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FLASH GENE
Symbol SNCA contributors: mct - updated : 05-07-2010
HGNC name synuclein, alpha (non A4 component of amyloid precursor)
HGNC id 11138
Corresponding disease
PARK1 Parkinson disease, 1
Location 4q22.1      Physical location : 90.645.250 - 90.759.447
Synonym name
  • non A-beta component of AD amyloid
  • alpha-synuclein
  • Synonym symbol(s) NACP, PD1, PARK1, PARK4, NACP112, NACP140, aSYN
    DNA
    TYPE functioning gene
    STRUCTURE 111.43 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    motif repetitive sequence
    text structure three sp1 binding sites, polymorphic NACP-Rep1 elements modulating the activity of SNCA promoter/enhancer
    MAPPING cloned Y linked N status confirmed
    Physical map
    DHRS8 4q22.1 dehydrogenase/reductase (SDR family) member 8 NUDT9 4q21.3 nudix (nucleoside diphosphate linked moiety X)-type motif 9 SPARCL1 4q27 SPARC-like 1 (mast9, hevin) DSPP 4q21.3 dentin sialophosphoprotein DMP1 4q21.2-q21.3 dentin matrix acidic phosphoprotein LOC391677 4 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein IBSP 4q21-q25 integrin-binding sialoprotein (bone sialoprotein, bone sialoprotein II) MEPE 4q21.1 matrix, extracellular phosphoglycoprotein with ASARM motif (bone) HSPCP1 4q21-q25 heat shock 90kDa protein 1, beta pseudogene 1 SPP1 4q21-q25 secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) PKD2 4q22 polycystic kidney disease 2 (autosomal dominant) ABCG2 4q22 ATP-binding cassette, sub-family G (WHITE), member 2 DKFZp761G058 4q22.1 hypothetical protein DKFZp761G058 CEB1 4q22.1-q23 hypothetical protein DKFZp761G058 MGC14156 4q22.1 hypothetical protein MGC14156 HERC3 4q21 hect domain and RLD 3 DRLM FAM13A1 4q21 family with sequence similarity 13, member A1 LOC389211 4 similar to expressed sequence AW060714 TIGD2 4q21.3 tigger transposable element derived 2 LOC285513 4q22.1 hypothetical protein LOC285513 SNCA 4q21-q22 synuclein, alpha (non A4 component of amyloid precursor) MMRN 4q22 multimerin KIAA1680 4q22 multimerin TMSL3 4q22.1 thymosin-like 3 LOC389212 4 LOC389212
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 3215 14.46 140 - 1995 7601479
  • containing exons 2a & 6a (longer than 2b & 6b respectively)
  • encoding for the longest isoform
  • also called NACP140
  • 4 splicing 3211 - 140 fetal and adult brain (highly) and skeletal muscle, pancreas, not in liver 1995 7601479
  • containing exons 2b et 6b (shorter than 2a et 6a respectively)
  • lacking exons 1 & 5
  • also called NACP112
  • 5 splicing 3022 - 140 ubiquination by Parkin in the brain 1995 7601479
  • lacking exon 3
  • encoding for a soluble ant glycosylated isoform
  • also called ASP22
  • 4 - 3127 - 112 - 1995 7601479
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
    Endocrinepancreas   moderately
    Nervousbrain   highly
     nerve   highly
    Skin/Tegumentskin   moderately
    Urinarybladder   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines highly in ovarian and breast carcinomas
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven imperfect repeats of 11 aminoacids with the consensus core KTKEGV, homolog to 14-3-3 proteins YWHAs
  • a twelve amino-acids stretch in the hydrophobic domain essential for filament assembly
  • C-terminal peptide with a second acidic repat important for the chaperone activity
  • conjugated ubiquitinated
    HOMOLOGY
    interspecies homolog to rattus Snca (95.00 pc)
    homolog to murine Snca (95.00 pc)
    Homologene
    FAMILY
  • synuclein family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • concentrated in presynaptic nerve terminals
  • mitochondrial translocation is promoted by intracellular acidification
  • basic FUNCTION
  • involved in exocytosis of synaptic vesicles, in synapse maintenance and plasticity
  • induction of mitochondrial dysfunction and oxidative stress
  • contributing to cell death in neurodegenerative diseases and accumulating in dentritic neurites and in Lewy bodies (neuronal and oligoendrocytic aggregates)
  • regulating vesicles recycling via its inhibition of PLD2 and/or its ability to bind fatty acids
  • playing a vital role in the modulation of dopamine transporter (DAT) function
  • negative regulator of synaptic vesicle priming before fusion, that causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive
  • direct role in mitochondrial physiology, especially under pathological conditions, and in principle, link SNCA to other Parkinson disease genes in regulating mitochondrial homeostasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • non A/beta constituent of Alzheimer amyloid precursor alpha
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • synphilin 1 (SNCAIP) binding
  • associating with PRKC and other proteins
  • binding to 14-3-3 (YWAHs) and acting as a potential chaperone with UBCH7 (isoform ASP22)
  • disrupts cellular Rab homeostasis
  • the specific interaction between SNCA and SNCAIP provides mechanistic insights into the inclusion-body formation in cells and pathological implication in Parkinson disease
  • binds TRAF6 that enhances its ubiquitination with atypical chains (possibility that SNCA might be an additional Parkinson disease-associated target of TRAF6 ligase activity)
  • cell & other
    REGULATION
    Other regulated by PARP1(binding to NACP-Rep1)
    phosphorylated by PLK2 in neurons (Inglis, 2009)
    its monoubiquitylation by SIAH is decreased by SNCAIP
    NEDD4 overexpression enhances SNCA ubiquitination and clearance by a lysosomal process requiring components of the endosomal-sorting complex required for transport
    ASSOCIATED DISORDERS
    corresponding disease(s) PARK1
    related resource Alpha - Synuclein Locus Mutation Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   amplification    
    triplicated locus in Parkinson 4 (PARK4)
    Susceptibility to sporadic Parkinson disease (PD)
    Variant & Polymorphism SNP
  • "protective" genotype 259/259 of the PD-associated promoter repeat NACP-Rep1 is associated with lower protein levels in blood
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS