| 3 | 267 | 3.31 | 4OPX | residues 1-374; 1 internal deletion; E205D, G206I, A367L +7 more |
| 3 | 354 | 2.49 | 9ILN | residues 658-1011; N658G, G660M, V762A |
| 3 | 372 | 2.10 | 6VKK | residues 643-1011; 3-residue insertion after 660; I643M, D644G, Y645S +14 more |
| 3 | 504 | 3.10 | 7S6H | His6; residues 517-1014; 1 internal deletion; N517M, V762A |
| 3 | 505 | 3.31 | 4OPX | His6; residues 518-1014 |
| 3 | 590 | 3.90 | 6X0L | His6; Thrombin site; 1 internal deletion |
| 2 | 111 | 2.80 | 3ODC | residues 104-214; S104M, K207L, R208E +6 more |
| 2 | 123 | 3.28 | 9ZQA | residues 90-212 |
| 2 | 131 | 2.80 | 6F5B | residues 88-218; L88S, K89M |
| 2 | 131 | 3.50 | 7SCZ | residues 362-492; 1 internal deletion; 2-residue insertion after 486; S362M, A363G, V365S +14 more |
Showing the 25 most-used of 68.
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 | 124 | 75.2% |
| tetrameric | 4 | 13 | 7.9% |
| dimeric | 2 | 9 | 5.5% |
| hexameric | 6 | 4 | 2.4% |
| 14-meric | 14 | 4 | 2.4% |
| trimeric | 3 | 3 | 1.8% |
| octameric | 8 | 2 | 1.2% |
| undecameric | 11 | 2 | 1.2% |
71 entries have the depositor's assembly corroborated by PISA, 92 carry the depositor's word alone and 2 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: 3L3L.
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 |
|---|---|---|---|
| Zinc finger, PARP-type | CATH 3.30.1740.10 | 26–116 | 20 |
| 1.10.20.130 | CATH | 226–291 | 2 |
| 2.20.25.630 | CATH | 292–351 | 2 |
| BRCT domain | CATH 3.40.50.10190 | 388–493 | 2 |
| Poly(ADP-ribose) polymerase, regulatory domain | CATH 1.20.142.10 | 670–799 | 60 |
| 3.90.228.10 | CATH | 800–1013 | 87 |
| WGR domain-like | SCOP2B 8074102 | 533–647 | 5 |
| WGR domain-like | SCOP2B 8039231 | 551–663 | 3 |
| Domain of poly(ADP-ribose) polymerase | SCOP2B 8036812 | 663–799 | 61 |
| Domain of poly(ADP-ribose) polymerase | SCOP2B 8037412 | 663–797 | 8 |
| ADP-ribosylation | SCOP2B 8037018 | 798–1012 | 8 |
| ADP-ribosylation | SCOP2B 8036814 | 801–1013 | 77 |
UHB7 entries
09L5 entries
78P4 entries
2YQ4 entries
3JD3 entries
RPB3 entries
DQV3 entries
CNA2 entries
P342 entries
FSU2 entries
D7N2 entries
L1S2 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| SO4 | ion | Sulfate Ion | 40 | 1.50 |
| ZN | ion | Zinc Ion | 26 | 1.70 |
| GOL | cryoprotectant | Glycerol | 22 | 1.70 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 18 | 1.50 |
| UHB | ligand | 2-[4-[(2s,3s,4r,5r)-5-(6-Aminopurin-9-Yl)-3,4-Bis(Oxidanyl)oxola | 7 | 2.70 |
| EDO | cryoprotectant | 1,2-Ethanediol | 6 | 1.74 |
| 09L | ligand | 4-(3-{[4-(Cyclopropylcarbonyl)piperazin-1-Yl]carbonyl}-4-Fluorob | 5 | 1.96 |
| 78P | ligand | (2r)-2-(7-Carbamoyl-1h-Benzimidazol-2-Yl)-2-Methylpyrrolidinium | 4 | 1.59 |
| 2YQ | ligand | (8s,9r)-5-Fluoro-8-(4-Fluorophenyl)-9-(1-Methyl-1h-1,2,4-Triazol | 4 | 2.06 |
| CIT | buffer | Citric Acid | 4 | 2.00 |
| 3JD | ligand | 2-{4-[(3s)-Piperidin-3-Yl]phenyl}-2h-Indazole-7-Carboxamide | 3 | 1.70 |
| RPB | ligand | Rucaparib | 3 | 2.10 |
| DQV | ligand | [(2r,3s,4r,5r)-5-(6-Amino-9h-Purin-9-Yl)-3,4-Dihydroxytetrahydro | 3 | 2.30 |
| CL | ion | Chloride Ion | 3 | 2.00 |
| CNA | ligand | Carba-Nicotinamide-Adenine-Dinucleotide | 2 | 2.25 |
| P34 | ligand | N~2~,n~2~-Dimethyl-N~1~-(6-Oxo-5,6-Dihydrophenanthridin-2-Yl)gly | 2 | 2.80 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 2 | 2.36 |
| FSU | ligand | 2-(3-Methoxypropyl)-3-Oxo-2,3-Dihydro-1h-Isoindole-4-Carboxamide | 2 | 1.65 |
| D7N | ligand | 2-[1-(4,4-Difluorocyclohexyl)-Piperidin-4-Yl]-6-Fluoro-3-Oxo-2,3 | 2 | 2.20 |
| 1PE | cryoprotectant | Pentaethylene Glycol | 2 | 1.80 |
Parsed from the free text 140 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 141
entries that recorded anything at all.
Median pH 7.5
(range 4.5 to 9.5).
165 entries carry a wwPDB validation report: 66 clean, 56 worth a check and 43 with something to explain. Median clashscore 4.53, median RSRZ outliers 2.5%, median R-free minus R-work 0.048. 162 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 153 | 1.50 | 116 | 100% |
| Gallus gallus | 9 | 2.10 | 8 | 36% |
| Mus musculus | 1 | 2.80 | 0 | 34% |
| Arabidopsis thaliana | 1 | 0 | 9% | |
| Rattus norvegicus | 1 | 0 | 10% |
1014 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 | High-Yield Production of Modified DNA Enables Structural Analysis of PARP2 Recognition of Nucleosomal Single-Strand Breaks. J.Mol.Biol. doi:10.1016/j.jmb.2026.169753 |
| 2026 | PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation. Nat Commun doi:10.1038/s41467-026-69375-3 |
| 2025 | Engaging an engineered PARP-2 catalytic domain mutant to solve the complex structures harboring approved drugs for structure analyses. Bioorg.Chem. doi:10.1016/j.bioorg.2025.108471 |
| 2025 | Employing a Highly Potent Fluorescence Probe to Discover a PARP-1/2 Binder and the Complex Structures Analysis. Chemmedchem doi:10.1002/cmdc.202500168 |
| 2024 | Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}- N -methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01725 |
| 2024 | Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks. Biochem.J. doi:10.1042/BCJ20230406 |
| 2024 | PARP enzyme de novo synthesis of protein-free poly(ADP-ribose). Mol.Cell doi:10.1016/j.molcel.2024.10.024 |
| 2024 | Discovery of Potent Isoindolinone Inhibitors that Target an Active Conformation of PARP1 Using DNA-Encoded Libraries. Chemmedchem doi:10.1002/cmdc.202400093 |
| 2023 | [1,2,4]Triazolo[3,4- b ]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes. J.Med.Chem. doi:10.1021/acs.jmedchem.2c01460 |
| 2023 | Discovery of Quinazoline-2,4(1 H ,3 H )-dione Derivatives Containing a Piperizinone Moiety as Potent PARP-1/2 Inhibitors─Design, Synthesis, In Vivo Antitumor Activity, and X-ray Crystal Structure Analysis. J.Med.Chem. doi:10.1021/acs.jmedchem.3c01152 |
| 2023 | Structural and biochemical analysis of the PARP1-homology region of PARP4/vault PARP. Nucleic Acids Res. doi:10.1093/nar/gkad1064 |
| 2022 | Captured snapshots of PARP1 in the active state reveal the mechanics of PARP1 allostery. Mol.Cell doi:10.1016/j.molcel.2022.06.011 |
| 2021 | Dynamics of the HD regulatory subdomain of PARP-1; substrate access and allostery in PARP activation and inhibition. Nucleic Acids Res. doi:10.1093/nar/gkab020 |
| 2021 | Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. J.Biol.Chem. doi:10.1074/jbc.RA120.016573 |
| 2021 | Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}- N -methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs. J.Med.Chem. doi:10.1021/acs.jmedchem.1c01012 |
| 2021 | HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones. Nat Commun doi:10.1038/s41467-021-21302-4 |
| 2021 | Activation of PARP2/ARTD2 by DNA damage induces conformational changes relieving enzyme autoinhibition. Nat Commun doi:10.1038/s41467-021-23800-x |
| 2021 | The BRCT domain of PARP1 binds intact DNA and mediates intrastrand transfer. Mol.Cell doi:10.1016/j.molcel.2021.11.014 |
| 2020 | Structural basis for allosteric PARP-1 retention on DNA breaks. Science doi:10.1126/science.aax6367 |
| 2020 | From PARP1 to TNKS2 Inhibition: A Structure-Based Approach. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.9b00654 |
| 2020 | Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development. J.Med.Chem. doi:10.1021/acs.jmedchem.0c01346 |
| 2020 | HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation. Nature doi:10.1038/s41586-020-2013-6 |
| 2020 | Bridging of DNA breaks activates PARP2-HPF1 to modify chromatin. Nature doi:10.1038/s41586-020-2725-7 |
| 2020 | Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1. Plos One doi:10.1371/journal.pone.0240932 |
| 2019 | Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity. J.Med.Chem. doi:10.1021/acs.jmedchem.8b01709 |
| 2019 | Discovery of Stereospecific PARP-1 Inhibitor Isoindolinone NMS-P515. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.8b00569 |
| 2018 | Structural basis for DNA break recognition by ARTD2/PARP2. Nucleic Acids Res. doi:10.1093/nar/gky927 |
| 2018 | Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors Eur J Med Chem doi:10.1016/j.ejmech.2018.01.018 |
| 2018 | NAD+analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains. Nat Commun doi:10.1038/s41467-018-03234-8 |
| 2017 | Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J. Med. Chem. doi:10.1021/acs.jmedchem.6b00990 |
| 2016 | Crystal structure-based discovery of a novel synthesized PARP1 inhibitor (OL-1) with apoptosis-inducing mechanisms in triple-negative breast cancer. Sci Rep doi:10.1038/s41598-016-0007-2 |
| 2015 | Discovery of 2-[1-(4,4-Difluorocyclohexyl)Piperidin-4-Yl]-6-Fluoro-3-Oxo-2,3-Dihydro-1H-Isoindole-4-Carboxamide (Nms-P118): A Potent, Orally Available and Highly Selective Parp- 1 Inhibitor for Cancer Therapy. J.Med.Chem. doi:10.1021/ACS.JMEDCHEM.5B00680 |
| 2015 | Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair. Mol.Cell doi:10.1016/j.molcel.2015.07.031 |
| 2015 | PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain. Mol.Cell doi:10.1016/j.molcel.2015.10.013 |
| 2015 | Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1. Mol.Cell doi:10.1016/j.molcel.2015.10.032 |
| 2014 | Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X14015088 |
| 2014 | Discovery and Structure-Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors. J.Med.Chem. doi:10.1021/jm5002502 |
| 2013 | PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3 Acs Chem.Biol. doi:10.1021/cb4002014 |
| 2013 | Chemical Probes to Study ADP-Ribosylation: Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3. J.Med.Chem. doi:10.1021/jm401394u |
| 2013 | Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2013.06.055 |