Homo sapiens · seed P37840 · 140 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P37840 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 1.10.287.700 SCOP 8044121 SCOP 8058187 RCSB 9JE2 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.
9JE2, 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.
45 distinct constructs across 234 entries. 74 polymer entities differ from the UniProt canonical sequence in some way, 0 carry a recognised expression tag and 2 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 |
|---|---|---|---|---|
| 155 | 140 | 1.93 | 9EUU | matches the canonical sequence |
| 10 | 140 | 2.31 | 8PJO | E46K |
| 8 | 140 | 2.39 | 9JC3 | G51D, A53T |
| 5 | 140 | 2.21 | 9CKK | A53T |
| 5 | 140 | 2.60 | 9K23 | matches the canonical sequence |
| 3 | 55 | 3.10 | 8ZLO | residues 45-99; E46K |
| 3 | 64 | 2.87 | 9W08 | residues 37-100 |
| 3 | 140 | 2.90 | 9O9K | H50Q |
| 2 | 62 | 3.40 | 9JKE | residues 37-98; G51D, A53T, K58W |
| 2 | 63 | 2.85 | 9JI8 | residues 37-99 |
| 2 | 99 | 2.90 | 8ZMY | residues 1-98 |
| 2 | 140 | 2.30 | 9O9J | G51D |
| 2 | 140 | 3.36 | 9KAL | G51D, A53T, E57A |
| 1 | 20 | 1.72 | 8ZVY | residues 121-140 |
| 1 | 22 | residues 35-56 | ||
| 1 | 27 | residues 1-26 | ||
| 1 | 61 | 3.80 | 9RZF | residues 37-97; N87S |
| 1 | 63 | 3.03 | 9W07 | residues 36-98; Y39E, K45G, K58G |
| 1 | 63 | 3.32 | 9JDK | residues 37-99; G51D, A53T |
| 1 | 65 | 2.70 | 7WO0 | residues 35-99; A53T |
| 1 | 65 | 3.40 | 7WNZ | residues 36-100; A53T |
| 1 | 65 | 3.43 | 9TPT | residues 36-100; E83Q |
| 1 | 67 | 3.18 | 10XU | residues 35-101 |
| 1 | 69 | 3.30 | 9V7C | residues 32-101; 1 internal deletion; L100G, G101A |
| 1 | 90 | 4.80 | 8GF7 | residues 7-96 |
Showing the 25 most-used of 45.
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 |
|---|---|---|---|
| hexameric | 6 | 73 | 31.2% |
| decameric | 10 | 63 | 26.9% |
| dodecameric | 12 | 32 | 13.7% |
| monomeric | 1 | 10 | 4.3% |
| trimeric | 3 | 10 | 4.3% |
| pentadecameric | 15 | 10 | 4.3% |
| octameric | 8 | 8 | 3.4% |
| pentameric | 5 | 5 | 2.1% |
74 entries have the depositor's assembly corroborated by PISA, 155 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.
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 |
|---|---|---|---|
| Helix hairpin bin | CATH 1.10.287.700 | 1–140 | 2 |
| Synuclein | SCOP2B 8044121 | 1–140 | 3 |
| Type 2 solute binding protein-like | SCOP2B 8058187 | 34–140 | 2 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| A1BGB | ligand | 2-(4-Benzyl-1-Oxophthalazin-2(1h)-Yl)-N-(2,6-Dimethylphenyl)acet | 4 | 2.80 |
| A1EFL | ligand | (2~{R})-1-Fluoranyl-3-[[2-[(~{E})-2-[5-[6-(Methylamino)pyridin-3 | 4 | 2.60 |
| CU | ion | Copper (Ii) Ion | 3 | |
| 1KI | ligand | 2-Bromanyl-4-[(~{E})-2-[6-[2-(2-Fluoranylethoxy)ethyl-Methyl-Ami | 3 | 2.60 |
| TFX | ligand | 2-[4-(Dimethylamino)phenyl]-3,6-Dimethyl-1,3-Benzothiazol-3-Ium | 3 | 2.90 |
| IZV | ligand | 2-[4-(Methylamino)phenyl]-1,3-Benzothiazol-6-Ol | 3 | 2.80 |
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 3 | 3.10 |
| CL | ion | Chloride Ion | 3 | 1.72 |
| SO4 | ion | Sulfate Ion | 2 | 1.30 |
| GOL | cryoprotectant | Glycerol | 2 | 1.30 |
| V79 | ligand | Copper;trisodium;18-(2-Carboxylatoethyl)-20-(Carboxylatomethyl)- | 2 | 2.50 |
| IZ8 | ligand | 4-Azanyl-6-[[4-[4-[(~{E})-(8-Azanyl-1-Oxidanyl-5,7-Disulfo-Napht | 2 | 2.60 |
| IZM | ligand | 5-[(~{E})-2-(6-Methoxy-1,3-Benzoxazol-2-Yl)ethenyl]-~{N},~{N}-Di | 1 | 2.80 |
| 59P | ligand | 3,3'-{[1,1'-Biphenyl]-4,4'-Diylbis[(E)-Diazene-2,1-Diyl]}bis(4-A | 1 | 3.00 |
| 3LS | ligand | 3''',4'-Bis(Carboxymethyl)-2,2':5',2'':5'',2''':5''',2''''-Quinq | 1 | 2.70 |
| Y9W | ligand | 2-[(~{E})-4-[6-(Methylamino)pyridin-3-Yl]but-1-En-3-Ynyl]-1,3-Be | 1 | 3.00 |
| KDH | ligand | (2r,3r)-5,7-Dihydroxy-2-(3,4,5-Trihydroxyphenyl)-3,4-Dihydro-2h- | 1 | 3.10 |
| A1L13 | ligand | ~{N},~{N}-Dimethyl-4-(6-Methyl-1,3-Benzothiazol-2-Yl)aniline | 1 | 3.40 |
| 7TT | ligand | Tetraphosphate | 1 | 3.10 |
| A1EFK | ligand | 2-[(4~{E})-4-[(~{E})-3-(3-Methyl-1,3-Benzothiazol-2-Yl)prop-2-En | 1 | 2.90 |
Parsed from the free text 4 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 4
entries that recorded anything at all.
Median pH 8.0
(range 8.0 to 9.0).
230 entries carry a wwPDB validation report: 194 clean, 28 worth a check and 8 with something to explain. Median clashscore 8.55, median RSRZ outliers 3.85%, median R-free minus R-work 0.043. 230 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 226 | 1.72 | 40 | 100% |
| Mus musculus | 5 | 2.60 | 0 | 100% |
| Escherichia coli | 2 | 1.30 | 0 | 35% |
| Unknown | 1 | 0 | 100% |
140 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 | Formation of Condition-Dependent Alpha-Synuclein Fibril Strain in Artificial Cerebrospinal Fluid. Adv Sci doi:10.1002/advs.202505228 |
| 2026 | Stochastic misfolding drives the emergence of distinct alpha-synuclein strains. Neuron doi:10.1016/j.neuron.2026.01.014 |
| 2025 | Structural and functional insights into the nuclear role of Parkinson's disease-associated alpha-synuclein as a histone chaperone. Commun Biol doi:10.1038/s42003-025-08138-0 |
| 2025 | Synthetic alpha-synuclein fibrils replicate in mice causing MSA-like pathology. Nature doi:10.1038/s41586-025-09698-1 |
| 2025 | High-resolution Cryo-EM Structure Determination of a-Synuclein-A Prototypical Amyloid Fibril. Bio Protoc doi:10.21769/BioProtoc.5171 |
| 2025 | Lewy-MSA hybrid fold drives distinct neuronal alpha-synuclein pathology. Commun Biol doi:10.1038/s42003-025-08355-7 |
| 2025 | Fibril fuzzy coat is important for alpha-synuclein pathological transmission activity. Neuron doi:10.1016/j.neuron.2025.03.019 |
| 2025 | Structural basis of a distinct alpha-synuclein strain that promotes tau inclusion in neurons. J.Biol.Chem. doi:10.1016/j.jbc.2025.108351 |
| 2025 | Structural insight into binding of novel PET tracer MODAG-005 to lipidic alpha-Synuclein fibrils Biorxiv doi:10.1101/2025.04.21.649837 |
| 2025 | A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features. Mol Neurodegener doi:10.1186/s13024-025-00889-y |
| 2025 | Leveraging bioorthogonal conjugation for alpha synuclein fibril surveillance. Biorxiv doi:10.1101/2025.09.12.675751 |
| 2025 | A Novel alpha-Synuclein K58N Missense Variant in a Patient with Parkinson's Disease. Mov Disord doi:10.1002/mds.70030 |
| 2025 | ATP Hydrolysis by alpha-Synuclein Amyloids is Mediated by Enclosing beta-Strand. Adv Sci doi:10.1002/advs.202508441 |
| 2025 | Single-Molecule Insight Into alpha-Synuclein Fibril Structure and Mechanics Modulated by Chemical Compounds. Adv Sci doi:10.1002/advs.202416721 |
| 2025 | Seed amplification of MSA alpha-synuclein aggregates preserves the biological and structural properties of brain-derived aggregates. Nat Commun doi:10.1038/s41467-025-66146-4 |
| 2025 | Stepwise recruitment of chaperone Hsc70 by DNAJB1 produces ordered arrays primed for bursts of amyloid fibril disassembly. Commun Biol doi:10.1038/s42003-025-07906-2 |
| 2025 | Cryo-EM structure of a novel alpha-synuclein filament subtype from multiple system atrophy. Febs Lett. doi:10.1002/1873-3468.15048 |
| 2025 | Identical Seeding Characteristics and Cryo-EM Filament Structures in FTLD-Synuclein and Typical Multiple System Atrophy. Neuropathol Appl Neurobiol doi:10.1111/nan.70013 |
| 2025 | Development of Nanomolar Affinity Miniprotein Inhibitors Targeting alpha-Synuclein Aggregation as Promising Therapeutic Agents for Parkinson's Disease Ccs Chem doi:10.31635/ccschem.025.202505587 |
| 2024 | In cell NMR reveals cells selectively amplify and structurally remodel amyloid fibrils. Biorxiv doi:10.1101/2024.09.09.612142 |
| 2024 | On the pH-dependence of alpha-synuclein amyloid polymorphism and the role of secondary nucleation in seed-based amyloid propagation. Elife doi:10.7554/eLife.93562 |
| 2024 | Residues 2 to 7 of alpha-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2315006121 |
| 2024 | Phosphorylation and O-GlcNAcylation at the same alpha-synuclein site generate distinct fibril structures. Nat Commun doi:10.1038/s41467-024-46898-1 |
| 2024 | Binding adaptability of chemical ligands to polymorphic alpha-synuclein amyloid fibrils. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2321633121 |
| 2024 | Different charged biopolymers induce alpha-synuclein to form fibrils with distinct structures. J.Biol.Chem. doi:10.1016/j.jbc.2024.107862 |
| 2024 | Mouse alpha-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases. Sci Adv doi:10.1126/sciadv.adq3539 |
| 2024 | Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson's disease. Brain doi:10.1093/brain/awae061 |
| 2024 | Structure-Toxicity Relationship in Intermediate Fibrils from alpha-Synuclein Condensates. J.Am.Chem.Soc. doi:10.1021/jacs.3c14703 |
| 2024 | O-GlcNAc forces an alpha-synuclein amyloid strain with notably diminished seeding and pathology. Nat.Chem.Biol. doi:10.1038/s41589-024-01551-2 |
| 2024 | Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue. Nat Commun doi:10.1038/s41467-024-46832-5 |
| 2023 | New SNCA mutation and structures of alpha-synuclein filaments from juvenile-onset synucleinopathy. Acta Neuropathol doi:10.1007/s00401-023-02550-8 |
| 2023 | Conformational change of alpha-synuclein fibrils in cerebrospinal fluid from different clinical phases of Parkinson's disease. Structure doi:10.1016/j.str.2022.11.013 |
| 2023 | Structural Insights of Fe3+ Induced alpha-synuclein Fibrillation in Parkinson' Disease J.Mol.Biol. doi:10.1016/j.jmb.2022.167680 |
| 2023 | Conformational Dynamics of an alpha-Synuclein Fibril upon Receptor Binding Revealed by Insensitive Nuclei Enhanced by Polarization Transfer-Based Solid-State Nuclear Magnetic Resonance and Cryo-Electron Microscopy. J.Am.Chem.Soc. doi:10.1021/jacs.2c10854 |
| 2023 | Cryo-EM structure of amyloid fibril formed by alpha-synuclein hereditary A53E mutation reveals a distinct protofilament interface. J.Biol.Chem. doi:10.1016/j.jbc.2023.104566 |
| 2023 | An N-terminal alpha-Synuclein fragment binds lipid vesicles to modulate lipid induced aggregation Cell Rep Phys Sci |
| 2023 | High-resolution structural information of membrane-bound alpha-synuclein provides insight into the MoA of the anti-Parkinson drug UCB0599 Proc. Natl. Acad. Sci. U. S. A. doi:10.1073/pnas.2201910120 |
| 2023 | Structural and Dynamic Insights into -Synuclein Dimer Conformations doi:10.1016/j.str.2023.01.011 |
| 2022 | Structures of alpha-synuclein filaments from human brains with Lewy pathology. Nature doi:10.1038/s41586-022-05319-3 |
| 2022 | The 3D structure of lipidic fibrils of alpha-synuclein. Nat Commun doi:10.1038/s41467-022-34552-7 |