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Entry version 223 (08 May 2019)
Sequence version 1 (01 Oct 1994)
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Protein

Alpha-synuclein

Gene

SNCA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). Mechanistically, acts by increasing local Ca2+ release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282). Plays also a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi2CopperCurated1
Metal bindingi50CopperCurated1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

LigandCopper, Metal-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-977225 Amyloid fiber formation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P37840

SIGNOR Signaling Network Open Resource

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SIGNORi
P37840

Protein family/group databases

Transport Classification Database

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TCDBi
1.C.77.1.1 the synuclein (synuclein) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Alpha-synuclein
Alternative name(s):
Non-A beta component of AD amyloid
Non-A4 component of amyloid precursor
Short name:
NACP
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SNCA
Synonyms:NACP, PARK1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:11138 SNCA

Online Mendelian Inheritance in Man (OMIM)

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MIMi
163890 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P37840

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Amyloid, Cell junction, Cytoplasm, Membrane, Nucleus, Secreted, Synapse

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.
Parkinson disease 1, autosomal dominant (PARK1)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
See also OMIM:168601
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00795730A → P in PARK1; no effect on oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs104893878EnsemblClinVar.1
Natural variantiVAR_02270346E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes; increases oligomerization. 3 PublicationsCorresponds to variant dbSNP:rs104893875EnsemblClinVar.1
Natural variantiVAR_07017150H → Q in PARK1; no effect on protein structure; no effect on phosphorylation of the protein; no effect on membrane- and lipid-binding; increases oligomerization; increases fibril formation; increases secretion of the protein; impairs copper-binding. 4 PublicationsCorresponds to variant dbSNP:rs201106962EnsemblClinVar.1
Natural variantiVAR_00745453A → T in PARK1; no effect on osmotic stress-induced phosphorylation; increases oligomerization. 3 PublicationsCorresponds to variant dbSNP:rs104893877EnsemblClinVar.1
Parkinson disease 4, autosomal dominant (PARK4)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
See also OMIM:605543
Dementia Lewy body (DLB)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
See also OMIM:127750
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02270346E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes; increases oligomerization. 3 PublicationsCorresponds to variant dbSNP:rs104893875EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi2D → A: Impairs copper-binding. 1 Publication1
Mutagenesisi35E → K: No effect on oligomerization. 1 Publication1
Mutagenesisi39Y → F: No effect on osmotic stress-induced phosphorylation. 1 Publication1
Mutagenesisi50H → A: Impairs copper-binding. 1 Publication1
Mutagenesisi57E → K: Increases oligomerization. 1 Publication1
Mutagenesisi67 – 71Missing : Reduces polymerization into amyloid fibrils. 1 Publication5
Mutagenesisi71 – 82Missing : Impairs polymerization into amyloid fibrils. 1 PublicationAdd BLAST12
Mutagenesisi76 – 77Missing : Impairs polymerization into amyloid fibrils. 1 Publication2
Mutagenesisi76Missing : Does not affect polymerization into amyloid fibrils. 1
Mutagenesisi77Missing : Does not affect polymerization into amyloid fibrils. 1 Publication1
Mutagenesisi78Missing : Does not affect polymerization into amyloid fibrils. 1 Publication1
Mutagenesisi85 – 94Missing : Reduces polymerization into amyloid fibrils. 1 Publication10
Mutagenesisi125Y → F: Abolishes osmotic stress-induced phosphorylation. 1 Publication1
Mutagenesisi133Y → F: No effect on osmotic stress-induced phosphorylation. 1 Publication1
Mutagenesisi136Y → F: No effect on osmotic stress-induced phosphorylation. 1 Publication1

Keywords - Diseasei

Alzheimer disease, Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNET

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DisGeNETi
6622

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
SNCA

MalaCards human disease database

More...
MalaCardsi
SNCA
MIMi127750 phenotype
168600 phenotype
168601 phenotype
605543 phenotype

Open Targets

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OpenTargetsi
ENSG00000145335

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
411602 Hereditary late-onset Parkinson disease
1648 NON RARE IN EUROPE: Dementia with Lewy body
171695 Parkinsonian-pyramidal syndrome
2828 Young-onset Parkinson disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA35986

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL6152

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
SNCA

Domain mapping of disease mutations (DMDM)

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DMDMi
586067

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001840221 – 140Alpha-synucleinAdd BLAST140

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1N-acetylmethionine1 Publication1
Modified residuei87Phosphoserine1 Publication1
Modified residuei125Phosphotyrosine; by FYN2 Publications1
Modified residuei129Phosphoserine; by BARK1, PLK2, CK2, CK1 and GRK53 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress.6 Publications
Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.
Ubiquitinated. The predominant conjugate is the diubiquitinated form (By similarity).By similarity
Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P37840

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P37840

MaxQB - The MaxQuant DataBase

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MaxQBi
P37840

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P37840

PeptideAtlas

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PeptideAtlasi
P37840

PRoteomics IDEntifications database

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PRIDEi
P37840

ProteomicsDB human proteome resource

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ProteomicsDBi
55279
55280 [P37840-2]
55281 [P37840-3]

Consortium for Top Down Proteomics

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TopDownProteomicsi
P37840-1 [P37840-1]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P37840

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P37840

SwissPalm database of S-palmitoylation events

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SwissPalmi
P37840

Miscellaneous databases

CutDB - Proteolytic event database

More...
PMAP-CutDBi
P37840

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in presynaptic terminals in the central nervous system. Expressed principally in brain.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000145335 Expressed in 237 organ(s), highest expression level in bone marrow

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P37840 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P37840 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB010877
HPA005459

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Soluble monomer. Homotetramer (PubMed:21841800). A dynamic intracellular population of tetramers and monomers coexists normally and the tetramer plays an essential role in maintaining homeostasis (PubMed:21841800). Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones. Interacts (via N-terminus) with synphilin-1/SNCAIP; this interaction promotes formation of SNCA inclusions in the cytoplasm (PubMed:19762560). Interacts with CALM1 (PubMed:23607618). Interacts with STXBP1; this interaction controls SNCA self-replicating aggregation (PubMed:27597756). Interacts with SNARE components VAMP2 and SNAP25; these interactions allows SNARE complex assembly and integrity (PubMed:20798282). Interacts with RPH3A and RAB3A (PubMed:15207266).By similarity6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
112506, 474 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P37840

Database of interacting proteins

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DIPi
DIP-35354N

Protein interaction database and analysis system

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IntActi
P37840, 265 interactors

Molecular INTeraction database

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MINTi
P37840

STRING: functional protein association networks

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STRINGi
9606.ENSP00000338345

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P37840

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1140
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XQ8NMR-A1-140[»]
2JN5NMR-A1-12[»]
2KKWNMR-A1-140[»]
2M55NMR-B1-19[»]
2N0ANMR-A/B/C/D/E/F/G/H/I/J1-140[»]
2X6MX-ray1.62B132-140[»]
3Q25X-ray1.90A1-19[»]
3Q26X-ray1.54A10-42[»]
3Q27X-ray1.30A32-57[»]
3Q28X-ray1.60A58-79[»]
3Q29X-ray2.30A/C1-19[»]
4BXLNMR-C35-56[»]
4R0UX-ray1.38A72-78[»]
4R0WX-ray1.50A70-76[»]
4RIKX-ray1.85A69-77[»]
4RILelectron microscopy1.43A68-78[»]
4ZNNelectron microscopy1.41A47-56[»]
5CRWX-ray1.60B31-41[»]
6A6Belectron microscopy3.07A/B/C/D/E/F/G/H/I/J/K/L37-99[»]
6CU7electron microscopy3.50A/B/C/D/E/F/G/H/I/J1-140[»]
6CU8electron microscopy3.60A/B/C/D/E/F/G/H/I/J1-140[»]
6FLTelectron microscopy3.42A/B/C/D/E/F/G/H/I/J1-121[»]
6H6Belectron microscopy3.40A/B/C/D/E/F/G/H/I/J1-121[»]

Database of protein disorder

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DisProti
DP00070

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P37840

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P37840

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati20 – 301Add BLAST11
Repeati31 – 412Add BLAST11
Repeati42 – 563; approximateAdd BLAST15
Repeati57 – 674Add BLAST11

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni20 – 674 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V-X(4)Add BLAST48

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The 'non A-beta component of Alzheimer disease amyloid plaque' domain (NAC domain) is involved in fibrils formation. The middle hydrophobic region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments.1 Publication

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the synuclein family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IWI2 Eukaryota
ENOG4111TDZ LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00950000183175

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000008691

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P37840

KEGG Orthology (KO)

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KOi
K04528

Identification of Orthologs from Complete Genome Data

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OMAi
SEAYEMP

Database of Orthologous Groups

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OrthoDBi
716326at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P37840

TreeFam database of animal gene trees

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TreeFami
TF332776

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR001058 Synuclein
IPR002460 Synuclein_alpha

The PANTHER Classification System

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PANTHERi
PTHR13820 PTHR13820, 1 hit
PTHR13820:SF5 PTHR13820:SF5, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF01387 Synuclein, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR01212 ASYNUCLEIN
PR01211 SYNUCLEIN

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P37840-1) [UniParc]FASTAAdd to basket
Also known as: NACP140

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH
60 70 80 90 100
GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL
110 120 130 140
GKNEEGAPQE GILEDMPVDP DNEAYEMPSE EGYQDYEPEA
Length:140
Mass (Da):14,460
Last modified:October 1, 1994 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i6BB2F12128931663
GO
Isoform 2-4 (identifier: P37840-2) [UniParc]FASTAAdd to basket
Also known as: NACP112

The sequence of this isoform differs from the canonical sequence as follows:
     103-130: Missing.

Show »
Length:112
Mass (Da):11,372
Checksum:i16EA234777EFA89E
GO
Isoform 2-5 (identifier: P37840-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     41-54: Missing.

Show »
Length:126
Mass (Da):13,109
Checksum:i0F87D9A60E831E02
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EPV7E7EPV7_HUMAN
Alpha-synuclein
SNCA
115Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H6UYS7H6UYS7_HUMAN
Alpha-synuclein
SNCA
98Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D6RA31D6RA31_HUMAN
Alpha-synuclein
SNCA
66Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00795730A → P in PARK1; no effect on oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs104893878EnsemblClinVar.1
Natural variantiVAR_02270346E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes; increases oligomerization. 3 PublicationsCorresponds to variant dbSNP:rs104893875EnsemblClinVar.1
Natural variantiVAR_07017150H → Q in PARK1; no effect on protein structure; no effect on phosphorylation of the protein; no effect on membrane- and lipid-binding; increases oligomerization; increases fibril formation; increases secretion of the protein; impairs copper-binding. 4 PublicationsCorresponds to variant dbSNP:rs201106962EnsemblClinVar.1
Natural variantiVAR_00745453A → T in PARK1; no effect on osmotic stress-induced phosphorylation; increases oligomerization. 3 PublicationsCorresponds to variant dbSNP:rs104893877EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_00636341 – 54Missing in isoform 2-5. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_006364103 – 130Missing in isoform 2-4. 2 PublicationsAdd BLAST28

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
L08850 mRNA Translation: AAA16117.1
L36674 mRNA Translation: AAA98493.1
L36675 mRNA Translation: AAA98487.1
D31839 mRNA Translation: BAA06625.1
U46901
, U46897, U46898, U46899 Genomic DNA Translation: AAC02114.1
AF163864 Genomic DNA Translation: AAG30302.1
AF163864 Genomic DNA Translation: AAG30303.1
AY049786 mRNA Translation: AAL15443.1
AK290169 mRNA Translation: BAF82858.1
CR457058 mRNA Translation: CAG33339.1
DQ088379 Genomic DNA Translation: AAY88735.1
CH471057 Genomic DNA Translation: EAX06036.1
BC013293 mRNA Translation: AAH13293.1
BC108275 mRNA Translation: AAI08276.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS3634.1 [P37840-1]
CCDS43252.1 [P37840-2]

Protein sequence database of the Protein Information Resource

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PIRi
A49669
S56746

NCBI Reference Sequences

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RefSeqi
NP_000336.1, NM_000345.3 [P37840-1]
NP_001139526.1, NM_001146054.1 [P37840-1]
NP_001139527.1, NM_001146055.1 [P37840-1]
NP_009292.1, NM_007308.2 [P37840-2]
XP_011530510.1, XM_011532208.2 [P37840-1]
XP_016864051.1, XM_017008562.1 [P37840-1]
XP_016864052.1, XM_017008563.1 [P37840-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000336904; ENSP00000338345; ENSG00000145335 [P37840-1]
ENST00000345009; ENSP00000343683; ENSG00000145335 [P37840-2]
ENST00000394986; ENSP00000378437; ENSG00000145335 [P37840-1]
ENST00000394989; ENSP00000378440; ENSG00000145335 [P37840-3]
ENST00000394991; ENSP00000378442; ENSG00000145335 [P37840-1]
ENST00000420646; ENSP00000396241; ENSG00000145335 [P37840-2]
ENST00000505199; ENSP00000421485; ENSG00000145335 [P37840-3]
ENST00000506244; ENSP00000422238; ENSG00000145335 [P37840-1]
ENST00000508895; ENSP00000426955; ENSG00000145335 [P37840-1]
ENST00000618500; ENSP00000484044; ENSG00000145335 [P37840-3]

Database of genes from NCBI RefSeq genomes

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GeneIDi
6622

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:6622

UCSC genome browser

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UCSCi
uc003hso.3 human [P37840-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08850 mRNA Translation: AAA16117.1
L36674 mRNA Translation: AAA98493.1
L36675 mRNA Translation: AAA98487.1
D31839 mRNA Translation: BAA06625.1
U46901
, U46897, U46898, U46899 Genomic DNA Translation: AAC02114.1
AF163864 Genomic DNA Translation: AAG30302.1
AF163864 Genomic DNA Translation: AAG30303.1
AY049786 mRNA Translation: AAL15443.1
AK290169 mRNA Translation: BAF82858.1
CR457058 mRNA Translation: CAG33339.1
DQ088379 Genomic DNA Translation: AAY88735.1
CH471057 Genomic DNA Translation: EAX06036.1
BC013293 mRNA Translation: AAH13293.1
BC108275 mRNA Translation: AAI08276.1
CCDSiCCDS3634.1 [P37840-1]
CCDS43252.1 [P37840-2]
PIRiA49669
S56746
RefSeqiNP_000336.1, NM_000345.3 [P37840-1]
NP_001139526.1, NM_001146054.1 [P37840-1]
NP_001139527.1, NM_001146055.1 [P37840-1]
NP_009292.1, NM_007308.2 [P37840-2]
XP_011530510.1, XM_011532208.2 [P37840-1]
XP_016864051.1, XM_017008562.1 [P37840-1]
XP_016864052.1, XM_017008563.1 [P37840-1]

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XQ8NMR-A1-140[»]
2JN5NMR-A1-12[»]
2KKWNMR-A1-140[»]
2M55NMR-B1-19[»]
2N0ANMR-A/B/C/D/E/F/G/H/I/J1-140[»]
2X6MX-ray1.62B132-140[»]
3Q25X-ray1.90A1-19[»]
3Q26X-ray1.54A10-42[»]
3Q27X-ray1.30A32-57[»]
3Q28X-ray1.60A58-79[»]
3Q29X-ray2.30A/C1-19[»]
4BXLNMR-C35-56[»]
4R0UX-ray1.38A72-78[»]
4R0WX-ray1.50A70-76[»]
4RIKX-ray1.85A69-77[»]
4RILelectron microscopy1.43A68-78[»]
4ZNNelectron microscopy1.41A47-56[»]
5CRWX-ray1.60B31-41[»]
6A6Belectron microscopy3.07A/B/C/D/E/F/G/H/I/J/K/L37-99[»]
6CU7electron microscopy3.50A/B/C/D/E/F/G/H/I/J1-140[»]
6CU8electron microscopy3.60A/B/C/D/E/F/G/H/I/J1-140[»]
6FLTelectron microscopy3.42A/B/C/D/E/F/G/H/I/J1-121[»]
6H6Belectron microscopy3.40A/B/C/D/E/F/G/H/I/J1-121[»]
DisProtiDP00070
SMRiP37840
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112506, 474 interactors
CORUMiP37840
DIPiDIP-35354N
IntActiP37840, 265 interactors
MINTiP37840
STRINGi9606.ENSP00000338345

Chemistry databases

BindingDBiP37840
ChEMBLiCHEMBL6152

Protein family/group databases

TCDBi1.C.77.1.1 the synuclein (synuclein) family

PTM databases

iPTMnetiP37840
PhosphoSitePlusiP37840
SwissPalmiP37840

Polymorphism and mutation databases

BioMutaiSNCA
DMDMi586067

Proteomic databases

EPDiP37840
jPOSTiP37840
MaxQBiP37840
PaxDbiP37840
PeptideAtlasiP37840
PRIDEiP37840
ProteomicsDBi55279
55280 [P37840-2]
55281 [P37840-3]
TopDownProteomicsiP37840-1 [P37840-1]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
6622
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336904; ENSP00000338345; ENSG00000145335 [P37840-1]
ENST00000345009; ENSP00000343683; ENSG00000145335 [P37840-2]
ENST00000394986; ENSP00000378437; ENSG00000145335 [P37840-1]
ENST00000394989; ENSP00000378440; ENSG00000145335 [P37840-3]
ENST00000394991; ENSP00000378442; ENSG00000145335 [P37840-1]
ENST00000420646; ENSP00000396241; ENSG00000145335 [P37840-2]
ENST00000505199; ENSP00000421485; ENSG00000145335 [P37840-3]
ENST00000506244; ENSP00000422238; ENSG00000145335 [P37840-1]
ENST00000508895; ENSP00000426955; ENSG00000145335 [P37840-1]
ENST00000618500; ENSP00000484044; ENSG00000145335 [P37840-3]
GeneIDi6622
KEGGihsa:6622
UCSCiuc003hso.3 human [P37840-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
6622
DisGeNETi6622

GeneCards: human genes, protein and diseases

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GeneCardsi
SNCA
GeneReviewsiSNCA
HGNCiHGNC:11138 SNCA
HPAiCAB010877
HPA005459
MalaCardsiSNCA
MIMi127750 phenotype
163890 gene
168600 phenotype
168601 phenotype
605543 phenotype
neXtProtiNX_P37840
OpenTargetsiENSG00000145335
Orphaneti411602 Hereditary late-onset Parkinson disease
1648 NON RARE IN EUROPE: Dementia with Lewy body
171695 Parkinsonian-pyramidal syndrome
2828 Young-onset Parkinson disease
PharmGKBiPA35986

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410IWI2 Eukaryota
ENOG4111TDZ LUCA
GeneTreeiENSGT00950000183175
HOGENOMiHOG000008691
InParanoidiP37840
KOiK04528
OMAiSEAYEMP
OrthoDBi716326at2759
PhylomeDBiP37840
TreeFamiTF332776

Enzyme and pathway databases

ReactomeiR-HSA-977225 Amyloid fiber formation
SignaLinkiP37840
SIGNORiP37840

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
SNCA human
EvolutionaryTraceiP37840

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
Alpha-synuclein

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
6622
PMAP-CutDBiP37840

Protein Ontology

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PROi
PR:P37840

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000145335 Expressed in 237 organ(s), highest expression level in bone marrow
ExpressionAtlasiP37840 baseline and differential
GenevisibleiP37840 HS

Family and domain databases

InterProiView protein in InterPro
IPR001058 Synuclein
IPR002460 Synuclein_alpha
PANTHERiPTHR13820 PTHR13820, 1 hit
PTHR13820:SF5 PTHR13820:SF5, 1 hit
PfamiView protein in Pfam
PF01387 Synuclein, 1 hit
PRINTSiPR01212 ASYNUCLEIN
PR01211 SYNUCLEIN

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSYUA_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P37840
Secondary accession number(s): A8K2A4
, Q13701, Q4JHI3, Q6IAU6
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: May 8, 2019
This is version 223 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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