Homo sapiens · seed P56817 · 501 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P56817 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 2.40.70.10 SCOP 8036280 SCOP 8066379 RCSB 2ZJJ 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.
2ZJJ, 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.
67 distinct constructs across 456 entries. 455 polymer entities differ from the UniProt canonical sequence in some way, 1 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 |
|---|---|---|---|---|
| 51 | 402 | 1.35 | 6EQM | residues 46-447; E46G, T47P |
| 35 | 411 | 1.62 | 5I3V | residues 43-453; R56K, R57K |
| 31 | 406 | 1.70 | 2IQG | residues 56-461; R56M, T454R, L455S +6 more |
| 31 | 414 | 1.49 | 5HDZ | residues 41-454 |
| 22 | 415 | 1.78 | 5T1U | residues 46-460; L455H, M456H, T457H +3 more |
| 21 | 409 | 1.74 | 3ZMG | residues 46-454; K307A |
| 20 | 416 | 2.00 | 6JSE | residues 36-454; 1 internal deletion; A37S, P38H, L39M |
| 18 | 392 | 1.60 | 2VIJ | residues 61-452; N153Q, N172Q, N223Q +1 more |
| 18 | 442 | 1.25 | 7MYI | residues 13-454; G13M |
| 16 | 405 | 1.70 | 2B8L | residues 42-446; R42M, K136A, E138A |
| 13 | 433 | 1.59 | 4FGX | residues 12-454; 2 internal deletions; 3-residue insertion after 24; A14S, A19S, G21H +11 more |
| 13 | 455 | 1.79 | 3LPJ | residues 1-454; 1-residue insertion after 13; Q3S, A4M, L5T +7 more |
| 12 | 404 | 1.56 | 4FM7 | residues 58-461; T454R, L455S, M456H +5 more |
| 11 | 386 | 1.31 | 7D5B | residues 75-460 |
| 11 | 402 | 2.10 | 2OHQ | residues 45-446; R56K, R57K |
| 9 | 390 | 1.72 | 3CIB | residues 58-447 |
| 8 | 389 | 1.86 | 2G94 | residues 58-446 |
| 6 | 408 | 2.00 | 3MSK | residues 46-453; E46G, T47P |
| 5 | 97 | 1.55 | 6QCB | residues 65-161 |
| 5 | 386 | 1.90 | 3ZKG | residues 75-460; E331A |
| 5 | 388 | 2.00 | 4GID | residues 59-446 |
| 5 | 390 | 1.52 | 5F01 | residues 57-446; K307A |
| 5 | 395 | 1.50 | 2QP8 | residues 53-447; E53A, P54A |
| 5 | 395 | 1.70 | 3KMX | residues 53-447 |
| 5 | 411 | 1.85 | 2ZHV | residues 44-454; P44M |
Showing the 25 most-used of 67.
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 | 399 | 87.5% |
| dimeric | 2 | 48 | 10.5% |
| trimeric | 3 | 4 | 0.9% |
| tetrameric | 4 | 4 | 0.9% |
| hexameric | 6 | 1 | 0.2% |
325 entries have the depositor's assembly corroborated by PISA, 121 carry the depositor's word alone and 10 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 29 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1LYB, 1LYW, 1XN3, 2EWY, 3FKT, 3KMX, 3KMY, 3LPI, 3LPJ, 3LPK, 3OHF, 3OHH, 4FCO, 4FGX, 4FS4, 4HZT, 4I0D, 4I0E, 4I0F, 4I0G.
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 |
|---|---|---|---|
| Acid Proteases | CATH 2.40.70.10 | 96–228 | 861 |
| Acid proteases | SCOP2B 8036280 | 60–446 | 425 |
| Acid proteases | SCOP2B 8066379 | 62–443 | 18 |
URE8 entries
NAG7 entries
B3P4 entries
WZV4 entries
5HA3 entries
66F3 entries
AXQ2 entries
AXF2 entries
CS52 entries
H242 entries
VG52 entries
BSD2 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| GOL | cryoprotectant | Glycerol | 85 | 1.25 |
| IOD | ion | Iodide Ion | 77 | 1.62 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 54 | 1.38 |
| SO4 | ion | Sulfate Ion | 40 | 1.29 |
| NA | ion | Sodium Ion | 28 | 1.31 |
| TLA | buffer | L(+)-Tartaric Acid | 27 | 1.50 |
| ZN | ion | Zinc Ion | 21 | 1.56 |
| CL | ion | Chloride Ion | 16 | 1.31 |
| TAR | buffer | D(-)-Tartaric Acid | 13 | 1.50 |
| EDO | cryoprotectant | 1,2-Ethanediol | 13 | 1.31 |
| ACT | cryoprotectant | Acetate Ion | 12 | 1.52 |
| NI | ion | Nickel (Ii) Ion | 12 | 1.70 |
| URE | ligand | Urea | 8 | 1.59 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 8 | 1.59 |
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 7 | 1.80 |
| PO4 | ion | Phosphate Ion | 4 | 1.95 |
| B3P | ligand | 2-[3-(2-Hydroxy-1,1-Dihydroxymethyl-Ethylamino)-Propylamino]-2-H | 4 | 1.51 |
| WZV | ligand | 5-(2,2,2-Trifluoro-Ethoxy)-Pyridine-2-Carboxylic Acid [3-((S)-2- | 4 | 2.00 |
| 5HA | ligand | N-[(1s,2r)-1-Benzyl-3-(Cyclopropylamino)-2-Hydroxypropyl]-5-[Met | 3 | 1.60 |
| 66F | ligand | N-{3-[(5r)-3-Amino-2,5-Dimethyl-1,1-Dioxido-5,6-Dihydro-2h-1,2,4 | 3 | 1.31 |
Parsed from the free text 439 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 449
entries that recorded anything at all.
Median pH 6.5
(range 3.2 to 8.5).
456 entries carry a wwPDB validation report: 140 clean, 211 worth a check and 105 with something to explain. Median clashscore 4.35, median RSRZ outliers 5.26%, median R-free minus R-work 0.036. 426 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 456 | 1.25 | 427 | 100% |
501 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 |
|---|---|
| 2021 | Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.1c00489 |
| 2021 | Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective beta-Secretase (BACE1) Inhibitors over BACE2. J.Med.Chem. doi:10.1021/acs.jmedchem.0c01858 |
| 2021 | JNJ-67569762, A 2-Aminotetrahydropyridine-Based Selective BACE1 Inhibitor Targeting the S3 Pocket: From Discovery to Clinical Candidate. J.Med.Chem. doi:10.1021/acs.jmedchem.1c00935 |
| 2021 | Discovery of Extremely Selective Fused Pyridine-Derived beta-Site Amyloid Precursor Protein-Cleaving Enzyme (BACE1) Inhibitors with High In Vivo Efficacy through 10s Loop Interactions. J.Med.Chem. doi:10.1021/acs.jmedchem.1c00359 |
| 2021 | Synthesis of the Potent, Selective, and Efficacious beta-Secretase (BACE1) Inhibitor NB-360. J.Med.Chem. doi:10.1021/acs.jmedchem.0c02143 |
| 2021 | A Structure-Based Discovery Platform for BACE2 and the Development of Selective BACE Inhibitors. Acs Chem Neurosci doi:10.1021/acschemneuro.0c00629 |
| 2021 | Balancing potency and basicity by incorporating fluoropyridine moieties: Discovery of a 1-amino-3,4-dihydro-2,6-naphthyridine BACE1 inhibitor that affords robust and sustained central A beta reduction. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2021.113270 |
| 2021 | Discovery of Atabecestat (JNJ-54861911): A Thiazine-Based beta-Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor Advanced to the Phase 2b/3 EARLY Clinical Trial. J.Med.Chem. doi:10.1021/acs.jmedchem.0c01917 |
| 2020 | Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints. Bioorg.Med.Chem. doi:10.1016/j.bmc.2019.115194 |
| 2020 | Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure-Activity Relationship and Binding Mode Analysis. J.Med.Chem. doi:10.1021/acs.jmedchem.9b01351 |
| 2020 | Discovery of AM-6494: A Potent and Orally Efficacious beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor with in Vivo Selectivity over BACE2. J.Med.Chem. doi:10.1021/acs.jmedchem.9b01034 |
| 2020 | The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2020.127240 |
| 2020 | Discovery and Chemical Development of JNJ-50138803, a Clinical Candidate BACE1 Inhibitor Acs Symp.Ser. doi:10.1021/bk-2018-1307.ch004 |
| 2020 | D3R grand challenge 4: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies. J.Comput.Aided Mol.Des. doi:10.1007/s10822-020-00289-y |
| 2019 | Structure-Based Design of Selective beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors: Targeting the Flap to Gain Selectivity over BACE2. J.Med.Chem. doi:10.1021/acs.jmedchem.9b00309 |
| 2019 | Evaluation of a Series of beta-Secretase 1 Inhibitors Containing Novel Heteroaryl-Fused-Piperazine Amidine Warheads. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.9b00181 |
| 2019 | Development of an Efficient Enzyme Production and Structure-Based Discovery Platform for BACE1 Inhibitors. Biochemistry doi:10.1021/acs.biochem.9b00714 |
| 2019 | Trifluoromethyl Dihydrothiazine-Based beta-Secretase (BACE1) Inhibitors with Robust Central beta-Amyloid Reduction and Minimal Covalent Binding Burden. Chemmedchem doi:10.1002/cmdc.201900478 |
| 2019 | Discovery of an Extremely Potent Thiazine-Based beta-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose. J.Med.Chem. doi:10.1021/acs.jmedchem.9b01140 |
| 2018 | The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease. EMBO Mol Med doi:10.15252/emmm.201809316 |
| 2018 | Toward beta-Secretase-1 Inhibitors with Improved Isoform Selectivity. J. Med. Chem. doi:10.1021/acs.jmedchem.7b01716 |
| 2018 | Discovery of amino-1,4-oxazines as potent BACE-1 inhibitors. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2018.05.003 |
| 2018 | qFit-ligand Reveals Widespread Conformational Heterogeneity of Drug-Like Molecules in X-Ray Electron Density Maps. J. Med. Chem. doi:10.1021/acs.jmedchem.8b01292 |
| 2018 | Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine beta-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2018.01.056 |
| 2018 | Discovery of Potent and Centrally Active 6-Substituted 5-Fluoro-1,3-dihydro-oxazine beta-Secretase (BACE1) Inhibitors via Active Conformation Stabilization J. Med. Chem. doi:10.1021/acs.jmedchem.8b00011 |
| 2018 | Rational Design of Novel 1,3-Oxazine Based beta-Secretase (BACE1) Inhibitors: Incorporation of a Double Bond To Reduce P-gp Efflux Leading to Robust A beta Reduction in the Brain J. Med. Chem. doi:10.1021/acs.jmedchem.8b00002 |
| 2018 | Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2018.06.045 |
| 2017 | Optimization of Hydroxyethylamine Transition State Isosteres as Aspartic Protease Inhibitors by Exploiting Conformational Preferences. J. Med. Chem. doi:10.1021/acs.jmedchem.7b01304 |
| 2017 | Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality. J. Med. Chem. doi:10.1021/acs.jmedchem.6b01451 |
| 2017 | Potent and Selective BACE-1 Peptide Inhibitors Lower Brain A beta Levels Mediated by Brain Shuttle Transport. EBioMedicine doi:10.1016/j.ebiom.2017.09.004 |
| 2017 | Development of 2-aminooxazoline 3-azaxanthene beta-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D. Medchemcomm doi:10.1039/c7md00106a |
| 2017 | Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1'-P2' ligands. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2017.04.011 |
| 2016 | Structure-Based Design of an Iminoheterocyclic beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central A beta in Nonhuman Primates. J.Med.Chem. doi:10.1021/acs.jmedchem.5b01995 |
| 2016 | Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease. J. Med. Chem. doi:10.1021/acs.jmedchem.6b00307 |
| 2016 | A Real-World Perspective on Molecular Design. J.Med.Chem. doi:10.1021/acs.jmedchem.5b01875 |
| 2016 | Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of beta-Secretase. J.Med.Chem. doi:10.1021/acs.jmedchem.5b01917 |
| 2016 | Targeting the BACE1 Active Site Flap Leads to a Potent Inhibitor That Elicits Robust Brain A beta Reduction in Rodents. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5b00432 |
| 2016 | Discovery of S3-Truncated, C-6 Heteroaryl Substituted Aminothiazine beta-Site APP Cleaving Enzyme-1 (BACE1) Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.6b01012 |
| 2016 | Design of Potent and Highly Selective Inhibitors for Human beta-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes. Chem Sci doi:10.1039/C5SC03718B |
| 2016 | Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2016.10.055 |