Alpha-synuclein

Details

Name
Alpha-synuclein
Synonyms
  • NACP
  • Non-A beta component of AD amyloid
  • Non-A4 component of amyloid precursor
  • PARK1
Gene Name
SNCA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001750|Alpha-synuclein
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
DNEAYEMPSEEGYQDYEPEA
Number of residues
140
Molecular Weight
14460.155
Theoretical pI
4.37
GO Classification
Functions
alpha-tubulin binding / calcium ion binding / copper ion binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / dynein binding / ferrous iron binding / histone binding / Hsp70 protein binding / identical protein binding / kinesin binding / magnesium ion binding / oxidoreductase activity / phospholipid binding / phosphoprotein binding / tau protein binding / transcription regulatory region DNA binding / zinc ion binding
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / adult locomotory behavior / aging / behavioral response to cocaine / cellular protein metabolic process / cellular response to copper ion / cellular response to epinephrine stimulus / cellular response to fibroblast growth factor stimulus / cellular response to oxidative stress / dopamine biosynthetic process / dopamine uptake involved in synaptic transmission / excitatory postsynaptic potential / extracellular fibril organization / fatty acid metabolic process / long-term synaptic potentiation / microglial cell activation / mitochondrial ATP synthesis coupled electron transport / mitochondrial membrane organization / negative regulation of apoptotic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of dopamine metabolic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of exocytosis / negative regulation of histone acetylation / negative regulation of microtubule polymerization / negative regulation of mitochondrial electron transport, NADH to ubiquinone / negative regulation of monooxygenase activity / negative regulation of neuron apoptotic process / negative regulation of norepinephrine uptake / negative regulation of platelet-derived growth factor receptor signaling pathway / negative regulation of protein phosphorylation / negative regulation of serotonin uptake / negative regulation of thrombin receptor signaling pathway / negative regulation of transcription from RNA polymerase II promoter / negative regulation of transporter activity / neutral lipid metabolic process / oxidation-reduction process / phospholipid metabolic process / positive regulation of apoptotic process / positive regulation of endocytosis / positive regulation of glutathione peroxidase activity / positive regulation of hydrogen peroxide catabolic process / positive regulation of inositol phosphate biosynthetic process / positive regulation of neurotransmitter secretion / positive regulation of peptidyl-serine phosphorylation / positive regulation of protein serine/threonine kinase activity / positive regulation of receptor recycling / positive regulation of release of sequestered calcium ion into cytosol / protein destabilization / receptor internalization / regulation of acyl-CoA biosynthetic process / regulation of dopamine secretion / regulation of glutamate secretion / regulation of locomotion / regulation of long-term neuronal synaptic plasticity / regulation of macrophage activation / regulation of phospholipase activity / regulation of reactive oxygen species biosynthetic process / regulation of synaptic vesicle recycling / response to drug / response to interferon-gamma / response to interleukin-1 / response to iron(II) ion / response to lipopolysaccharide / response to magnesium ion / synapse organization / synaptic vesicle endocytosis
Components
actin cytoskeleton / axon / cell cortex / cell junction / cytoplasm / cytoplasmic vesicle membrane / cytosol / extracellular region / extracellular space / fibril / Golgi apparatus / growth cone / inclusion body / lysosome / membrane / mitochondrion / nuclear outer membrane / nucleus / perinuclear region of cytoplasm / plasma membrane / ribosome / rough endoplasmic reticulum / synaptic vesicle / terminal bouton
General Function
Not Available
Specific Function
Not Available
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021281|Alpha-synuclein (SNCA)
ATGGATGTATTCATGAAAGGACTTTCAAAGGCCAAGGAGGGAGTTGTGGCTGCTGCTGAG
AAAACCAAACAGGGTGTGGCAGAAGCAGCAGGAAAGACAAAAGAGGGTGTTCTCTATGTA
GGCTCCAAAACCAAGGAGGGAGTGGTGCATGGTGTGGCAACAGTGGCTGAGAAGACCAAA
GAGCAAGTGACAAATGTTGGAGGAGCAGTGGTGACGGGTGTGACAGCAGTAGCCCAGAAG
ACAGTGGAGGGAGCAGGGAGCATTGCAGCAGCCACTGGCTTTGTCAAAAAGGACCAGTTG
GGCAAGAATGAAGAAGGAGCCCCACAGGAAGGAATTCTGGAAGATATGCCTGTGGATCCT
GACAATGAGGCTTATGAAATGCCTTCTGAGGAAGGGTATCAAGACTACGAACCTGAAGCC
TAA
Chromosome Location
Not Available
Locus
4q21
External Identifiers
ResourceLink
UniProtKB IDP37840
UniProtKB Entry NameSYUA_HUMAN
GenBank Protein ID437365
GenBank Gene IDL08850
GenAtlas IDSNCA
HGNC IDHGNC:11138
General References
  1. Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, 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. 1993 Dec 1;90(23):11282-6. [Article]
  2. Campion D, Martin C, Heilig R, Charbonnier F, Moreau V, Flaman JM, Petit JL, Hannequin D, Brice A, Frebourg T: The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease. Genomics. 1995 Mar 20;26(2):254-7. [Article]
  3. 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. 1994 Dec 15;205(2):1366-72. [Article]
  4. Touchman JW, Dehejia A, Chiba-Falek O, Cabin DE, Schwartz JR, Orrison BM, Polymeropoulos MH, Nussbaum RL: Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element. Genome Res. 2001 Jan;11(1):78-86. [Article]
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  7. Okochi M, Walter J, Koyama A, Nakajo S, Baba M, Iwatsubo T, Meijer L, Kahle PJ, Haass C: Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J Biol Chem. 2000 Jan 7;275(1):390-7. [Article]
  8. Pronin AN, Morris AJ, Surguchov A, Benovic JL: Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem. 2000 Aug 25;275(34):26515-22. [Article]
  9. Nakamura T, Yamashita H, Takahashi T, Nakamura S: Activated Fyn phosphorylates alpha-synuclein at tyrosine residue 125. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1085-92. [Article]
  10. Ahn BH, Rhim H, Kim SY, Sung YM, Lee MY, Choi JY, Wolozin B, Chang JS, Lee YH, Kwon TK, Chung KC, Yoon SH, Hahn SJ, Kim MS, Jo YH, Min DS: alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells. J Biol Chem. 2002 Apr 5;277(14):12334-42. Epub 2002 Jan 30. [Article]
  11. Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T: alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol. 2002 Feb;4(2):160-4. [Article]
  12. Goers J, Manning-Bog AB, McCormack AL, Millett IS, Doniach S, Di Monte DA, Uversky VN, Fink AL: Nuclear localization of alpha-synuclein and its interaction with histones. Biochemistry. 2003 Jul 22;42(28):8465-71. [Article]
  13. Murray IV, Giasson BI, Quinn SM, Koppaka V, Axelsen PH, Ischiropoulos H, Trojanowski JQ, Lee VM: Role of alpha-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry. 2003 Jul 22;42(28):8530-40. [Article]
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  16. Fortin DL, Troyer MD, Nakamura K, Kubo S, Anthony MD, Edwards RH: Lipid rafts mediate the synaptic localization of alpha-synuclein. J Neurosci. 2004 Jul 28;24(30):6715-23. [Article]
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  23. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O: Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 1998 Feb;18(2):106-8. [Article]
  24. Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG: The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164-73. [Article]
  25. Choi W, Zibaee S, Jakes R, Serpell LC, Davletov B, Crowther RA, Goedert M: Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein. FEBS Lett. 2004 Oct 22;576(3):363-8. [Article]
  26. Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, Sherman H, Yu I, Shah B, Weir D, Thompson C, Szu-Tu C, Trinh J, Aasly JO, Rajput A, Rajput AH, Jon Stoessl A, Farrer MJ: Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease. Mov Disord. 2013 Jun;28(6):811-3. doi: 10.1002/mds.25421. Epub 2013 Mar 1. [Article]
  27. Proukakis C, Dudzik CG, Brier T, MacKay DS, Cooper JM, Millhauser GL, Houlden H, Schapira AH: A novel alpha-synuclein missense mutation in Parkinson disease. Neurology. 2013 Mar 12;80(11):1062-4. doi: 10.1212/WNL.0b013e31828727ba. Epub 2013 Feb 20. [Article]
  28. Khalaf O, Fauvet B, Oueslati A, Dikiy I, Mahul-Mellier AL, Ruggeri FS, Mbefo MK, Vercruysse F, Dietler G, Lee SJ, Eliezer D, Lashuel HA: The H50Q mutation enhances alpha-synuclein aggregation, secretion, and toxicity. J Biol Chem. 2014 Aug 8;289(32):21856-76. doi: 10.1074/jbc.M114.553297. Epub 2014 Jun 16. [Article]
  29. Tsigelny IF, Sharikov Y, Kouznetsova VL, Greenberg JP, Wrasidlo W, Overk C, Gonzalez T, Trejo M, Spencer B, Kosberg K, Masliah E: Molecular determinants of alpha-synuclein mutants' oligomerization and membrane interactions. ACS Chem Neurosci. 2015 Mar 18;6(3):403-16. doi: 10.1021/cn500332w. Epub 2015 Jan 21. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02709ResveratrolinvestigationalunknownDetails
DB09130Copperapproved, investigationalunknownDetails
DB04209Dequaliniumapproved, investigationalunknownmodulatorDetails