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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000345 6 - 3215 NP_000336 14.46 140 - 1995 7601479 containing exons 2a & 6a (longer than 2b & 6b respectively) encoding for the longest isoform also called NACP140 NM_001146054 4 splicing 3211 NP_001139526 - 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 NM_001146055 5 splicing 3022 NP_001139527 - 140 ubiquination by Parkin in the brain 1995 7601479 lacking exon 3 encoding for a soluble ant glycosylated isoform also called ASP22 NM_007308 4 - 3127 NP_009292 - 112 - 1995 7601479

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine small intestine     highly Endocrine pancreas       moderately Nervous brain       highly   nerve       highly Skin/Tegument skin       moderately Urinary bladder       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Muscular striatum skeletal     Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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