SYUA_SAGLB
ID SYUA_SAGLB Reviewed; 140 AA.
AC P61147;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Alpha-synuclein;
GN Name=SNCA;
OS Saguinus labiatus (Red-chested mustached tamarin).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Saguinus.
OX NCBI_TaxID=78454;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15028296; DOI=10.1016/j.ygeno.2003.09.016;
RA Hamilton B.A.;
RT "Alpha-synuclein A53T substitution associated with Parkinson disease also
RT marks the divergence of Old World and New World primates.";
RL Genomics 83:739-742(2004).
CC -!- FUNCTION: Neuronal protein that plays several roles in synaptic
CC activity such as regulation of synaptic vesicle trafficking and
CC subsequent neurotransmitter release (By similarity). Participates as a
CC monomer in synaptic vesicle exocytosis by enhancing vesicle priming,
CC fusion and dilation of exocytotic fusion pores (By similarity).
CC Mechanistically, acts by increasing local Ca(2+) release from
CC microdomains which is essential for the enhancement of ATP-induced
CC exocytosis (By similarity). Acts also as a molecular chaperone in its
CC multimeric membrane-bound state, assisting in the folding of synaptic
CC fusion components called SNAREs (Soluble NSF Attachment Protein
CC REceptors) at presynaptic plasma membrane in conjunction with cysteine
CC string protein-alpha/DNAJC5 (By similarity). This chaperone activity is
CC important to sustain normal SNARE-complex assembly during aging (By
CC similarity). Also plays a role in the regulation of the dopamine
CC neurotransmission by associating with the dopamine transporter (DAT1)
CC and thereby modulating its activity (By similarity).
CC {ECO:0000250|UniProtKB:P37840}.
CC -!- SUBUNIT: Soluble monomer. Homotetramer. A dynamic intracellular
CC population of tetramers and monomers coexists normally and the tetramer
CC plays an essential role in maintaining homeostasis (By similarity).
CC Interacts with UCHL1 (By similarity). Interacts with phospholipase D
CC and histones. Interacts (via N-terminus) with synphilin-1/SNCAIP; this
CC interaction promotes formation of SNCA inclusions in the cytoplasm.
CC Interacts with CALM1. Interacts with STXBP1; this interaction controls
CC SNCA self-replicating aggregation. Interacts with SNARE components
CC VAMP2 and SNAP25; these interactions allows SNARE complex assembly and
CC integrity (By similarity). Interacts with RPH3A and RAB3A (By
CC similarity). Interacts with SERF1A; this interaction promotes the
CC aggregation of SNCA (By similarity). Interacts with SEPTIN4 (By
CC similarity). {ECO:0000250|UniProtKB:O55042,
CC ECO:0000250|UniProtKB:P37840}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P37840}. Membrane
CC {ECO:0000250|UniProtKB:P37840}. Nucleus {ECO:0000250|UniProtKB:P37840}.
CC Synapse {ECO:0000250|UniProtKB:P37840}. Secreted
CC {ECO:0000250|UniProtKB:P37840}. Cell projection, axon
CC {ECO:0000250|UniProtKB:O55042}. Note=Membrane-bound in dopaminergic
CC neurons (By similarity). Expressed and colocalized with SEPTIN4 in
CC dopaminergic axon terminals, especially at the varicosities (By
CC similarity). {ECO:0000250|UniProtKB:O55042,
CC ECO:0000250|UniProtKB:P37840}.
CC -!- PTM: Phosphorylated, predominantly on serine residues. Phosphorylated
CC on Tyr-125 upon osmotic stress. {ECO:0000250|UniProtKB:P37840}.
CC -!- PTM: Ubiquitinated. The predominant conjugate is the diubiquitinated
CC form. {ECO:0000250|UniProtKB:P37377}.
CC -!- PTM: Acetylation at Met-1 seems to be important for proper folding and
CC native oligomeric structure. {ECO:0000250|UniProtKB:P37840}.
CC -!- SIMILARITY: Belongs to the synuclein family. {ECO:0000305}.
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DR EMBL; AY362329; AAQ85075.1; -; Genomic_DNA.
DR EMBL; AY362325; AAQ85075.1; JOINED; Genomic_DNA.
DR EMBL; AY362326; AAQ85075.1; JOINED; Genomic_DNA.
DR EMBL; AY362327; AAQ85075.1; JOINED; Genomic_DNA.
DR EMBL; AY362328; AAQ85075.1; JOINED; Genomic_DNA.
DR AlphaFoldDB; P61147; -.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0014059; P:regulation of dopamine secretion; IEA:InterPro.
DR InterPro; IPR001058; Synuclein.
DR InterPro; IPR002460; Synuclein_alpha.
DR PANTHER; PTHR13820; PTHR13820; 1.
DR PANTHER; PTHR13820:SF5; PTHR13820:SF5; 1.
DR Pfam; PF01387; Synuclein; 1.
DR PRINTS; PR01212; ASYNUCLEIN.
DR PRINTS; PR01211; SYNUCLEIN.
PE 3: Inferred from homology;
KW Acetylation; Cell projection; Copper; Cytoplasm; Membrane; Metal-binding;
KW Nucleus; Phosphoprotein; Repeat; Secreted; Synapse; Ubl conjugation.
FT CHAIN 1..140
FT /note="Alpha-synuclein"
FT /id="PRO_0000184032"
FT REGION 99..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 111..140
FT /note="Interaction with SERF1A"
FT /evidence="ECO:0000250|UniProtKB:P37840"
FT COMPBIAS 116..140
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 2
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250"
FT BINDING 50
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P37840"
FT MOD_RES 125
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P37840"
FT MOD_RES 129
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:P37840"
SQ SEQUENCE 140 AA; 14527 MW; AAA56F58CF1D4240 CRC64;
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVTTVAEKTK
EQVTNVGGAV VTGVTAVAQK TVEGAGNIAA ATGFVRKDHL GKSEEGAPQE GILEDMPVDP
DNEAYEMPSE EGYQDYEPEA
