Alpha-synuclein

NameAlpha-synuclein
Synonyms
  • NACP
  • Non-A beta component of AD amyloid
  • Non-A4 component of amyloid precursor
  • PARK1
Gene NameSNCA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001750|Alpha-synuclein
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
DNEAYEMPSEEGYQDYEPEA
Number of residues140
Molecular Weight14460.155
Theoretical pI4.37
GO Classification
Functions
  • phosphoprotein binding
  • ferrous iron binding
  • oxidoreductase activity
  • magnesium ion binding
  • zinc ion binding
  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process
  • tau protein binding
  • alpha-tubulin binding
  • Hsp70 protein binding
  • copper ion binding
  • calcium ion binding
  • kinesin binding
  • histone binding
  • dynein binding
  • identical protein binding
  • transcription regulatory region DNA binding
  • phospholipid binding
Processes
  • positive regulation of inositol phosphate biosynthetic process
  • cellular protein metabolic process
  • synapse organization
  • negative regulation of thrombin receptor signaling pathway
  • mitochondrial ATP synthesis coupled electron transport
  • protein destabilization
  • negative regulation of transporter activity
  • regulation of macrophage activation
  • response to iron(II) ion
  • oxidation-reduction process
  • neutral lipid metabolic process
  • positive regulation of glutathione peroxidase activity
  • fatty acid metabolic process
  • microglial cell activation
  • negative regulation of apoptotic process
  • positive regulation of hydrogen peroxide catabolic process
  • long-term synaptic potentiation
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • regulation of locomotion
  • regulation of acyl-CoA biosynthetic process
  • behavioral response to cocaine
  • negative regulation of exocytosis
  • negative regulation of microtubule polymerization
  • positive regulation of peptidyl-serine phosphorylation
  • regulation of glutamate secretion
  • response to interleukin-1
  • negative regulation of histone acetylation
  • positive regulation of release of sequestered calcium ion into cytosol
  • negative regulation of dopamine metabolic process
  • synaptic vesicle endocytosis
  • regulation of phospholipase activity
  • negative regulation of platelet-derived growth factor receptor signaling pathway
  • response to lipopolysaccharide
  • regulation of long-term neuronal synaptic plasticity
  • regulation of reactive oxygen species biosynthetic process
  • adult locomotory behavior
  • dopamine biosynthetic process
  • negative regulation of serotonin uptake
  • negative regulation of transcription from RNA polymerase II promoter
  • positive regulation of receptor recycling
  • response to interferon-gamma
  • dopamine uptake involved in synaptic transmission
  • regulation of synaptic vesicle recycling
  • cellular response to copper ion
  • extracellular fibril organization
  • positive regulation of neurotransmitter secretion
  • phospholipid metabolic process
  • response to magnesium ion
  • cellular response to oxidative stress
  • regulation of dopamine secretion
  • mitochondrial membrane organization
  • aging
  • positive regulation of endocytosis
  • positive regulation of apoptotic process
  • positive regulation of protein serine/threonine kinase activity
  • negative regulation of dopamine uptake involved in synaptic transmission
  • negative regulation of neuron apoptotic process
  • receptor internalization
  • response to drug
  • negative regulation of mitochondrial electron transport, NADH to ubiquinone
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • negative regulation of protein phosphorylation
  • negative regulation of monooxygenase activity
  • cellular response to epinephrine stimulus
  • cellular response to fibroblast growth factor stimulus
  • negative regulation of norepinephrine uptake
  • excitatory postsynaptic potential
Components
  • extracellular space
  • cytoplasmic vesicle membrane
  • axon
  • nuclear outer membrane
  • lysosome
  • fibril
  • rough endoplasmic reticulum
  • inclusion body
  • actin cytoskeleton
  • cytoplasm
  • synaptic vesicle
  • mitochondrion
  • cell junction
  • cell cortex
  • membrane
  • Golgi apparatus
  • cytosol
  • ribosome
  • growth cone
  • perinuclear region of cytoplasm
  • extracellular region
  • nucleus
  • plasma membrane
  • terminal bouton
General FunctionNot Available
Specific FunctionNot Available
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID437365
UniProtKB IDP37840
UniProtKB Entry NameSYUA_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021281|Alpha-synuclein (SNCA)
ATGGATGTATTCATGAAAGGACTTTCAAAGGCCAAGGAGGGAGTTGTGGCTGCTGCTGAG
AAAACCAAACAGGGTGTGGCAGAAGCAGCAGGAAAGACAAAAGAGGGTGTTCTCTATGTA
GGCTCCAAAACCAAGGAGGGAGTGGTGCATGGTGTGGCAACAGTGGCTGAGAAGACCAAA
GAGCAAGTGACAAATGTTGGAGGAGCAGTGGTGACGGGTGTGACAGCAGTAGCCCAGAAG
ACAGTGGAGGGAGCAGGGAGCATTGCAGCAGCCACTGGCTTTGTCAAAAAGGACCAGTTG
GGCAAGAATGAAGAAGGAGCCCCACAGGAAGGAATTCTGGAAGATATGCCTGTGGATCCT
GACAATGAGGCTTATGAAATGCCTTCTGAGGAAGGGTATCAAGACTACGAACCTGAAGCC
TAA
GenBank Gene IDL08850
GeneCard IDNot Available
GenAtlas IDSNCA
HGNC IDHGNC:11138
Chromosome LocationNot Available
Locus4q21
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. 8248242
  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. 7601450
  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. 7802671
  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. 11156617
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 10617630
  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. 10852916
  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. 11162638
  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. 11821392
  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. 11813001
  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. 12859192
  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. 12859200
  14. Alves da Costa C: Recent advances on alpha-synuclein cell biology: functions and dysfunctions. Curr Mol Med. 2003 Feb;3(1):17-24. 12558071
  15. 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. 2003 Oct 24;278(43):42225-33. Epub 2003 Jul 31. 12893833
  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. 15282274
  17. Waxman EA, Mazzulli JR, Giasson BI: Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization. Biochemistry. 2009 Oct 13;48(40):9427-36. doi: 10.1021/bi900539p. 19722699
  18. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  19. Dudzik CG, Walter ED, Millhauser GL: Coordination features and affinity of the Cu(2)+ site in the alpha-synuclein protein of Parkinson's disease. Biochemistry. 2011 Mar 22;50(11):1771-7. doi: 10.1021/bi101912q. Epub 2011 Feb 14. 21319811
  20. Trexler AJ, Rhoades E: N-Terminal acetylation is critical for forming alpha-helical oligomer of alpha-synuclein. Protein Sci. 2012 May;21(5):601-5. doi: 10.1002/pro.2056. Epub 2012 Mar 30. 22407793
  21. Ulmer TS, Bax A, Cole NB, Nussbaum RL: Structure and dynamics of micelle-bound human alpha-synuclein. J Biol Chem. 2005 Mar 11;280(10):9595-603. Epub 2004 Dec 22. 15615727
  22. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL: Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997 Jun 27;276(5321):2045-7. 9197268
  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. 9462735
  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. 14755719
  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. 15498564
  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. 23457019
  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. 23427326
  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. 24936070
  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. 25561023