[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 61-95.
TISSUE=Brain;
PubMed=8248242 [NCBI, ExPASy, EBI, Israel, Japan]
Ueda K.,
Fukushima H.,
Masliah E.,
Xia Y.,
Iwai A.,
Yoshimoto M.,
Otero D.A.,
Kondo J.,
Ihara Y.,
Saitoh T.;
"Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease.";
Proc. Natl. Acad. Sci. U.S.A. 90:11282-11286(1993).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2-4 AND 2-5).
DOI=10.1016/0888-7543(95)80208-4; PubMed=7601450 [NCBI, ExPASy, EBI, Israel, Japan]
Campion D.,
Martin C.,
Heilig R.,
Charbonnier F.,
Moreau V.,
Flaman J.-M.,
Petit J.-L.,
Hannequin D.,
Brice A.,
Frebourg T.;
"The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease.";
Genomics 26:254-257(1995).
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[3]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2-4).
TISSUE=Brain;
DOI=10.1006/bbrc.1994.2816; PubMed=7802671 [NCBI, ExPASy, EBI, Israel, Japan]
Ueda K.,
Saitoh T.,
Mori H.;
"Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A beta component of Alzheimer's disease amyloid.";
Biochem. Biophys. Res. Commun. 205:1366-1372(1994).
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[4]
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NUCLEOTIDE SEQUENCE.
Xia Y.,
Silva R.D.,
Chen X.H.,
Saitoh T.;
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
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[5]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2-4).
DOI=10.1101/gr.165801; PubMed=11156617 [NCBI, ExPASy, EBI, Israel, Japan]
Touchman J.W.,
Dehejia A.,
Chiba-Falek O.,
Cabin D.E.,
Schwartz J.R.,
Orrison B.M.,
Polymeropoulos M.H.,
Nussbaum R.L.;
"Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element.";
Genome Res. 11:78-86(2001).
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[6]
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NUCLEOTIDE SEQUENCE (ISOFORM 1).
Hu X.,
Xu Y.,
Peng X.,
Yuan J.,
Qiang B.;
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
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[7]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Ebert L.,
Schick M.,
Neubert P.,
Schatten R.,
Henze S.,
Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
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[8]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Livingston R.J.,
Rieder M.J.,
Shaffer T.,
Bertucci C.,
Baier C.N.,
Rajkumar N.,
Willa H.T.,
Daniels M.,
Downing T.K.,
Stanaway I.B.,
Nguyen C.P.,
Gildersleeve H.,
Cassidy C.M.,
Johnson E.J.,
Swanson J.E.,
McFarland I.,
Yool B.,
Park C.,
Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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[9]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Uterus;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[10]
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PHOSPHORYLATION BY CASEIN KINASE.
DOI=10.1074/jbc.275.1.390; PubMed=10617630 [NCBI, ExPASy, EBI, Israel, Japan]
Okochi M.,
Walter J.,
Koyama A.,
Nakajo S.,
Baba M.,
Iwatsubo T.,
Meijer L.,
Kahle P.J.,
Haass C.;
"Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein.";
J. Biol. Chem. 275:390-397(2000).
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[11]
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PHOSPHORYLATION BY G-PROTEIN COUPLED RECEPTOR KINASE.
DOI=10.1074/jbc.M003542200; PubMed=10852916 [NCBI, ExPASy, EBI, Israel, Japan]
Pronin A.N.,
Morris A.J.,
Surguchov A.,
Benovic J.L.;
"Synucleins are a novel class of substrates for G protein-coupled receptor kinases.";
J. Biol. Chem. 275:26515-26522(2000).
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[12]
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INTERACTION WITH PHOSPHOLIPASE D.
DOI=10.1074/jbc.M110414200; PubMed=11821392 [NCBI, ExPASy, EBI, Israel, Japan]
Ahn B.H.,
Rhim H.,
Kim S.Y.,
Sung Y.M.,
Lee M.Y.,
Choi J.Y.,
Wolozin B.,
Chang J.S.,
Lee Y.H.,
Kwon T.K.,
Chung K.C.,
Yoon S.H.,
Hahn S.J.,
Kim M.S.,
Jo Y.H.,
Min do S.;
"Alpha-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells.";
J. Biol. Chem. 277:12334-12342(2002).
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[13]
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INTERACTION WITH HISTONES, AND SUBCELLULAR LOCATION.
DOI=10.1021/bi0341152; PubMed=12859192 [NCBI, ExPASy, EBI, Israel, Japan]
Goers J.,
Manning-Bog A.B.,
McCormack A.L.,
Millett I.S.,
Doniach S.,
Di Monte D.A.,
Uversky V.N.,
Fink A.L.;
"Nuclear localization of alpha-synuclein and its interaction with histones.";
Biochemistry 42:8465-8471(2003).
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[14]
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ROLE OF THE C-TERMINUS IN FIBRILLOGENESIS.
DOI=10.1021/bi027363r; PubMed=12859200 [NCBI, ExPASy, EBI, Israel, Japan]
Murray I.V.,
Giasson B.I.,
Quinn S.M.,
Koppaka V.,
Axelsen P.H.,
Ischiropoulos H.,
Trojanowski J.Q.,
Lee V.M.;
"Role of alpha-synuclein carboxy-terminus on fibril formation in vitro.";
Biochemistry 42:8530-8540(2003).
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[15]
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REVIEW.
PubMed=12558071 [NCBI, ExPASy, EBI, Israel, Japan]
Alves da Costa C.;
"Recent advances on alpha-synuclein cell biology: functions and dysfunctions.";
Curr. Mol. Med. 3:17-24(2003).
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[16]
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MUTAGENESIS OF TYR-39; TYR-125; TYR-133 AND TYR-136, CHARACTERIZATION OF VARIANT THR-53, AND PHOSPHORYLATION AT TYR-125.
DOI=10.1074/jbc.M213217200; PubMed=12893833 [NCBI, ExPASy, EBI, Israel, Japan]
Takahashi T.,
Yamashita H.,
Nagano Y.,
Nakamura T.,
Ohmori H.,
Avraham H.,
Avraham S.,
Yasuda M.,
Matsumoto M.;
"Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation.";
J. Biol. Chem. 278:42225-42233(2003).
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[17]
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VARIANT PARK1 THR-53.
DOI=10.1126/science.276.5321.2045; PubMed=9197268 [NCBI, ExPASy, EBI, Israel, Japan]
Polymeropoulos M.H.,
Lavedan C.,
Leroy E.,
Ide S.E.,
Dehejia A.,
Dutra A.,
Pike B.,
Root H.,
Rubenstein J.,
Boyer R.,
Stenroos E.S.,
Chandrasekharappa S.,
Athanassiadou A.,
Papapetropoulos T.,
Johnson W.G.,
Lazzarini A.M.,
Duvoisin R.C.,
di Iorio G.,
Golbe L.I.,
Nussbaum R.L.;
"Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.";
Science 276:2045-2047(1997).
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[18]
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VARIANT PARK1 PRO-30.
DOI=10.1038/ng0298-106; PubMed=9462735 [NCBI, ExPASy, EBI, Israel, Japan]
Krueger R.,
Kuhn W.,
Mueller T.,
Woitalla D.,
Graeber M.,
Koesel S.,
Przuntek H.,
Epplen J.T.,
Schoels L.,
Riess O.;
"Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.";
Nat. Genet. 18:106-108(1998).
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[19]
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VARIANT PARK1/DLB LYS-46.
DOI=10.1002/ana.10795; PubMed=14755719 [NCBI, ExPASy, EBI, Israel, Japan]
Zarranz J.J.,
Alegre J.,
Gomez-Esteban J.C.,
Lezcano E.,
Ros R.,
Ampuero I.,
Vidal L.,
Hoenicka J.,
Rodriguez O.,
Atares B.,
Llorens V.,
Gomez Tortosa E.,
del Ser T.,
Munoz D.G.,
de Yebenes J.G.;
"The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.";
Ann. Neurol. 55:164-173(2004).
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[20]
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CHARACTERIZATION OF VARIANT LYS-46.
DOI=10.1016/j.febslet.2004.09.038; PubMed=15498564 [NCBI, ExPASy, EBI, Israel, Japan]
Choi W.,
Zibaee S.,
Jakes R.,
Serpell L.C.,
Davletov B.,
Crowther R.A.,
Goedert M.;
"Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein.";
FEBS Lett. 576:363-368(2004).
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- FUNCTION: May be involved in the regulation of dopamine release and transport. Soluble protein, normally localized primarily at the presynaptic region of axons, which can form filamentous aggregates that are the major non amyloid component of intracellular inclusions in several neurodegenerative diseases (synucleinopathies). Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase 3 activation.
- SUBUNIT: Soluble monomer which can form filamentous aggregates. Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones.
- SUBCELLULAR LOCATION: Cytoplasm. Membrane. Nucleus. Note=Membrane-bound in dopaminergic neurons. Also found in the nucleus.
- ALTERNATIVE PRODUCTS:
3 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.
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| Name | 2-4 |
| Synonyms | NACP112 |
| Isoform ID | P37840-2 |
| Features which should be applied to build the isoform sequence: VSP_006364. |
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| Name | 2-5 |
| Isoform ID | P37840-3 |
| Features which should be applied to build the isoform sequence: VSP_006363. |
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- TISSUE SPECIFICITY: Expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver. Concentrated in presynaptic nerve terminals.
- DOMAIN: The NAC domain is involved in the fibril formation. The middle region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments.
- PTM: Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress.
- PTM: Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.
- PTM: Ubiquitinated. The predominant conjugate is the diubiquitinated form (By similarity).
- DISEASE: Defects in SNCA are a cause of autosomal dominant Parkinson disease 1 (PARK1) [MIM:168601, 168600]. Parkinson disease (PD) is a complex, multifactorial disorder that typically manifests after the age of 50 years, although early-onset cases (before 50 years) are known. PD generally arises as a sporadic condition but is occasionally inherited as a simple mendelian trait. Although sporadic and familial PD are very similar, inherited forms of the disease usually begin at earlier ages and are associated with atypical clinical features. PD is characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
- DISEASE: Defects in SNCA are the cause of Parkinson disease 4 (PARK4) [MIM:605543, 168600].
- DISEASE: Defects in SNCA are the cause of Lewy body dementia (DLB) [MIM:127750]. DLB is a neurodegenerative disorder clinically characterized by dementia and parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Presence of Lewy bodies are the only essential pathologic features.
- DISEASE: Deposition of fibrillar amyloid proteins intraneuronally as neurofibrillary tangles is characteristic of Alzheimer disease (AD). SNCA is a minor protein found within these deposits, but a major non amyloid component.
- DISEASE: Brain iron accumulation type 1 (NBIA1, also called Hallervorden-Spatz syndrome), a rare neuroaxonal dystrophy, is histologically characterized by axonal spheroids, iron deposition, Lewy body (LB)-like intraneuronal inclusions, glial inclusions and neurofibrillary tangles. SNCA is found in LB-like inclusions, glial inclusions and spheroids.
- SIMILARITY: Belongs to the synuclein family.
- WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=SNCA";.
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