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Identification
HMDB Protein ID HMDBP02388
Secondary Accession Numbers
  • 7879
Name Alpha-synuclein
Synonyms
  1. NACP
  2. Non-A beta component of AD amyloid
  3. Non-A4 component of amyloid precursor
Gene Name SNCA
Protein Type Unknown
Biological Properties
General Function Involved in regulation of dopamine secretion
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular part
cytoplasm
Process
biological regulation
regulation of biological process
regulation of cellular process
regulation of dopamine secretion
regulation of cell communication
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Membrane
Gene Properties
Chromosome Location Chromosome:4
Locus 4q21
SNPs SNCA
Gene Sequence
>423 bp
ATGGATGTATTCATGAAAGGACTTTCAAAGGCCAAGGAGGGAGTTGTGGCTGCTGCTGAG
AAAACCAAACAGGGTGTGGCAGAAGCAGCAGGAAAGACAAAAGAGGGTGTTCTCTATGTA
GGCTCCAAAACCAAGGAGGGAGTGGTGCATGGTGTGGCAACAGTGGCTGAGAAGACCAAA
GAGCAAGTGACAAATGTTGGAGGAGCAGTGGTGACGGGTGTGACAGCAGTAGCCCAGAAG
ACAGTGGAGGGAGCAGGGAGCATTGCAGCAGCCACTGGCTTTGTCAAAAAGGACCAGTTG
GGCAAGAATGAAGAAGGAGCCCCACAGGAAGGAATTCTGGAAGATATGCCTGTGGATCCT
GACAATGAGGCTTATGAAATGCCTTCTGAGGAAGGGTATCAAGACTACGAACCTGAAGCC
TAA
Protein Properties
Number of Residues 140
Molecular Weight 14460.2
Theoretical pI 4.37
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Alpha-synuclein
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
DNEAYEMPSEEGYQDYEPEA
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P37840
UniProtKB/Swiss-Prot Entry Name SYUA_HUMAN
PDB IDs
GenBank Gene ID L08850
GeneCard ID SNCA
GenAtlas ID SNCA
HGNC ID HGNC:11138
References
General References
  1. 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. [PubMed:14702039 ]
  2. 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. [PubMed:15489334 ]
  3. 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. [PubMed:12893833 ]
  4. 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. [PubMed:8248242 ]
  5. 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. [PubMed:7601450 ]
  6. 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. [PubMed:7802671 ]
  7. 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. [PubMed:11156617 ]
  8. 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. [PubMed:10617630 ]
  9. 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. [PubMed:10852916 ]
  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. [PubMed:11821392 ]
  11. 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. [PubMed:12859192 ]
  12. 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. [PubMed:12859200 ]
  13. Alves da Costa C: Recent advances on alpha-synuclein cell biology: functions and dysfunctions. Curr Mol Med. 2003 Feb;3(1):17-24. [PubMed:12558071 ]
  14. 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. [PubMed:15615727 ]
  15. 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. [PubMed:9197268 ]
  16. 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. [PubMed:9462735 ]
  17. 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. [PubMed:14755719 ]
  18. 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. [PubMed:15498564 ]