ID   SYUA_BOVIN              Reviewed;         140 AA.
AC   Q3T0G8;
DT   10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 1.
DT   03-AUG-2022, entry version 120.
DE   RecName: Full=Alpha-synuclein;
GN   Name=SNCA;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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:P37377, ECO:0000250|UniProtKB:P37840}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P37840}.
CC       Membrane {ECO:0000250|UniProtKB:P37840}. Nucleus
CC       {ECO:0000250|UniProtKB:P37840}. Synapse {ECO:0000250|UniProtKB:P37840}.
CC       Secreted {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; BC102402; AAI02403.1; -; mRNA.
DR   RefSeq; NP_001029213.1; NM_001034041.2.
DR   RefSeq; XP_005207811.1; XM_005207754.3.
DR   RefSeq; XP_005207812.1; XM_005207755.3.
DR   RefSeq; XP_005207813.1; XM_005207756.3.
DR   RefSeq; XP_005207814.1; XM_005207757.3.
DR   RefSeq; XP_005207815.1; XM_005207758.3.
DR   AlphaFoldDB; Q3T0G8; -.
DR   BioGRID; 159869; 1.
DR   STRING; 9913.ENSBTAP00000021300; -.
DR   PaxDb; Q3T0G8; -.
DR   PRIDE; Q3T0G8; -.
DR   Ensembl; ENSBTAT00000021300; ENSBTAP00000021300; ENSBTAG00000024957.
DR   Ensembl; ENSBTAT00000066780; ENSBTAP00000061053; ENSBTAG00000024957.
DR   GeneID; 282857; -.
DR   KEGG; bta:282857; -.
DR   CTD; 6622; -.
DR   VEuPathDB; HostDB:ENSBTAG00000024957; -.
DR   VGNC; VGNC:35059; SNCA.
DR   eggNOG; ENOG502S0Q7; Eukaryota.
DR   GeneTree; ENSGT00950000183175; -.
DR   HOGENOM; CLU_129378_1_0_1; -.
DR   InParanoid; Q3T0G8; -.
DR   OMA; VHGVTTX; -.
DR   OrthoDB; 1544450at2759; -.
DR   TreeFam; TF332776; -.
DR   Proteomes; UP000009136; Chromosome 6.
DR   Bgee; ENSBTAG00000024957; Expressed in Ammon's horn and 99 other tissues.
DR   ExpressionAtlas; Q3T0G8; baseline.
DR   GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:0043679; C:axon terminus; IBA:GO_Central.
DR   GO; GO:0005938; C:cell cortex; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR   GO; GO:0016234; C:inclusion body; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR   GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR   GO; GO:0031092; C:platelet alpha granule membrane; IEA:Ensembl.
DR   GO; GO:0098794; C:postsynapse; IEA:GOC.
DR   GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR   GO; GO:0099512; C:supramolecular fiber; IEA:Ensembl.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IEA:Ensembl.
DR   GO; GO:0003779; F:actin binding; IEA:Ensembl.
DR   GO; GO:0043014; F:alpha-tubulin binding; IEA:Ensembl.
DR   GO; GO:0050544; F:arachidonic acid binding; IEA:Ensembl.
DR   GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR   GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR   GO; GO:1903136; F:cuprous ion binding; IBA:GO_Central.
DR   GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IEA:Ensembl.
DR   GO; GO:0070840; F:dynein complex binding; IEA:Ensembl.
DR   GO; GO:0008198; F:ferrous iron binding; IEA:Ensembl.
DR   GO; GO:0042393; F:histone binding; IEA:Ensembl.
DR   GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0019894; F:kinesin binding; IEA:Ensembl.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:Ensembl.
DR   GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
DR   GO; GO:0051219; F:phosphoprotein binding; IEA:Ensembl.
DR   GO; GO:0000149; F:SNARE binding; IEA:Ensembl.
DR   GO; GO:0048156; F:tau protein binding; IEA:Ensembl.
DR   GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR   GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR   GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR   GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0042416; P:dopamine biosynthetic process; IEA:Ensembl.
DR   GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl.
DR   GO; GO:0006631; P:fatty acid metabolic process; IEA:Ensembl.
DR   GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR   GO; GO:0001774; P:microglial cell activation; IEA:Ensembl.
DR   GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IEA:Ensembl.
DR   GO; GO:0007006; P:mitochondrial membrane organization; IEA:Ensembl.
DR   GO; GO:1904715; P:negative regulation of chaperone-mediated autophagy; IEA:Ensembl.
DR   GO; GO:0051585; P:negative regulation of dopamine uptake involved in synaptic transmission; IEA:Ensembl.
DR   GO; GO:0045920; P:negative regulation of exocytosis; IEA:Ensembl.
DR   GO; GO:0035067; P:negative regulation of histone acetylation; IEA:Ensembl.
DR   GO; GO:0031115; P:negative regulation of microtubule polymerization; IEA:Ensembl.
DR   GO; GO:0032769; P:negative regulation of monooxygenase activity; IEA:Ensembl.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0051622; P:negative regulation of norepinephrine uptake; IEA:Ensembl.
DR   GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0051612; P:negative regulation of serotonin uptake; IEA:Ensembl.
DR   GO; GO:0070495; P:negative regulation of thrombin-activated receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0032410; P:negative regulation of transporter activity; IEA:Ensembl.
DR   GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0006638; P:neutral lipid metabolic process; IEA:Ensembl.
DR   GO; GO:0006644; P:phospholipid metabolic process; IEA:Ensembl.
DR   GO; GO:0045807; P:positive regulation of endocytosis; IEA:Ensembl.
DR   GO; GO:0045921; P:positive regulation of exocytosis; IEA:Ensembl.
DR   GO; GO:1903284; P:positive regulation of glutathione peroxidase activity; IEA:Ensembl.
DR   GO; GO:1903285; P:positive regulation of hydrogen peroxide catabolic process; IEA:Ensembl.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR   GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; IEA:Ensembl.
DR   GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR   GO; GO:0001956; P:positive regulation of neurotransmitter secretion; IEA:Ensembl.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR   GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IEA:Ensembl.
DR   GO; GO:0001921; P:positive regulation of receptor recycling; IEA:Ensembl.
DR   GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR   GO; GO:0035543; P:positive regulation of SNARE complex assembly; IEA:Ensembl.
DR   GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR   GO; GO:0051262; P:protein tetramerization; IEA:Ensembl.
DR   GO; GO:0031623; P:receptor internalization; IEA:Ensembl.
DR   GO; GO:0050812; P:regulation of acyl-CoA biosynthetic process; IEA:Ensembl.
DR   GO; GO:0014059; P:regulation of dopamine secretion; IEA:Ensembl.
DR   GO; GO:0014048; P:regulation of glutamate secretion; IEA:Ensembl.
DR   GO; GO:0040012; P:regulation of locomotion; IEA:Ensembl.
DR   GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR   GO; GO:0043030; P:regulation of macrophage activation; IEA:Ensembl.
DR   GO; GO:1901214; P:regulation of neuron death; IBA:GO_Central.
DR   GO; GO:0010517; P:regulation of phospholipase activity; IEA:Ensembl.
DR   GO; GO:1905606; P:regulation of presynapse assembly; IEA:Ensembl.
DR   GO; GO:0022898; P:regulation of transmembrane transporter activity; IEA:Ensembl.
DR   GO; GO:0034341; P:response to interferon-gamma; IEA:Ensembl.
DR   GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR   GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0035493; P:SNARE complex assembly; IEA:Ensembl.
DR   GO; GO:0050808; P:synapse organization; IBA:GO_Central.
DR   GO; GO:0001963; P:synaptic transmission, dopaminergic; IEA:Ensembl.
DR   GO; GO:0048488; P:synaptic vesicle endocytosis; IBA:GO_Central.
DR   GO; GO:0016082; P:synaptic vesicle priming; IEA:Ensembl.
DR   GO; GO:0048489; P:synaptic vesicle transport; IEA:Ensembl.
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   2: Evidence at transcript level;
KW   Acetylation; Cell projection; Copper; Cytoplasm; Membrane; Metal-binding;
KW   Nucleus; Phosphoprotein; Reference proteome; Repeat; Secreted; Synapse;
KW   Ubl conjugation.
FT   CHAIN           1..140
FT                   /note="Alpha-synuclein"
FT                   /id="PRO_0000184019"
FT   REGION          93..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         87
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P37840"
FT   MOD_RES         125
FT                   /note="Phosphotyrosine; by FYN"
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;  14508 MW;  1F37F1A7B795536C CRC64;
     MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GRTKEGVLYV GSKTKEGVVH GVTTVAEKTK
     EQVTNVGEAV VTGVTAVAQK TVEGAGSIAA ATGFGKKDHM GKGEEGASQE GILEDMPVDP
     DNEAYEMPSE EGYQDYEPEA