SNCA
entrez
6622
canonical
uniprot
P37840
canonical
ensembl
ENSG00000145335
resolver
ensp
ENSP00000338345
resolver
ensp
ENSP00000378437
resolver
ensp
ENSP00000378442
resolver
ensp
ENSP00000396241
resolver
ensp
ENSP00000422238
resolver
ensp
ENSP00000426955
resolver
ensp
ENSP00000635249
resolver
ensp
ENSP00000768672
resolver
genesymbol
SNCA
resolver
genesymbol_syn
NACP
resolver
genesymbol_syn
PARK1
resolver
hgnc
HGNC:11138
resolver
uniprot
A8K2A4
resolver
uniprot
H6UYS5
resolver
uniprot
Q13701
resolver
uniprot
Q4JHI3
resolver
uniprot
Q6IAU6
resolver
uniprot_entry
H6UYS5_HUMAN
resolver
uniprot_entry
SYUA_HUMAN
resolver
uniprot_sec
A8K2A4
resolver
uniprot_sec
Q13701
resolver
uniprot_sec
Q4JHI3
resolver
uniprot_sec
Q6IAU6
resolver
amino_acid_sequence
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA
uniprot
proteins
disease_involvement
DISEASE: Note=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.; DISEASE: Parkinson disease 1, autosomal dominant (PARK1) [MIM:168601]: A 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. {ECO:0000269|PubMed:14755719, ECO:0000269|PubMed:23427326, ECO:0000269|PubMed:23457019, ECO:0000269|PubMed:24936070, ECO:0000269|PubMed:25561023, ECO:0000269|PubMed:9197268, ECO:0000269|PubMed:9462735}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Parkinson disease 4, autosomal dominant (PARK4) [MIM:605543]: A 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. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Dementia, Lewy body (DLB) [MIM:127750]: A 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. {ECO:0000269|PubMed:14755719}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:28288128, PubMed:30404828). 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 Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Also acts 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). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590). {ECO:0000269|PubMed:20798282, ECO:0000269|PubMed:26442590, ECO:0000269|PubMed:28288128, ECO:0000269|PubMed:30404828}.
uniprot
proteins
mass_dalton
14460
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="D->A: Impairs copper-binding."; /evidence="ECO:0000269|PubMed:21319811"; MUTAGEN 35; /note="E->K: No effect on oligomerization."; /evidence="ECO:0000269|PubMed:25561023"; MUTAGEN 39; /note="Y->F: No effect on osmotic stress-induced phosphorylation."; /evidence="ECO:0000269|PubMed:12893833"; MUTAGEN 50; /note="H->A: Impairs copper-binding."; /evidence="ECO:0000269|PubMed:21319811"; MUTAGEN 57; /note="E->K: Increases oligomerization."; /evidence="ECO:0000269|PubMed:25561023"; MUTAGEN 67..71; /note="Missing: Reduces polymerization into amyloid fibrils."; /evidence="ECO:0000269|PubMed:19722699"; MUTAGEN 71..82; /note="Missing: Impairs polymerization into amyloid fibrils."; /evidence="ECO:0000269|PubMed:19722699"; MUTAGEN 76..77; /note="Missing: Impairs polymerization into amyloid fibrils."; /evidence="ECO:0000269|PubMed:19722699"; MUTAGEN 76; /note="Missing: Does not affect polymerization into amyloid fibrils."; MUTAGEN 77; /note="Missing: Does not affect polymerization into amyloid fibrils."; /evidence="ECO:0000269|PubMed:19722699"; MUTAGEN 78; /note="Missing: Does not affect polymerization into amyloid fibrils."; /evidence="ECO:0000269|PubMed:19722699"; MUTAGEN 85..94; /note="Missing: Reduces polymerization into amyloid fibrils."; /evidence="ECO:0000269|PubMed:19722699"; MUTAGEN 125; /note="Y->F: Abolishes osmotic stress-induced phosphorylation."; /evidence="ECO:0000269|PubMed:12893833"; MUTAGEN 133; /note="Y->F: No effect on osmotic stress-induced phosphorylation."; /evidence="ECO:0000269|PubMed:12893833"; MUTAGEN 136; /note="Y->F: No effect on osmotic stress-induced phosphorylation."; /evidence="ECO:0000269|PubMed:12893833
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:10617630, ECO:0000269|PubMed:10852916, ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11813001, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:24936070}.; PTM: 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.; PTM: Ubiquitinated. The predominant conjugate is the diubiquitinated form. {ECO:0000250|UniProtKB:P37377}.; PTM: Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure. {ECO:0000269|PubMed:22407793}.
uniprot
proteins
protein_family
Synuclein family
uniprot
proteins
pubmed
10617630
uniprot
proteins
pubmed
10852916
uniprot
proteins
pubmed
11156617
uniprot
proteins
pubmed
11162638
uniprot
proteins
pubmed
11813001
uniprot
proteins
pubmed
11821392
uniprot
proteins
pubmed
12558071
uniprot
proteins
pubmed
12859192
uniprot
proteins
pubmed
12859200
uniprot
proteins
pubmed
12893833
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14755719
uniprot
proteins
pubmed
15207266
uniprot
proteins
pubmed
15282274
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498564
uniprot
proteins
pubmed
15615727
uniprot
proteins
pubmed
19722699
uniprot
proteins
pubmed
19762560
uniprot
proteins
pubmed
20798282
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21319811
uniprot
proteins
pubmed
21462277
uniprot
proteins
pubmed
21841800
uniprot
proteins
pubmed
22407793
uniprot
proteins
pubmed
22854022
uniprot
proteins
pubmed
23427326
uniprot
proteins
pubmed
23457019
uniprot
proteins
pubmed
23607618
uniprot
proteins
pubmed
24936070
uniprot
proteins
pubmed
25561023
uniprot
proteins
pubmed
26352473
uniprot
proteins
pubmed
26442590
uniprot
proteins
pubmed
27018801
uniprot
proteins
pubmed
27597756
uniprot
proteins
pubmed
28288128
uniprot
proteins
pubmed
30190461
uniprot
proteins
pubmed
30404828
uniprot
proteins
pubmed
31034892
uniprot
proteins
pubmed
33657088
uniprot
proteins
pubmed
7601450
uniprot
proteins
pubmed
7802671
uniprot
proteins
pubmed
8194594
uniprot
proteins
pubmed
8248242
uniprot
proteins
pubmed
9197268
uniprot
proteins
pubmed
9462735
uniprot
proteins
sequence_length
140
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19762560, ECO:0000269|PubMed:24936070, ECO:0000269|PubMed:25561023, ECO:0000269|PubMed:26442590, ECO:0000269|PubMed:31034892, ECO:0000269|PubMed:33657088}. Membrane {ECO:0000269|PubMed:24936070}. Nucleus {ECO:0000269|PubMed:12859192, ECO:0000269|PubMed:24936070}. Synapse {ECO:0000269|PubMed:15282274}. Secreted {ECO:0000269|PubMed:24936070}. Cell projection, axon {ECO:0000250|UniProtKB:O55042}. Note=Membrane-bound in dopaminergic neurons (PubMed:15282274). Expressed and colocalized with SEPTIN4 in dopaminergic axon terminals, especially at the varicosities (By similarity). {ECO:0000250|UniProtKB:O55042, ECO:0000269|PubMed:15282274}.
uniprot
proteins