UniProt:P37840 SNCA

chain
  • chain:1-140
checksum 6BB2F12128931663
comment
  • FUNCTION 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 Ca(2+) 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).SUBUNIT 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). Interacts with SERF1A; this interaction promotes the aggregation of SNCA (PubMed:22854022, PubMed:31034892).TISSUE SPECIFICITY Highly expressed in presynaptic terminals in the central nervous system. Expressed principally in brain.DOMAIN 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.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.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 (By similarity).PTM Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.DISEASE 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.SIMILARITY Belongs to the synuclein family.
crossReference
databaseName UniProt
dbId 65462
description
  • recommendedName: Alpha-synuclein alternativeName: Non-A beta component of AD amyloid alternativeName: Non-A4 component of amyloid precursor shortName:NACP
displayName UniProt:P37840 SNCA
geneName
  • SNCA
  • NACP
  • PARK1
identifier P37840
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Alternative splicing
  • Alzheimer disease
  • Amyloid
  • Cell junction
  • Copper
  • Cytoplasm
  • Direct protein sequencing
  • Disease variant
  • Membrane
  • Metal-binding
  • Neurodegeneration
  • Nucleus
  • Parkinson disease
  • Parkinsonism
  • Phosphoprotein
  • Reference proteome
  • Repeat
  • Secreted
  • Synapse
  • Ubl conjugation
modified [InstanceEdit:11703684] Shorser, Solomon, 2021-05-28
name
  • SNCA
otherIdentifier
  • 0004070292
  • 0004730609
  • 11731446_s_at
  • 11731447_x_at
  • 11731448_a_at
  • 11739782_a_at
  • 11753730_a_at
  • 11753731_x_at
  • 11754090_a_at
  • 16977986
  • 204466_s_at
  • 204467_s_at
  • 207827_x_at
  • 211546_x_at
  • 236081_at
  • 2777711
  • 2777712
  • 2777715
  • 2777716
  • 2777717
  • 2777718
  • 2777719
  • 2777722
  • 2777744
  • 2777746
  • 2777749
  • 2777750
  • 2777751
  • 2777752
  • 2777753
  • 2777754
  • 2777756
  • 3468050
  • 37291_r_at
  • 44191_at
  • 6622
  • 8101762
  • A_23_P29939
  • A_32_P109653
  • GE57593
  • GO:0000122
  • GO:0000149
  • GO:0000287
  • GO:0000976
  • GO:0001774
  • GO:0001921
  • GO:0001933
  • GO:0001956
  • GO:0001963
  • GO:0002376
  • GO:0003674
  • GO:0003677
  • GO:0003779
  • GO:0004860
  • GO:0005507
  • GO:0005509
  • GO:0005515
  • GO:0005543
  • GO:0005575
  • GO:0005576
  • GO:0005615
  • GO:0005622
  • GO:0005634
  • GO:0005635
  • GO:0005640
  • GO:0005737
  • GO:0005739
  • GO:0005741
  • GO:0005743
  • GO:0005758
  • GO:0005759
  • GO:0005764
  • GO:0005773
  • GO:0005783
  • GO:0005791
  • GO:0005794
  • GO:0005829
  • GO:0005840
  • GO:0005856
  • GO:0005886
  • GO:0005938
  • GO:0005975
  • GO:0006091
  • GO:0006464
  • GO:0006469
  • GO:0006629
  • GO:0006631
  • GO:0006638
  • GO:0006644
  • GO:0006790
  • GO:0006810
  • GO:0006914
  • GO:0006915
  • GO:0006919
  • GO:0006950
  • GO:0007005
  • GO:0007006
  • GO:0007010
  • GO:0007165
  • GO:0007267
  • GO:0007268
  • GO:0007568
  • GO:0008017
  • GO:0008021
  • GO:0008092
  • GO:0008150
  • GO:0008198
  • GO:0008219
  • GO:0008270
  • GO:0008289
  • GO:0008344
  • GO:0009056
  • GO:0009058
  • GO:0010040
  • GO:0010517
  • GO:0010642
  • GO:0014048
  • GO:0014059
  • GO:0015629
  • GO:0016020
  • GO:0016079
  • GO:0016082
  • GO:0016192
  • GO:0016234
  • GO:0016491
  • GO:0019894
  • GO:0019899
  • GO:0019904
  • GO:0022607
  • GO:0022898
  • GO:0030054
  • GO:0030234
  • GO:0030424
  • GO:0030426
  • GO:0030544
  • GO:0030659
  • GO:0030672
  • GO:0031092
  • GO:0031115
  • GO:0031410
  • GO:0031623
  • GO:0031648
  • GO:0032026
  • GO:0032410
  • GO:0032496
  • GO:0032769
  • GO:0032991
  • GO:0033138
  • GO:0034330
  • GO:0034341
  • GO:0034599
  • GO:0034641
  • GO:0035067
  • GO:0035493
  • GO:0035543
  • GO:0040011
  • GO:0040012
  • GO:0042220
  • GO:0042393
  • GO:0042416
  • GO:0042417
  • GO:0042493
  • GO:0042592
  • GO:0042775
  • GO:0042802
  • GO:0043014
  • GO:0043025
  • GO:0043027
  • GO:0043030
  • GO:0043065
  • GO:0043066
  • GO:0043154
  • GO:0043167
  • GO:0043195
  • GO:0043226
  • GO:0043231
  • GO:0043274
  • GO:0043524
  • GO:0043679
  • GO:0044281
  • GO:0044344
  • GO:0045202
  • GO:0045807
  • GO:0045920
  • GO:0045921
  • GO:0045963
  • GO:0046872
  • GO:0046928
  • GO:0047485
  • GO:0048148
  • GO:0048156
  • GO:0048168
  • GO:0048169
  • GO:0048471
  • GO:0048487
  • GO:0048488
  • GO:0048489
  • GO:0048856
  • GO:0050729
  • GO:0050806
  • GO:0050808
  • GO:0050812
  • GO:0050877
  • GO:0051219
  • GO:0051259
  • GO:0051262
  • GO:0051276
  • GO:0051281
  • GO:0051583
  • GO:0051585
  • GO:0051612
  • GO:0051621
  • GO:0051622
  • GO:0055085
  • GO:0060079
  • GO:0060291
  • GO:0060732
  • GO:0061024
  • GO:0065003
  • GO:0070495
  • GO:0070555
  • GO:0070840
  • GO:0071280
  • GO:0071872
  • GO:0071902
  • GO:0097435
  • GO:0098793
  • GO:0099512
  • GO:1901214
  • GO:1901215
  • GO:1901216
  • GO:1902957
  • GO:1903136
  • GO:1903284
  • GO:1903285
  • GO:1903421
  • GO:1903426
  • GO:1904307
  • GO:1904715
  • GO:1905606
  • GO:1990000
  • GO:2000377
  • HMNXSV003001866
  • HMNXSV003022460
  • Hs.21374.0.A1_3p_at
  • Hs.76930.1.A1_3p_a_at
  • ILMN_1701933
  • ILMN_1766165
  • PH_hs_0004441
  • TC04001383.hg
  • U46901_at
  • g556211_3p_x_at
  • g556213_3p_a_at
  • g6806896_3p_a_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • SYUA_HUMAN
  • A8K2A4
  • Q13701
  • Q4JHI3
  • Q6IAU6
sequenceLength 140
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/P37840

Referrals

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