SYUA_PANPA
ID SYUA_PANPA Reviewed; 140 AA.
AC P61144;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Alpha-synuclein;
GN Name=SNCA;
OS Pan paniscus (Pygmy chimpanzee) (Bonobo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9597;
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: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; AY362299; AAQ85068.1; -; Genomic_DNA.
DR EMBL; AY362295; AAQ85068.1; JOINED; Genomic_DNA.
DR EMBL; AY362296; AAQ85068.1; JOINED; Genomic_DNA.
DR EMBL; AY362297; AAQ85068.1; JOINED; Genomic_DNA.
DR EMBL; AY362298; AAQ85068.1; JOINED; Genomic_DNA.
DR RefSeq; XP_003829936.1; XM_003829888.2.
DR RefSeq; XP_003829937.1; XM_003829889.2.
DR RefSeq; XP_003829938.1; XM_003829890.2.
DR RefSeq; XP_008953542.1; XM_008955294.1.
DR AlphaFoldDB; P61144; -.
DR SMR; P61144; -.
DR STRING; 9597.XP_003829936.1; -.
DR Ensembl; ENSPPAT00000027770; ENSPPAP00000006465; ENSPPAG00000025110.
DR GeneID; 100984304; -.
DR KEGG; pps:100984304; -.
DR CTD; 6622; -.
DR eggNOG; ENOG502S0Q7; Eukaryota.
DR GeneTree; ENSGT00950000183175; -.
DR OMA; VHGVTTX; -.
DR OrthoDB; 1544450at2759; -.
DR Proteomes; UP000240080; Chromosome 4.
DR Bgee; ENSPPAG00000025110; Expressed in prefrontal cortex and 6 other tissues.
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; IEA:Ensembl.
DR GO; GO:0005938; C:cell cortex; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
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: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: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; IEA:Ensembl.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IEA:Ensembl.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IEA:Ensembl.
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 3: Inferred from homology;
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_0000184027"
FT REGION 100..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; 14460 MW; 6BB2F12128931663 CRC64;
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK
EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL GKNEEGAPQE GILEDMPVDP
DNEAYEMPSE EGYQDYEPEA
