ID SYUA_HUMAN Reviewed; 140 AA. AC P37840; A8K2A4; Q13701; Q4JHI3; Q6IAU6; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 04-NOV-2026, entry version 262. DE RecName: Full=Alpha-synuclein; DE AltName: Full=Non-A beta component of AD amyloid; DE AltName: Full=Non-A4 component of amyloid precursor; DE Short=NACP; GN Name=SNCA; Synonyms=NACP, PARK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 61-95. RC TISSUE=Brain; RX PubMed=8248242; DOI=10.1073/pnas.90.23.11282; RA Ueda K., Fukushima H., Masliah E., Xia Y., Iwai A., Yoshimoto M., RA Otero D.A., Kondo J., Ihara Y., Saitoh T.; RT "Molecular cloning of cDNA encoding an unrecognized component of amyloid in RT Alzheimer disease."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11282-11286(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2-4 AND 2-5). RX PubMed=7601450; DOI=10.1016/0888-7543(95)80208-4; RA Campion D., Martin C., Heilig R., Charbonnier F., Moreau V., Flaman J.-M., RA Petit J.-L., Hannequin D., Brice A., Frebourg T.; RT "The NACP/synuclein gene: chromosomal assignment and screening for RT alterations in Alzheimer disease."; RL Genomics 26:254-257(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2-4). RC TISSUE=Brain; RX PubMed=7802671; DOI=10.1006/bbrc.1994.2816; RA Ueda K., Saitoh T., Mori H.; RT "Tissue-dependent alternative splicing of mRNA for NACP, the precursor of RT non-A beta component of Alzheimer's disease amyloid."; RL Biochem. Biophys. Res. Commun. 205:1366-1372(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Xia Y., Silva R.D., Chen X.H., Saitoh T.; RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2-4). RX PubMed=11156617; DOI=10.1101/gr.165801; RA Touchman J.W., Dehejia A., Chiba-Falek O., Cabin D.E., Schwartz J.R., RA Orrison B.M., Polymeropoulos M.H., Nussbaum R.L.; RT "Human and mouse alpha-synuclein genes: comparative genomic sequence RT analysis and identification of a novel gene regulatory element."; RL Genome Res. 11:78-86(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Hu X., Xu Y., Peng X., Yuan J., Qiang B.; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP PROTEIN SEQUENCE OF 59-96, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Fetal brain cortex; RA Lubec G., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [13] RP TISSUE SPECIFICITY. RX PubMed=8194594; DOI=10.1016/0014-5793(94)00395-5; RA Jakes R., Spillantini M.G., Goedert M.; RT "Identification of two distinct synucleins from human brain."; RL FEBS Lett. 345:27-32(1994). RN [14] RP PHOSPHORYLATION AT SER-87 AND SER-129 BY CK1 AND CK2. RX PubMed=10617630; DOI=10.1074/jbc.275.1.390; RA Okochi M., Walter J., Koyama A., Nakajo S., Baba M., Iwatsubo T., RA Meijer L., Kahle P.J., Haass C.; RT "Constitutive phosphorylation of the Parkinson's disease associated alpha- RT synuclein."; RL J. Biol. Chem. 275:390-397(2000). RN [15] RP PHOSPHORYLATION BY G PROTEIN-COUPLED RECEPTOR KINASE. RX PubMed=10852916; DOI=10.1074/jbc.m003542200; RA Pronin A.N., Morris A.J., Surguchov A., Benovic J.L.; RT "Synucleins are a novel class of substrates for G protein-coupled receptor RT kinases."; RL J. Biol. Chem. 275:26515-26522(2000). RN [16] RP PHOSPHORYLATION AT TYR-125 BY FYN. RX PubMed=11162638; DOI=10.1006/bbrc.2000.4253; RA Nakamura T., Yamashita H., Takahashi T., Nakamura S.; RT "Activated Fyn phosphorylates alpha-synuclein at tyrosine residue 125."; RL Biochem. Biophys. Res. Commun. 280:1085-1092(2001). RN [17] RP INTERACTION WITH PHOSPHOLIPASE D. RX PubMed=11821392; DOI=10.1074/jbc.m110414200; RA Ahn B.H., Rhim H., Kim S.Y., Sung Y.M., Lee M.Y., Choi J.Y., Wolozin B., RA Chang J.S., Lee Y.H., Kwon T.K., Chung K.C., Yoon S.H., Hahn S.J., RA Kim M.S., Jo Y.H., Min do S.; RT "Alpha-synuclein interacts with phospholipase D isozymes and inhibits RT pervanadate-induced phospholipase D activation in human embryonic kidney- RT 293 cells."; RL J. Biol. Chem. 277:12334-12342(2002). RN [18] RP PHOSPHORYLATION AT SER-129. RX PubMed=11813001; DOI=10.1038/ncb748; RA Fujiwara H., Hasegawa M., Dohmae N., Kawashima A., Masliah E., RA Goldberg M.S., Shen J., Takio K., Iwatsubo T.; RT "alpha-Synuclein is phosphorylated in synucleinopathy lesions."; RL Nat. Cell Biol. 4:160-164(2002). RN [19] RP INTERACTION WITH HISTONES, AND SUBCELLULAR LOCATION. RX PubMed=12859192; DOI=10.1021/bi0341152; RA Goers J., Manning-Bog A.B., McCormack A.L., Millett I.S., Doniach S., RA Di Monte D.A., Uversky V.N., Fink A.L.; RT "Nuclear localization of alpha-synuclein and its interaction with RT histones."; RL Biochemistry 42:8465-8471(2003). RN [20] RP ROLE OF THE C-TERMINUS IN FIBRILLOGENESIS. RX PubMed=12859200; DOI=10.1021/bi027363r; RA Murray I.V., Giasson B.I., Quinn S.M., Koppaka V., Axelsen P.H., RA Ischiropoulos H., Trojanowski J.Q., Lee V.M.; RT "Role of alpha-synuclein carboxy-terminus on fibril formation in vitro."; RL Biochemistry 42:8530-8540(2003). RN [21] RP REVIEW. RX PubMed=12558071; DOI=10.2174/1566524033361690; RA Alves da Costa C.; RT "Recent advances on alpha-synuclein cell biology: functions and RT dysfunctions."; RL Curr. Mol. Med. 3:17-24(2003). RN [22] RP MUTAGENESIS OF TYR-39; TYR-125; TYR-133 AND TYR-136, CHARACTERIZATION OF RP VARIANT THR-53, AND PHOSPHORYLATION AT TYR-125. RX PubMed=12893833; DOI=10.1074/jbc.m213217200; RA Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., RA Avraham S., Yasuda M., Matsumoto M.; RT "Identification and characterization of a novel Pyk2/related adhesion focal RT tyrosine kinase-associated protein that inhibits alpha-synuclein RT phosphorylation."; RL J. Biol. Chem. 278:42225-42233(2003). RN [23] RP INTERACTION WITH RPH3A AND RAB3A. RX PubMed=15207266; DOI=10.1016/j.nbd.2004.01.001; RA Dalfo E., Barrachina M., Rosa J.L., Ambrosio S., Ferrer I.; RT "Abnormal alpha-synuclein interactions with rab3a and rabphilin in diffuse RT Lewy body disease."; RL Neurobiol. Dis. 16:92-97(2004). RN [24] RP SUBCELLULAR LOCATION. RX PubMed=15282274; DOI=10.1523/jneurosci.1594-04.2004; RA Fortin D.L., Troyer M.D., Nakamura K., Kubo S., Anthony M.D., Edwards R.H.; RT "Lipid rafts mediate the synaptic localization of alpha-synuclein."; RL J. Neurosci. 24:6715-6723(2004). RN [25] RP FIBRILS FORMATION, DOMAIN NAC, AND MUTAGENESIS OF 67-GLY--VAL-71; RP 71-VAL--VAL-82; 76-ALA-VAL-77; VAL-77; ALA-78 AND 85-ALA--PHE-94. RX PubMed=19722699; DOI=10.1021/bi900539p; RA Waxman E.A., Mazzulli J.R., Giasson B.I.; RT "Characterization of hydrophobic residue requirements for alpha-synuclein RT fibrillization."; RL Biochemistry 48:9427-9436(2009). RN [26] RP FUNCTION, AND INTERACTION WITH VAMP2 AND SNAP25. RX PubMed=20798282; DOI=10.1126/science.1195227; RA Burre J., Sharma M., Tsetsenis T., Buchman V., Etherton M.R., Suedhof T.C.; RT "Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro."; RL Science 329:1663-1667(2010). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [28] RP COPPER-BINDING, AND MUTAGENESIS OF ASP-2 AND HIS-50. RX PubMed=21319811; DOI=10.1021/bi101912q; RA Dudzik C.G., Walter E.D., Millhauser G.L.; RT "Coordination features and affinity of the Cu(2)+ site in the alpha- RT synuclein protein of Parkinson's disease."; RL Biochemistry 50:1771-1777(2011). RN [29] RP SUBUNIT. RX PubMed=21841800; DOI=10.1038/nature10324; RA Bartels T., Choi J.G., Selkoe D.J.; RT "alpha-Synuclein occurs physiologically as a helically folded tetramer that RT resists aggregation."; RL Nature 477:107-110(2011). RN [30] RP INTERACTION WITH SERF1A. RX PubMed=22854022; DOI=10.1016/j.celrep.2012.06.012; RA Falsone S.F., Meyer N.H., Schrank E., Leitinger G., Pham C.L., RA Fodero-Tavoletti M.T., Holmberg M., Dulle M., Scicluna B., Gesslbauer B., RA Rueckert H.M., Wagner G.E., Merle D.A., Nollen E.A., Kungl A.J., Hill A.F., RA Cappai R., Zangger K.; RT "SERF protein is a direct modifier of amyloid fiber assembly."; RL Cell Rep. 2:358-371(2012). RN [31] RP ACETYLATION AT MET-1. RX PubMed=22407793; DOI=10.1002/pro.2056; RA Trexler A.J., Rhoades E.; RT "N-Terminal acetylation is critical for forming alpha-helical oligomer of RT alpha-synuclein."; RL Protein Sci. 21:601-605(2012). RN [32] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SLC6A3. RX PubMed=26442590; DOI=10.1074/jbc.m115.691592; RA Butler B., Saha K., Rana T., Becker J.P., Sambo D., Davari P., RA Goodwin J.S., Khoshbouei H.; RT "Dopamine Transporter Activity Is Modulated by alpha-Synuclein."; RL J. Biol. Chem. 290:29542-29554(2015). RN [33] RP INTERACTION WITH STXBP1, AND SUBCELLULAR LOCATION. RX PubMed=27597756; DOI=10.1083/jcb.201512016; RA Chai Y.J., Sierecki E., Tomatis V.M., Gormal R.S., Giles N., Morrow I.C., RA Xia D., Goetz J., Parton R.G., Collins B.M., Gambin Y., Meunier F.A.; RT "Munc18-1 is a molecular chaperone for alpha-synuclein, controlling its RT self-replicating aggregation."; RL J. Cell Biol. 214:705-718(2016). RN [34] RP FUNCTION. RX PubMed=28288128; DOI=10.1038/nn.4529; RA Logan T., Bendor J., Toupin C., Thorn K., Edwards R.H.; RT "alpha-Synuclein promotes dilation of the exocytotic fusion pore."; RL Nat. Neurosci. 20:681-689(2017). RN [35] RP FUNCTION. RX PubMed=30404828; DOI=10.1242/jcs.213017; RA Huang C.C., Chiu T.Y., Lee T.Y., Hsieh H.J., Lin C.C., Kao L.S.; RT "Soluble alpha-synuclein facilitates priming and fusion by releasing Ca2+ RT from the thapsigargin-sensitive Ca2+ pool in PC12 cells."; RL J. Cell Sci. 131:0-0(2018). RN [36] RP INTERACTION WITH DDX10, AND SUBCELLULAR LOCATION. RX PubMed=33657088; DOI=10.1371/journal.pgen.1009407; RA Popova B., Wang D., Paetz C., Akkermann D., Lazaro D.F., Galka D., RA Kolog Gulko M., Bohnsack M.T., Moebius W., Bohnsack K.E., Outeiro T.F., RA Braus G.H.; RT "DEAD-box RNA helicase Dbp4/DDX10 is an enhancer of alpha-synuclein RT toxicity and oligomerization."; RL PLoS Genet. 17:e1009407-e1009407(2021). RN [37] RP INTERACTION WITH SERF1A, AND SUBCELLULAR LOCATION. RX PubMed=31034892; DOI=10.1016/j.jmb.2019.04.031; RA Merle D.A., Witternigg A., Tam-Amersdorfer C., Hartlmueller C., RA Spreitzer E., Schrank E., Wagner-Lichtenegger S., Werzer O., Zangger K., RA Kungl A.J., Madl T., Meyer N.H., Falsone S.F.; RT "Increased Aggregation Tendency of Alpha-Synuclein in a Fully Disordered RT Protein Complex."; RL J. Mol. Biol. 431:2581-2598(2019). RN [38] RP STRUCTURE BY NMR IN COMPLEX WITH DETERGENT MICELLES. RX PubMed=15615727; DOI=10.1074/jbc.m411805200; RA Ulmer T.S., Bax A., Cole N.B., Nussbaum R.L.; RT "Structure and dynamics of micelle-bound human alpha-synuclein."; RL J. Biol. Chem. 280:9595-9603(2005). RN [39] RP STRUCTURE BY NMR OF 1-12, INTERACTION WITH SNCAIP, AND SUBCELLULAR RP LOCATION. RX PubMed=19762560; DOI=10.1096/fj.09-133082; RA Xie Y.Y., Zhou C.J., Zhou Z.R., Hong J., Che M.X., Fu Q.S., Song A.X., RA Lin D.H., Hu H.Y.; RT "Interaction with synphilin-1 promotes inclusion formation of alpha- RT synuclein: mechanistic insights and pathological implication."; RL FASEB J. 24:196-205(2010). RN [40] RP X-RAY CRYSTALLOGRAPHY AND 58-79. RX PubMed=21462277; DOI=10.1002/pro.630; RA Zhao M., Cascio D., Sawaya M.R., Eisenberg D.; RT "Structures of segments of alpha-synuclein fused to maltose-binding protein RT suggest intermediate states during amyloid formation."; RL Protein Sci. 20:996-1004(2011). RN [41] RP STRUCTURE BY NMR OF 1-19, AND INTERACTION WITH CALM1. RX PubMed=23607618; DOI=10.1021/bi400199p; RA Gruschus J.M., Yap T.L., Pistolesi S., Maltsev A.S., Lee J.C.; RT "NMR structure of calmodulin complexed to an N-terminally acetylated alpha- RT synuclein peptide."; RL Biochemistry 52:3436-3445(2013). RN [42] RP STRUCTURE BY ELECTRON MICROSCOPY AND 68-78. RX PubMed=26352473; DOI=10.1038/nature15368; RA Rodriguez J.A., Ivanova M.I., Sawaya M.R., Cascio D., Reyes F.E., Shi D., RA Sangwan S., Guenther E.L., Johnson L.M., Zhang M., Jiang L., Arbing M.A., RA Nannenga B.L., Hattne J., Whitelegge J., Brewster A.S., Messerschmidt M., RA Boutet S., Sauter N.K., Gonen T., Eisenberg D.S.; RT "Structure of the toxic core of alpha-synuclein from invisible crystals."; RL Nature 525:486-490(2015). RN [43] RP STRUCTURE BY NMR. RX PubMed=27018801; DOI=10.1038/nsmb.3194; RA Tuttle M.D., Comellas G., Nieuwkoop A.J., Covell D.J., Berthold D.A., RA Kloepper K.D., Courtney J.M., Kim J.K., Barclay A.M., Kendall A., Wan W., RA Stubbs G., Schwieters C.D., Lee V.M., George J.M., Rienstra C.M.; RT "Solid-state NMR structure of a pathogenic fibril of full-length human RT alpha-synuclein."; RL Nat. Struct. Mol. Biol. 23:409-415(2016). RN [44] RP STRUCTURE BY ELECTRON MICROSCOPY. RX PubMed=30190461; DOI=10.1038/s41467-018-05971-2; RA Li B., Ge P., Murray K.A., Sheth P., Zhang M., Nair G., Sawaya M.R., RA Shin W.S., Boyer D.R., Ye S., Eisenberg D.S., Zhou Z.H., Jiang L.; RT "Cryo-EM of full-length alpha-synuclein reveals fibril polymorphs with a RT common structural kernel."; RL Nat. Commun. 9:3609-3609(2018). RN [45] RP VARIANT PARK1 THR-53. RX PubMed=9197268; DOI=10.1126/science.276.5321.2045; RA Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., RA Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., RA Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., RA Lazzarini A.M., Duvoisin R.C., di Iorio G., Golbe L.I., Nussbaum R.L.; RT "Mutation in the alpha-synuclein gene identified in families with RT Parkinson's disease."; RL Science 276:2045-2047(1997). RN [46] RP VARIANT PARK1 PRO-30. RX PubMed=9462735; DOI=10.1038/ng0298-106; RA Krueger R., Kuhn W., Mueller T., Woitalla D., Graeber M., Koesel S., RA Przuntek H., Epplen J.T., Schoels L., Riess O.; RT "Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's RT disease."; RL Nat. Genet. 18:106-108(1998). RN [47] RP VARIANT PARK1/DLB LYS-46. RX PubMed=14755719; DOI=10.1002/ana.10795; RA Zarranz J.J., Alegre J., Gomez-Esteban J.C., Lezcano E., Ros R., RA Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atares B., Llorens V., RA Gomez Tortosa E., del Ser T., Munoz D.G., de Yebenes J.G.; RT "The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body RT dementia."; RL Ann. Neurol. 55:164-173(2004). RN [48] RP CHARACTERIZATION OF VARIANT LYS-46. RX PubMed=15498564; DOI=10.1016/j.febslet.2004.09.038; RA Choi W., Zibaee S., Jakes R., Serpell L.C., Davletov B., Crowther R.A., RA Goedert M.; RT "Mutation E46K increases phospholipid binding and assembly into filaments RT of human alpha-synuclein."; RL FEBS Lett. 576:363-368(2004). RN [49] RP VARIANT PARK1 GLN-50. RX PubMed=23457019; DOI=10.1002/mds.25421; RA Appel-Cresswell S., Vilarino-Guell C., Encarnacion M., Sherman H., Yu I., RA Shah B., Weir D., Thompson C., Szu-Tu C., Trinh J., Aasly J.O., Rajput A., RA Rajput A.H., Jon Stoessl A., Farrer M.J.; RT "Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's RT disease."; RL Mov. Disord. 28:811-813(2013). RN [50] RP VARIANT PARK1 GLN-50, AND CHARACTERIZATION OF VARIANT PARK1 GLN-50. RX PubMed=23427326; DOI=10.1212/wnl.0b013e31828727ba; RA Proukakis C., Dudzik C.G., Brier T., MacKay D.S., Cooper J.M., RA Millhauser G.L., Houlden H., Schapira A.H.; RT "A novel alpha-synuclein missense mutation in Parkinson disease."; RL Neurology 80:1062-1064(2013). RN [51] RP CHARACTERIZATION OF VARIANT PARK1 GLN-50, SUBCELLULAR LOCATION, SUBUNIT, RP AND PHOSPHORYLATION AT SER-129. RX PubMed=24936070; DOI=10.1074/jbc.m114.553297; RA Khalaf O., Fauvet B., Oueslati A., Dikiy I., Mahul-Mellier A.L., RA Ruggeri F.S., Mbefo M.K., Vercruysse F., Dietler G., Lee S.J., Eliezer D., RA Lashuel H.A.; RT "The H50Q mutation enhances alpha-synuclein aggregation, secretion, and RT toxicity."; RL J. Biol. Chem. 289:21856-21876(2014). RN [52] RP CHARACTERIZATION OF VARIANTS PARK1 PRO-30; LYS-46; GLN-50 AND THR-53, RP MUTAGENESIS OF GLU-35 AND GLU-57, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=25561023; DOI=10.1021/cn500332w; RA Tsigelny I.F., Sharikov Y., Kouznetsova V.L., Greenberg J.P., Wrasidlo W., RA Overk C., Gonzalez T., Trejo M., Spencer B., Kosberg K., Masliah E.; RT "Molecular determinants of alpha-synuclein mutants' oligomerization and RT membrane interactions."; RL ACS Chem. Neurosci. 6:403-416(2015). CC -!- FUNCTION: Neuronal protein that plays several roles in synaptic CC activity such as regulation of synaptic vesicle trafficking and CC subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, CC PubMed:28288128, PubMed:30404828). Participates as a monomer in CC synaptic vesicle exocytosis by enhancing vesicle priming, fusion and CC dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). CC Mechanistically, acts by increasing local Ca(2+) release from CC microdomains which is essential for the enhancement of ATP-induced CC exocytosis (PubMed:30404828). Also acts as a molecular chaperone in its CC multimeric membrane-bound state, assisting in the folding of synaptic CC fusion components called SNAREs (Soluble NSF Attachment Protein CC REceptors) at presynaptic plasma membrane in conjunction with cysteine CC string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity CC is important to sustain normal SNARE-complex assembly during aging CC (PubMed:20798282). Also plays a role in the regulation of the dopamine CC neurotransmission by associating with the dopamine transporter (DAT1) CC and thereby modulating its activity (PubMed:26442590). CC {ECO:0000269|PubMed:20798282, ECO:0000269|PubMed:26442590, CC ECO:0000269|PubMed:28288128, ECO:0000269|PubMed:30404828}. CC -!- SUBUNIT: Soluble monomer. Homotetramer (PubMed:21841800). A dynamic CC intracellular population of tetramers and monomers coexists normally CC and the tetramer plays an essential role in maintaining homeostasis CC (PubMed:21841800). Interacts with UCHL1 (By similarity). Interacts with CC phospholipase D and histones. Interacts (via N-terminus) with CC synphilin-1/SNCAIP; this interaction promotes formation of SNCA CC inclusions in the cytoplasm (PubMed:19762560). Interacts with CALM1 CC (PubMed:23607618). Interacts with STXBP1; this interaction controls CC SNCA self-replicating aggregation (PubMed:27597756). Interacts with CC SNARE components VAMP2 and SNAP25; these interactions allows SNARE CC complex assembly and integrity (PubMed:20798282). Interacts with RPH3A CC and RAB3A (PubMed:15207266). Interacts with SERF1A; this interaction CC promotes the aggregation of SNCA (PubMed:22854022, PubMed:31034892). CC Interacts with SEPTIN4 (By similarity). Interacts with DDX10; this CC interaction causes DDX10 mislocalization to the nucleoplasm and CC cytoplasmic inclusions (PubMed:33657088). CC {ECO:0000250|UniProtKB:O55042, ECO:0000250|UniProtKB:P37377, CC ECO:0000269|PubMed:15207266, ECO:0000269|PubMed:19762560, CC ECO:0000269|PubMed:20798282, ECO:0000269|PubMed:21841800, CC ECO:0000269|PubMed:22854022, ECO:0000269|PubMed:23607618, CC ECO:0000269|PubMed:27597756, ECO:0000269|PubMed:31034892, CC ECO:0000269|PubMed:33657088}. CC -!- INTERACTION: CC P37840; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-985879, EBI-22011868; CC P37840; P00519: ABL1; NbExp=3; IntAct=EBI-985879, EBI-375543; CC P37840; P00519-1: ABL1; NbExp=6; IntAct=EBI-985879, EBI-5278159; CC P37840; P00519-2: ABL1; NbExp=5; IntAct=EBI-985879, EBI-9254597; CC P37840; Q6ZTN6-2: ANKRD13D; NbExp=3; IntAct=EBI-985879, EBI-25840993; CC P37840; P63010-2: AP2B1; NbExp=3; IntAct=EBI-985879, EBI-11529439; CC P37840; O00203: AP3B1; NbExp=3; IntAct=EBI-985879, EBI-1044383; CC P37840; P02647: APOA1; NbExp=3; IntAct=EBI-985879, EBI-701692; CC P37840; P02649: APOE; NbExp=11; IntAct=EBI-985879, EBI-1222467; CC P37840; P05067: APP; NbExp=6; IntAct=EBI-985879, EBI-77613; CC P37840; Q8N6T3-3: ARFGAP1; NbExp=3; IntAct=EBI-985879, EBI-10694449; CC P37840; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-985879, EBI-2875816; CC P37840; Q0P5N6: ARL16; NbExp=3; IntAct=EBI-985879, EBI-10186132; CC P37840; Q8WXK3: ASB13; NbExp=3; IntAct=EBI-985879, EBI-707573; CC P37840; P18847: ATF3; NbExp=3; IntAct=EBI-985879, EBI-712767; CC P37840; Q9H0Y0: ATG10; NbExp=3; IntAct=EBI-985879, EBI-1048913; CC P37840; P46379-2: BAG6; NbExp=3; IntAct=EBI-985879, EBI-10988864; CC P37840; Q07812: BAX; NbExp=4; IntAct=EBI-985879, EBI-516580; CC P37840; Q07817: BCL2L1; NbExp=3; IntAct=EBI-985879, EBI-78035; CC P37840; O15392: BIRC5; NbExp=3; IntAct=EBI-985879, EBI-518823; CC P37840; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-985879, EBI-2837444; CC P37840; Q5SZD1: C6orf141; NbExp=3; IntAct=EBI-985879, EBI-10697767; CC P37840; P62158: CALM3; NbExp=3; IntAct=EBI-985879, EBI-397435; CC P37840; Q8N5S9-2: CAMKK1; NbExp=3; IntAct=EBI-985879, EBI-25850646; CC P37840; P55212: CASP6; NbExp=3; IntAct=EBI-985879, EBI-718729; CC P37840; Q7Z7K6: CENPV; NbExp=4; IntAct=EBI-985879, EBI-1210604; CC P37840; Q9HD42: CHMP1A; NbExp=3; IntAct=EBI-985879, EBI-1057156; CC P37840; Q16740: CLPP; NbExp=3; IntAct=EBI-985879, EBI-1056029; CC P37840; P10909: CLU; NbExp=4; IntAct=EBI-985879, EBI-1104674; CC P37840; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-985879, EBI-350590; CC P37840; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-985879, EBI-2872414; CC P37840; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-985879, EBI-9087876; CC P37840; P99999: CYCS; NbExp=3; IntAct=EBI-985879, EBI-446479; CC P37840; O75398: DEAF1; NbExp=3; IntAct=EBI-985879, EBI-718185; CC P37840; Q8NDP9: DKFZp547K2416; NbExp=3; IntAct=EBI-985879, EBI-25842538; CC P37840; O60479: DLX3; NbExp=3; IntAct=EBI-985879, EBI-3908248; CC P37840; A0AVK6: E2F8; NbExp=3; IntAct=EBI-985879, EBI-7779316; CC P37840; O75530-2: EED; NbExp=3; IntAct=EBI-985879, EBI-11132357; CC P37840; O00472: ELL2; NbExp=3; IntAct=EBI-985879, EBI-395274; CC P37840; Q8TC29: ENKUR; NbExp=3; IntAct=EBI-985879, EBI-9246952; CC P37840; O00471: EXOC5; NbExp=3; IntAct=EBI-985879, EBI-949824; CC P37840; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-985879, EBI-396453; CC P37840; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-985879, EBI-10226858; CC P37840; Q6PIV2: FOXR1; NbExp=3; IntAct=EBI-985879, EBI-10253815; CC P37840; P02792: FTL; NbExp=3; IntAct=EBI-985879, EBI-713279; CC P37840; P06241: FYN; NbExp=3; IntAct=EBI-985879, EBI-515315; CC P37840; P06241-3: FYN; NbExp=3; IntAct=EBI-985879, EBI-10691738; CC P37840; P62879: GNB2; NbExp=3; IntAct=EBI-985879, EBI-356942; CC P37840; P49841: GSK3B; NbExp=2; IntAct=EBI-985879, EBI-373586; CC P37840; P68431: H3C12; NbExp=3; IntAct=EBI-985879, EBI-79722; CC P37840; Q71DI3: H3C15; NbExp=3; IntAct=EBI-985879, EBI-750650; CC P37840; Q969S8: HDAC10; NbExp=3; IntAct=EBI-985879, EBI-301762; CC P37840; Q9HCC6: HES4; NbExp=3; IntAct=EBI-985879, EBI-2680288; CC P37840; Q8WVV9-3: HNRNPLL; NbExp=3; IntAct=EBI-985879, EBI-25845242; CC P37840; P09017: HOXC4; NbExp=3; IntAct=EBI-985879, EBI-3923226; CC P37840; P08107: HSPA1B; NbExp=7; IntAct=EBI-985879, EBI-629985; CC P37840; P42858: HTT; NbExp=4; IntAct=EBI-985879, EBI-466029; CC P37840; P80217-2: IFI35; NbExp=3; IntAct=EBI-985879, EBI-12823003; CC P37840; Q16352: INA; NbExp=3; IntAct=EBI-985879, EBI-366258; CC P37840; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-985879, EBI-21911304; CC P37840; O14713: ITGB1BP1; NbExp=3; IntAct=EBI-985879, EBI-2127319; CC P37840; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-985879, EBI-2796400; CC P37840; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-985879, EBI-714379; CC P37840; Q92876: KLK6; NbExp=3; IntAct=EBI-985879, EBI-2432309; CC P37840; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-985879, EBI-1044640; CC P37840; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-985879, EBI-11985629; CC P37840; P13473-2: LAMP2; NbExp=3; IntAct=EBI-985879, EBI-21591415; CC P37840; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-985879, EBI-1108377; CC P37840; Q9H2C1: LHX5; NbExp=3; IntAct=EBI-985879, EBI-25835523; CC P37840; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-985879, EBI-10258746; CC P37840; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-985879, EBI-739832; CC P37840; Q8N448: LNX2; NbExp=3; IntAct=EBI-985879, EBI-2340947; CC P37840; A2RU56: LOC401296; NbExp=3; IntAct=EBI-985879, EBI-9088215; CC P37840; Q5S007: LRRK2; NbExp=6; IntAct=EBI-985879, EBI-5323863; CC P37840; O95777: LSM8; NbExp=3; IntAct=EBI-985879, EBI-347779; CC P37840; P07948: LYN; NbExp=3; IntAct=EBI-985879, EBI-79452; CC P37840; Q8TD91-2: MAGEC3; NbExp=3; IntAct=EBI-985879, EBI-10694180; CC P37840; P10636-6: MAPT; NbExp=3; IntAct=EBI-985879, EBI-7796455; CC P37840; P10636-8: MAPT; NbExp=12; IntAct=EBI-985879, EBI-366233; CC P37840; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-985879, EBI-8487781; CC P37840; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-985879, EBI-4397720; CC P37840; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-985879, EBI-21250407; CC P37840; Q8N594: MPND; NbExp=3; IntAct=EBI-985879, EBI-2512452; CC P37840; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-985879, EBI-9092052; CC P37840; P00414: MT-CO3; NbExp=3; IntAct=EBI-985879, EBI-3932264; CC P37840; P02795: MT2A; NbExp=3; IntAct=EBI-985879, EBI-996616; CC P37840; Q9Y483-4: MTF2; NbExp=3; IntAct=EBI-985879, EBI-10698053; CC P37840; O00746: NME4; NbExp=3; IntAct=EBI-985879, EBI-744871; CC P37840; O15381-5: NVL; NbExp=3; IntAct=EBI-985879, EBI-18577082; CC P37840; Q86WS3: OOSP2; NbExp=3; IntAct=EBI-985879, EBI-25888682; CC P37840; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-985879, EBI-1058491; CC P37840; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-985879, EBI-25830200; CC P37840; Q6VY07: PACS1; NbExp=3; IntAct=EBI-985879, EBI-2555014; CC P37840; O96013-2: PAK4; NbExp=3; IntAct=EBI-985879, EBI-21659863; CC P37840; Q9NR21-5: PARP11; NbExp=3; IntAct=EBI-985879, EBI-17159452; CC P37840; Q9NV79: PCMTD2; NbExp=3; IntAct=EBI-985879, EBI-6309018; CC P37840; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-985879, EBI-716063; CC P37840; O75925: PIAS1; NbExp=3; IntAct=EBI-985879, EBI-629434; CC P37840; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-985879, EBI-12891828; CC P37840; P17252: PRKCA; NbExp=3; IntAct=EBI-985879, EBI-1383528; CC P37840; Q02156: PRKCE; NbExp=3; IntAct=EBI-985879, EBI-706254; CC P37840; O60260-5: PRKN; NbExp=8; IntAct=EBI-985879, EBI-21251460; CC P37840; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-985879, EBI-5280197; CC P37840; P62191: PSMC1; NbExp=3; IntAct=EBI-985879, EBI-357598; CC P37840; P17980: PSMC3; NbExp=6; IntAct=EBI-985879, EBI-359720; CC P37840; Q9UI14: RABAC1; NbExp=4; IntAct=EBI-985879, EBI-712367; CC P37840; Q9UJ41-4: RABGEF1; NbExp=3; IntAct=EBI-985879, EBI-14093916; CC P37840; P62826: RAN; NbExp=3; IntAct=EBI-985879, EBI-286642; CC P37840; Q13702-2: RAPSN; NbExp=3; IntAct=EBI-985879, EBI-22012855; CC P37840; P57052: RBM11; NbExp=3; IntAct=EBI-985879, EBI-741332; CC P37840; Q8N5U6: RNF10; NbExp=3; IntAct=EBI-985879, EBI-714023; CC P37840; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-985879, EBI-21535400; CC P37840; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-985879, EBI-25829984; CC P37840; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-985879, EBI-749039; CC P37840; Q8IYW5: RNF168; NbExp=3; IntAct=EBI-985879, EBI-914207; CC P37840; Q96D59: RNF183; NbExp=3; IntAct=EBI-985879, EBI-743938; CC P37840; Q8N488: RYBP; NbExp=3; IntAct=EBI-985879, EBI-752324; CC P37840; O75446: SAP30; NbExp=3; IntAct=EBI-985879, EBI-632609; CC P37840; O00560: SDCBP; NbExp=3; IntAct=EBI-985879, EBI-727004; CC P37840; O43236: SEPTIN4; NbExp=3; IntAct=EBI-985879, EBI-1047513; CC P37840; O75920-2: SERF1B; NbExp=4; IntAct=EBI-985879, EBI-21283682; CC P37840; Q2NKQ1-4: SGSM1; NbExp=3; IntAct=EBI-985879, EBI-10182463; CC P37840; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-985879, EBI-358545; CC P37840; Q01959: SLC6A3; NbExp=3; IntAct=EBI-985879, EBI-6661445; CC P37840; Q9HCE7-2: SMURF1; NbExp=3; IntAct=EBI-985879, EBI-9845742; CC P37840; P37840: SNCA; NbExp=51; IntAct=EBI-985879, EBI-985879; CC P37840; Q9Y6H5: SNCAIP; NbExp=22; IntAct=EBI-985879, EBI-717182; CC P37840; Q9Y6H5-2: SNCAIP; NbExp=2; IntAct=EBI-985879, EBI-15577909; CC P37840; Q16143: SNCB; NbExp=3; IntAct=EBI-985879, EBI-727106; CC P37840; P00441: SOD1; NbExp=9; IntAct=EBI-985879, EBI-990792; CC P37840; P23497-2: SP100; NbExp=3; IntAct=EBI-985879, EBI-6589365; CC P37840; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-985879, EBI-11959123; CC P37840; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-985879, EBI-7067260; CC P37840; Q8TCT7-2: SPPL2B; NbExp=3; IntAct=EBI-985879, EBI-8345366; CC P37840; Q13501: SQSTM1; NbExp=3; IntAct=EBI-985879, EBI-307104; CC P37840; O75886: STAM2; NbExp=3; IntAct=EBI-985879, EBI-373258; CC P37840; Q16623: STX1A; NbExp=2; IntAct=EBI-985879, EBI-712466; CC P37840; Q9BR01-2: SULT4A1; NbExp=3; IntAct=EBI-985879, EBI-25831443; CC P37840; Q92797-2: SYMPK; NbExp=3; IntAct=EBI-985879, EBI-21560407; CC P37840; Q16650: TBR1; NbExp=3; IntAct=EBI-985879, EBI-1047158; CC P37840; Q13569: TDG; NbExp=3; IntAct=EBI-985879, EBI-348333; CC P37840; P28347-2: TEAD1; NbExp=3; IntAct=EBI-985879, EBI-12151837; CC P37840; Q15554-4: TERF2; NbExp=3; IntAct=EBI-985879, EBI-25840535; CC P37840; Q9H0E2: TOLLIP; NbExp=3; IntAct=EBI-985879, EBI-74615; CC P37840; O94811: TPPP; NbExp=8; IntAct=EBI-985879, EBI-3927802; CC P37840; P19474: TRIM21; NbExp=3; IntAct=EBI-985879, EBI-81290; CC P37840; P68363: TUBA1B; NbExp=3; IntAct=EBI-985879, EBI-487083; CC P37840; P07437: TUBB; NbExp=3; IntAct=EBI-985879, EBI-350864; CC P37840; Q8WVJ9: TWIST2; NbExp=3; IntAct=EBI-985879, EBI-1797313; CC P37840; P62987: UBA52; NbExp=3; IntAct=EBI-985879, EBI-357304; CC P37840; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-985879, EBI-749370; CC P37840; O15205: UBD; NbExp=3; IntAct=EBI-985879, EBI-6657186; CC P37840; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-985879, EBI-11530712; CC P37840; Q96RL1-2: UIMC1; NbExp=3; IntAct=EBI-985879, EBI-17761788; CC P37840; O75604-3: USP2; NbExp=3; IntAct=EBI-985879, EBI-10696113; CC P37840; P63027: VAMP2; NbExp=5; IntAct=EBI-985879, EBI-520113; CC P37840; P40337-2: VHL; NbExp=3; IntAct=EBI-985879, EBI-12157263; CC P37840; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-985879, EBI-11141397; CC P37840; O00308: WWP2; NbExp=3; IntAct=EBI-985879, EBI-743923; CC P37840; Q04917: YWHAH; NbExp=4; IntAct=EBI-985879, EBI-306940; CC P37840; O43167-2: ZBTB24; NbExp=3; IntAct=EBI-985879, EBI-25842419; CC P37840; Q96NC0: ZMAT2; NbExp=3; IntAct=EBI-985879, EBI-2682299; CC P37840; Q8WUU4: ZNF296; NbExp=3; IntAct=EBI-985879, EBI-8834821; CC P37840; Q8N895: ZNF366; NbExp=3; IntAct=EBI-985879, EBI-2813661; CC P37840; Q8N988-2: ZNF557; NbExp=3; IntAct=EBI-985879, EBI-10699005; CC P37840; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-985879, EBI-8490788; CC P37840; Q8NBB4-2: ZSCAN1; NbExp=3; IntAct=EBI-985879, EBI-12021938; CC P37840; A8K878; NbExp=3; IntAct=EBI-985879, EBI-25831303; CC P37840; P0DTC9: N; Xeno; NbExp=2; IntAct=EBI-985879, EBI-25475856; CC P37840; Q61327: Slc6a3; Xeno; NbExp=5; IntAct=EBI-985879, EBI-7839708; CC P37840-1; P37840-1: SNCA; NbExp=21; IntAct=EBI-9684465, EBI-9684465; CC P37840-1; Q04917: YWHAH; NbExp=9; IntAct=EBI-9684465, EBI-306940; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19762560, CC ECO:0000269|PubMed:24936070, ECO:0000269|PubMed:25561023, CC ECO:0000269|PubMed:26442590, ECO:0000269|PubMed:31034892, CC ECO:0000269|PubMed:33657088}. Membrane {ECO:0000269|PubMed:24936070}. CC Nucleus {ECO:0000269|PubMed:12859192, ECO:0000269|PubMed:24936070}. CC Synapse {ECO:0000269|PubMed:15282274}. Secreted CC {ECO:0000269|PubMed:24936070}. Cell projection, axon CC {ECO:0000250|UniProtKB:O55042}. Note=Membrane-bound in dopaminergic CC neurons (PubMed:15282274). Expressed and colocalized with SEPTIN4 in CC dopaminergic axon terminals, especially at the varicosities (By CC similarity). {ECO:0000250|UniProtKB:O55042, CC ECO:0000269|PubMed:15282274}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=NACP140; CC IsoId=P37840-1; Sequence=Displayed; CC Name=2-4; Synonyms=NACP112; CC IsoId=P37840-2; Sequence=VSP_006364; CC Name=2-5; CC IsoId=P37840-3; Sequence=VSP_006363; CC -!- TISSUE SPECIFICITY: Highly expressed in presynaptic terminals in the CC central nervous system. Expressed principally in brain. CC {ECO:0000269|PubMed:8194594}. CC -!- DOMAIN: The 'non A-beta component of Alzheimer disease amyloid plaque' CC domain (NAC domain) is involved in fibrils formation. The middle CC hydrophobic region forms the core of the filaments. The C-terminus may CC regulate aggregation and determine the diameter of the filaments. CC {ECO:0000269|PubMed:19722699}. CC -!- PTM: Phosphorylated, predominantly on serine residues. Phosphorylation CC by CK1 appears to occur on residues distinct from the residue CC phosphorylated by other kinases. Phosphorylation of Ser-129 is CC selective and extensive in synucleinopathy lesions. In vitro, CC phosphorylation at Ser-129 promoted insoluble fibril formation. CC Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic CC stress. {ECO:0000269|PubMed:10617630, ECO:0000269|PubMed:10852916, CC ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11813001, CC ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:24936070}. CC -!- PTM: Hallmark lesions of neurodegenerative synucleinopathies contain CC alpha-synuclein that is modified by nitration of tyrosine residues and CC possibly by dityrosine cross-linking to generated stable oligomers. CC -!- PTM: Ubiquitinated. The predominant conjugate is the diubiquitinated CC form. {ECO:0000250|UniProtKB:P37377}. CC -!- PTM: Acetylation at Met-1 seems to be important for proper folding and CC native oligomeric structure. {ECO:0000269|PubMed:22407793}. CC -!- DISEASE: Note=Genetic alterations of SNCA resulting in aberrant CC polymerization into fibrils, are associated with several CC neurodegenerative diseases (synucleinopathies). SNCA fibrillar CC aggregates represent the major non A-beta component of Alzheimer CC disease amyloid plaque, and a major component of Lewy body inclusions. CC They are also found within Lewy body (LB)-like intraneuronal CC inclusions, glial inclusions and axonal spheroids in neurodegeneration CC with brain iron accumulation type 1. CC -!- DISEASE: Parkinson disease 1, autosomal dominant (PARK1) [MIM:168601]: CC A complex neurodegenerative disorder characterized by bradykinesia, CC resting tremor, muscular rigidity and postural instability. Additional CC features are characteristic postural abnormalities, dysautonomia, CC dystonic cramps, and dementia. The pathology of Parkinson disease CC involves the loss of dopaminergic neurons in the substantia nigra and CC the presence of Lewy bodies (intraneuronal accumulations of aggregated CC proteins), in surviving neurons in various areas of the brain. The CC disease is progressive and usually manifests after the age of 50 years, CC although early-onset cases (before 50 years) are known. The majority of CC the cases are sporadic suggesting a multifactorial etiology based on CC environmental and genetic factors. However, some patients present with CC a positive family history for the disease. Familial forms of the CC disease usually begin at earlier ages and are associated with atypical CC clinical features. {ECO:0000269|PubMed:14755719, CC ECO:0000269|PubMed:23427326, ECO:0000269|PubMed:23457019, CC ECO:0000269|PubMed:24936070, ECO:0000269|PubMed:25561023, CC ECO:0000269|PubMed:9197268, ECO:0000269|PubMed:9462735}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Parkinson disease 4, autosomal dominant (PARK4) [MIM:605543]: CC A complex neurodegenerative disorder with manifestations ranging from CC typical Parkinson disease to dementia with Lewy bodies. Clinical CC features include parkinsonian symptoms (resting tremor, rigidity, CC postural instability and bradykinesia), dementia, diffuse Lewy body CC pathology, autonomic dysfunction, hallucinations and paranoia. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Dementia, Lewy body (DLB) [MIM:127750]: A neurodegenerative CC disorder characterized by mental impairment leading to dementia, CC parkinsonism, fluctuating cognitive function, visual hallucinations, CC falls, syncopal episodes, and sensitivity to neuroleptic medication. CC Brainstem or cortical intraneuronal accumulations of aggregated CC proteins (Lewy bodies) are the only essential pathologic features. CC Patients may also have hippocampal and neocortical senile plaques, CC sometimes in sufficient number to fulfill the diagnostic criteria for CC Alzheimer disease. {ECO:0000269|PubMed:14755719}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the synuclein family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L08850; AAA16117.1; -; mRNA. DR EMBL; L36674; AAA98493.1; -; mRNA. DR EMBL; L36675; AAA98487.1; -; mRNA. DR EMBL; D31839; BAA06625.1; -; mRNA. DR EMBL; U46901; AAC02114.1; -; Genomic_DNA. DR EMBL; U46897; AAC02114.1; JOINED; Genomic_DNA. DR EMBL; U46898; AAC02114.1; JOINED; Genomic_DNA. DR EMBL; U46899; AAC02114.1; JOINED; Genomic_DNA. DR EMBL; AF163864; AAG30302.1; -; Genomic_DNA. DR EMBL; AF163864; AAG30303.1; -; Genomic_DNA. DR EMBL; AY049786; AAL15443.1; -; mRNA. DR EMBL; AK290169; BAF82858.1; -; mRNA. DR EMBL; CR457058; CAG33339.1; -; mRNA. DR EMBL; DQ088379; AAY88735.1; -; Genomic_DNA. DR EMBL; CH471057; EAX06036.1; -; Genomic_DNA. DR EMBL; BC013293; AAH13293.1; -; mRNA. DR EMBL; BC108275; AAI08276.1; -; mRNA. DR CCDS; CCDS3634.1; -. [P37840-1] DR CCDS; CCDS43252.1; -. [P37840-2] DR PIR; A49669; A49669. DR PIR; S56746; S56746. DR RefSeq; NP_000336.1; NM_000345.4. [P37840-1] DR RefSeq; NP_001139526.1; NM_001146054.2. [P37840-1] DR RefSeq; NP_001139527.1; NM_001146055.2. [P37840-1] DR RefSeq; NP_001362214.1; NM_001375285.1. [P37840-1] DR RefSeq; NP_001362215.1; NM_001375286.1. [P37840-1] DR RefSeq; NP_001362216.1; NM_001375287.1. [P37840-1] DR RefSeq; NP_001362217.1; NM_001375288.1. [P37840-1] DR RefSeq; NP_009292.1; NM_007308.3. [P37840-2] DR PDB; 10XU; EM; 3.18 A; A/B/C/D/E/U/W/X/Y/Z=35-101. DR PDB; 1XQ8; NMR; -; A=1-140. DR PDB; 2JN5; NMR; -; A=1-12. DR PDB; 2KKW; NMR; -; A=1-140. DR PDB; 2M55; NMR; -; B=1-19. DR PDB; 2N0A; NMR; -; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 2X6M; X-ray; 1.62 A; B=132-140. DR PDB; 3Q25; X-ray; 1.90 A; A=1-19. DR PDB; 3Q26; X-ray; 1.54 A; A=10-42. DR PDB; 3Q27; X-ray; 1.30 A; A=32-57. DR PDB; 3Q28; X-ray; 1.60 A; A=58-79. DR PDB; 3Q29; X-ray; 2.30 A; A/C=1-19. DR PDB; 4BXL; NMR; -; C=35-56. DR PDB; 4R0U; X-ray; 1.38 A; A=72-78. DR PDB; 4R0W; X-ray; 1.50 A; A=70-76. DR PDB; 4RIK; X-ray; 1.85 A; A=69-77. DR PDB; 4RIL; EM; 1.43 A; A=68-78. DR PDB; 4ZNN; EM; 1.41 A; A=47-56. DR PDB; 5CRW; X-ray; 1.60 A; B=31-41. DR PDB; 6A6B; EM; 3.07 A; A/B/C/D/E/F/G/H/I/J/K/L=37-99. DR PDB; 6CT7; X-ray; 1.90 A; S/T=1-10. DR PDB; 6CU7; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6CU8; EM; 3.60 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6H6B; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=1-121. DR PDB; 6I42; X-ray; 1.38 A; B=48-60. DR PDB; 6L1T; EM; 3.22 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6L1U; EM; 3.37 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-140. DR PDB; 6L4S; EM; 3.37 A; A/B/C/D/E/F=45-99. DR PDB; 6LRQ; EM; 3.49 A; A/B/C/D/E/F=1-140. DR PDB; 6OSJ; EM; 2.80 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6OSL; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6OSM; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6PEO; EM; 3.30 A; A/B/C/D/E=1-140. DR PDB; 6PES; EM; 3.60 A; A/B/C/D/E/V/W/X/Y/Z=1-140. DR PDB; 6RT0; EM; 3.10 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6RTB; EM; 3.46 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6SST; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6SSX; EM; 2.98 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6UFR; EM; 2.50 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6XYO; EM; 2.60 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6XYP; EM; 3.29 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 6XYQ; EM; 3.09 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 7C1D; EM; 3.80 A; A/B/C/D/E/F=1-140. DR PDB; 7E0F; EM; 3.02 A; A/B/C/D/E/F=1-140. DR PDB; 7L7H; EM; 4.00 A; A/B/C/D/E/F/G/H=1-140. DR PDB; 7LC9; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=41-140. DR PDB; 7NCA; EM; 3.47 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 7NCG; EM; 3.43 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 7NCH; EM; 3.84 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 7NCI; EM; 3.55 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 7NCJ; EM; 4.23 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 7NCK; EM; 3.18 A; A/B/C/D/E/F=1-140. DR PDB; 7OZG; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 7OZH; EM; 3.02 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 7STX; EM; 3.14 A; C=1-5. DR PDB; 7UAK; EM; 3.38 A; A/B/C/D/E/F=1-140. DR PDB; 7V47; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 7V48; EM; 3.00 A; A/B/C/D/E/F=1-140. DR PDB; 7V49; EM; 3.40 A; A/B/C=1-140. DR PDB; 7V4A; EM; 3.20 A; A/B/C=1-140. DR PDB; 7V4B; EM; 3.10 A; A/B/C/D/E/F=1-140. DR PDB; 7V4C; EM; 3.30 A; A/B/F=1-140. DR PDB; 7V4D; EM; 3.50 A; A/B/C/D/E/F=1-140. DR PDB; 7WMM; EM; 2.60 A; A/B/C/D/E/F=1-140. DR PDB; 7WNZ; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=36-100. DR PDB; 7WO0; EM; 2.70 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=35-99. DR PDB; 7XJX; EM; 2.70 A; A/B/C/D/E/F=1-140. DR PDB; 7XO0; EM; 3.00 A; A/B/C/D/E/F=1-140. DR PDB; 7XO1; EM; 3.00 A; A/B/C/D/E/F=1-140. DR PDB; 7XO2; EM; 3.00 A; A/B/C/D/E/I=1-140. DR PDB; 7XO3; EM; 2.60 A; A/B/C/D/E/F=1-140. DR PDB; 7YK2; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 7YK8; EM; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 7YNF; EM; 2.50 A; A/B/C/D/E/F=1-140. DR PDB; 7YNG; EM; 3.10 A; A/B/C/D/E/F=1-140. DR PDB; 7YNL; EM; 2.60 A; A/B/C/D/E/F/G/H=1-140. DR PDB; 7YNM; EM; 2.90 A; A/B/C/D/G/H/I/J=1-140. DR PDB; 7YNN; EM; 2.90 A; A/B/C/D/G/H/I/J=1-140. DR PDB; 7YNO; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 7YNP; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 7YNQ; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 7YNR; EM; 2.90 A; A/B/C/D/E/F=1-140. DR PDB; 7YNS; EM; 3.00 A; A/B/C/D/E/F=1-140. DR PDB; 7YNT; EM; 3.10 A; A/B/C/D/E/F=1-140. DR PDB; 8A4L; EM; 2.68 A; A/B/C/D/E/F/G/H/I/J/K/L/M/O/P=1-140. DR PDB; 8A9L; EM; 2.16 A; A=1-140. DR PDB; 8ADS; EM; 3.05 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8ADU; EM; 3.24 A; A/B/C/D/E=1-140. DR PDB; 8ADV; EM; 2.98 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8ADW; EM; 2.95 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8AEX; EM; 2.76 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8B9V; X-ray; 2.16 A; A=110-119. DR PDB; 8BQV; EM; 2.00 A; A=1-140. DR PDB; 8BQW; EM; 2.30 A; A/C=1-140. DR PDB; 8CE7; EM; 2.70 A; A/C=1-140. DR PDB; 8CEB; EM; 2.70 A; A/C=1-140. DR PDB; 8CYR; EM; 4.20 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CYS; EM; 3.10 A; A/B/C/D/E/F/G/I/J/K/L/M/N/O=1-140. DR PDB; 8CYT; EM; 3.00 A; A/B/C/D/E/F/G/I/J/K/L/M/N/O=1-140. DR PDB; 8CYV; EM; 3.50 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CYW; EM; 3.10 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CYX; EM; 3.00 A; A/B/C/D/E/I/J/K/L/M=1-140. DR PDB; 8CYY; EM; 3.10 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CZ0; EM; 2.90 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CZ1; EM; 3.00 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CZ2; EM; 3.00 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CZ3; EM; 3.20 A; A/B/C/D/E/F/I/J/K/L/M/N=1-140. DR PDB; 8CZ6; EM; 3.20 A; A/B/C/D/E/F/G/I/J/K/L/M/N/O=1-140. DR PDB; 8FPT; NMR; -; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8G0L; EM; 3.39 A; C=1-5. DR PDB; 8GF7; EM; 4.80 A; A/B/C/D/E/F=7-96. DR PDB; 8H03; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 8H04; EM; 3.00 A; A/B/C/D/E/F=1-140. DR PDB; 8H05; EM; 3.40 A; A/B/C=1-140. DR PDB; 8HZB; EM; 3.20 A; A/B/C/D/E/F=1-140. DR PDB; 8HZC; EM; 3.20 A; A/B/C/D/E/F=1-140. DR PDB; 8HZS; EM; 3.30 A; A/B/C/D/E/F=1-140. DR PDB; 8JEX; EM; 3.10 A; A/B/G/H/K/P=1-140. DR PDB; 8JEY; EM; 2.60 A; A/B/C/D/E/F=1-140. DR PDB; 8JJV; X-ray; 1.23 A; B=43-56. DR PDB; 8JLY; X-ray; 1.29 A; B=43-56. DR PDB; 8OG0; X-ray; 1.71 A; P=136-140. DR PDB; 8OJR; NMR; -; A=1-25. DR PDB; 8OL8; NMR; -; A=2-12. DR PDB; 8OQI; EM; 3.10 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8PIX; EM; 3.41 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8PJO; EM; 2.31 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8PK2; EM; 3.26 A; A/B/C/D/E=1-140. DR PDB; 8PK4; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8QPZ; EM; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L=8-140. DR PDB; 8RI9; EM; 3.30 A; A/B/C/D/E=1-140. DR PDB; 8RQM; EM; 3.20 A; A/B/C/D/E/F=1-140. DR PDB; 8RRR; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7B; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7L; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7M; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7O; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7P; EM; 2.70 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7Q; EM; 2.70 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8X7R; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 8XWD; EM; 3.10 A; A/B/C/D/E/F=1-140. DR PDB; 8Y2P; EM; 3.20 A; A/B/C/D/E/F=1-140. DR PDB; 8Y2Q; EM; 2.80 A; A/B/C/D/E/F=1-140. DR PDB; 8ZLI; EM; 3.40 A; A/B/C/D/E/F/I/J/K/L=45-99. DR PDB; 8ZLO; EM; 3.10 A; A/B/C/D/E/F/G/H/I/J/O/T=45-99. DR PDB; 8ZLP; EM; 3.50 A; A/B/C/F/G/H=1-98. DR PDB; 8ZMY; EM; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=1-98. DR PDB; 8ZVY; X-ray; 1.72 A; C/D=121-140. DR PDB; 8ZWH; EM; 2.50 A; A/B/C/D/E/F=1-140. DR PDB; 8ZWI; EM; 3.00 A; A/B/C/D/E/F=1-140. DR PDB; 8ZWJ; EM; 3.10 A; A/B/C/D/E/G=1-140. DR PDB; 8ZWK; EM; 3.40 A; A/B/C/D/E/F=1-140. DR PDB; 9C5R; EM; 2.61 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9CD9; EM; 3.20 A; E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z=1-140. DR PDB; 9CDA; EM; 3.30 A; K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b=1-140. DR PDB; 9CK3; EM; 2.04 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9CKK; EM; 2.21 A; A/B/C/D/E/F/G/H=1-140. DR PDB; 9CKL; EM; 2.68 A; A/B/C/D/E/F/G/H=1-140. DR PDB; 9CX6; EM; 3.20 A; G/H=1-140. DR PDB; 9D5C; EM; 4.80 A; A/B/C/F/G/H=1-96. DR PDB; 9E8U; EM; 2.60 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9E8V; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9E8W; EM; 2.80 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9E8X; EM; 2.80 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9E8Y; EM; 2.90 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9E9X; EM; 3.20 A; A/B/C/D/E/F=1-140. DR PDB; 9EUU; EM; 1.93 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=1-140. DR PDB; 9FYP; EM; 2.23 A; I/J/K/L/M/N/O/P/Q/R=1-140. DR PDB; 9HC6; EM; 2.79 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-140. DR PDB; 9HC7; EM; 2.85 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-140. DR PDB; 9HC8; EM; 2.82 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9HC9; EM; 2.76 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-140. DR PDB; 9HCA; EM; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-140. DR PDB; 9HCB; EM; 2.95 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9HGR; EM; 2.70 A; A/B=1-140. DR PDB; 9HGS; EM; 3.00 A; C=1-140. DR PDB; 9HXA; EM; 3.70 A; A/C=1-140. DR PDB; 9IC7; EM; 2.90 A; a/b/c/d/e/f/g/h/i/j/k/l/m/n=1-140. DR PDB; 9IJP; EM; 3.10 A; B/C/E/G/I/L=1-140. DR PDB; 9JBY; EM; 3.49 A; A/B/C/D/E/F=37-98. DR PDB; 9JC3; EM; 2.39 A; D/E/F/G/H/I=1-140. DR PDB; 9JC4; EM; 2.95 A; B/C/D/F/G/H=1-140. DR PDB; 9JC5; EM; 3.23 A; A/B/C/D/E/F=1-140. DR PDB; 9JD7; EM; 3.57 A; A/B/C/D/E/F=1-140. DR PDB; 9JD8; EM; 3.86 A; A/B/C/D/E/F/G/H/I=1-140. DR PDB; 9JDK; EM; 3.32 A; A/B/C/D/E/F=37-99. DR PDB; 9JE2; EM; 3.06 A; C/D/E/F/G/H=1-140. DR PDB; 9JE4; EM; 3.37 A; A/B/C=1-140. DR PDB; 9JE6; EM; 3.43 A; A/B/C/D/E/F=1-140. DR PDB; 9JE7; EM; 3.36 A; A/C/E=1-140. DR PDB; 9JE8; EM; 3.60 A; B/C/D/E/F/G=1-140. DR PDB; 9JI8; EM; 2.85 A; F/G/K/L/M/O=37-99. DR PDB; 9JKE; EM; 3.40 A; A/B/C/D/E/F=37-98. DR PDB; 9JO6; NMR; -; A=1-140. DR PDB; 9K7Q; X-ray; 4.58 A; M=1-92. DR PDB; 9KA3; EM; 2.72 A; A/B/C/D/E/F=1-140. DR PDB; 9KA4; EM; 3.42 A; A/B/C/D/E/F=1-140. DR PDB; 9KAL; EM; 3.36 A; A/B/C=1-140. DR PDB; 9KC2; EM; 2.90 A; C/D/E/F/G/H=1-140. DR PDB; 9KCN; EM; 2.60 A; L/M/N/P/Q/R/d/e/f/h/i/j=37-140. DR PDB; 9KCO; EM; 3.10 A; F/G/H/I/J/K/L/M/N/O/P/Q=1-140. DR PDB; 9KCP; EM; 2.70 A; D/E/F/G/H/I=1-140. DR PDB; 9M5K; EM; 3.10 A; A/B/C=1-140. DR PDB; 9M5L; EM; 3.27 A; A/B/C=1-140. DR PDB; 9O4B; EM; 2.59 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9O9J; EM; 2.30 A; A/D=1-140. DR PDB; 9O9K; EM; 2.90 A; A=1-140. DR PDB; 9OBP; EM; 2.50 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9QYL; EM; 3.08 A; E/F/G/H/J/K/L/M/N/O/P/Q/e/f/g/h/j/k/l/m/n/o/p/q=1-140. DR PDB; 9QYN; EM; 3.13 A; G/H/I/J/K/L/M/N/O/P=1-140. DR PDB; 9RB3; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9RB6; EM; 3.02 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9RB7; EM; 3.45 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9RB8; EM; 3.64 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9RB9; EM; 3.04 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9RBA; EM; 3.54 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9RBB; EM; 3.15 A; A/B/C/D/E/F/G/H/I/J=1-140. DR PDB; 9TPT; EM; 3.43 A; A/B/C/D/E/F/H/I/J/L/M/N=36-100. DR PDB; 9UF6; EM; 2.90 A; E/F/G/H/I/J/K/L/M/N/O/P=1-140. DR PDB; 9UFD; EM; 2.70 A; E/F/G/H/I/J/K/L/M/N/O/P=1-140. DR PDB; 9UFF; EM; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9UFL; EM; 2.60 A; A/B/C/D/E/F=1-140. DR PDB; 9UFS; EM; 2.70 A; A/B/C/D/E/F=1-140. DR PDB; 9UFX; EM; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9UFY; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9UG0; EM; 3.10 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9UG1; EM; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L=1-140. DR PDB; 9UJQ; EM; 2.90 A; E/F/G/H/I/J=1-140. DR PDB; 9V6U; EM; 3.30 A; c/d/e/f/g/h/i/j/k/o/p/q/r/s/t=1-140. DR PDB; 9V7C; EM; 3.30 A; c/d/e/f/g/h/i/j/k/o/p/q/r/s/t=32-101. DR PDB; 9Y0S; EM; 2.72 A; A/B/C/D/E/F/G/H/I/J=1-140. DR AlphaFoldDB; P37840; -. DR BMRB; P37840; -. DR EMDB; EMD-0148; -. DR EMDB; EMD-0801; -. DR EMDB; EMD-0803; -. DR EMDB; EMD-0833; -. DR EMDB; EMD-0958; -. DR EMDB; EMD-10305; -. DR EMDB; EMD-10307; -. DR EMDB; EMD-10650; -. DR EMDB; EMD-10651; -. DR EMDB; EMD-10652; -. DR EMDB; EMD-12264; -. DR EMDB; EMD-12265; -. DR EMDB; EMD-12266; -. DR EMDB; EMD-12267; -. DR EMDB; EMD-12268; -. DR EMDB; EMD-12269; -. DR EMDB; EMD-13123; -. DR EMDB; EMD-13124; -. DR EMDB; EMD-15148; -. DR EMDB; EMD-15285; -. DR EMDB; EMD-15369; -. DR EMDB; EMD-15370; -. DR EMDB; EMD-15371; -. DR EMDB; EMD-15372; -. DR EMDB; EMD-15388; -. DR EMDB; EMD-16188; -. DR EMDB; EMD-16189; -. DR EMDB; EMD-16600; -. DR EMDB; EMD-16603; -. DR EMDB; EMD-17111; -. DR EMDB; EMD-17693; -. DR EMDB; EMD-17714; -. DR EMDB; EMD-17723; -. DR EMDB; EMD-17726; -. DR EMDB; EMD-18570; -. DR EMDB; EMD-19184; -. DR EMDB; EMD-19446; -. DR EMDB; EMD-19462; -. DR EMDB; EMD-19986; -. DR EMDB; EMD-20183; -. DR EMDB; EMD-20185; -. DR EMDB; EMD-20186; -. DR EMDB; EMD-20328; -. DR EMDB; EMD-20331; -. DR EMDB; EMD-20759; -. DR EMDB; EMD-23212; -. DR EMDB; EMD-23270; -. DR EMDB; EMD-25438; -. DR EMDB; EMD-26427; -. DR EMDB; EMD-27082; -. DR EMDB; EMD-27083; -. DR EMDB; EMD-27084; -. DR EMDB; EMD-27085; -. DR EMDB; EMD-27086; -. DR EMDB; EMD-27087; -. DR EMDB; EMD-27088; -. DR EMDB; EMD-27089; -. DR EMDB; EMD-27090; -. DR EMDB; EMD-27091; -. DR EMDB; EMD-27092; -. DR EMDB; EMD-27093; -. DR EMDB; EMD-29657; -. DR EMDB; EMD-29980; -. DR EMDB; EMD-30269; -. DR EMDB; EMD-30931; -. DR EMDB; EMD-3094; -. DR EMDB; EMD-3095; -. DR EMDB; EMD-31702; -. DR EMDB; EMD-31703; -. DR EMDB; EMD-31704; -. DR EMDB; EMD-31705; -. DR EMDB; EMD-31706; -. DR EMDB; EMD-31707; -. DR EMDB; EMD-31708; -. DR EMDB; EMD-32615; -. DR EMDB; EMD-32636; -. DR EMDB; EMD-32637; -. DR EMDB; EMD-33236; -. DR EMDB; EMD-33332; -. DR EMDB; EMD-33333; -. DR EMDB; EMD-33334; -. DR EMDB; EMD-33335; -. DR EMDB; EMD-33884; -. DR EMDB; EMD-33890; -. DR EMDB; EMD-33960; -. DR EMDB; EMD-33961; -. DR EMDB; EMD-33965; -. DR EMDB; EMD-33966; -. DR EMDB; EMD-33967; -. DR EMDB; EMD-33968; -. DR EMDB; EMD-33969; -. DR EMDB; EMD-33970; -. DR EMDB; EMD-33971; -. DR EMDB; EMD-35087; -. DR EMDB; EMD-35088; -. DR EMDB; EMD-35090; -. DR EMDB; EMD-36202; -. DR EMDB; EMD-36203; -. DR EMDB; EMD-38097; -. DR EMDB; EMD-38103; -. DR EMDB; EMD-38104; -. DR EMDB; EMD-38105; -. DR EMDB; EMD-38106; -. DR EMDB; EMD-38107; -. DR EMDB; EMD-38108; -. DR EMDB; EMD-38733; -. DR EMDB; EMD-38862; -. DR EMDB; EMD-38863; -. DR EMDB; EMD-45221; -. DR EMDB; EMD-45464; -. DR EMDB; EMD-45465; -. DR EMDB; EMD-45639; -. DR EMDB; EMD-45650; -. DR EMDB; EMD-45651; -. DR EMDB; EMD-45979; -. DR EMDB; EMD-47731; -. DR EMDB; EMD-47732; -. DR EMDB; EMD-47733; -. DR EMDB; EMD-47734; -. DR EMDB; EMD-47735; -. DR EMDB; EMD-47820; -. DR EMDB; EMD-4994; -. DR EMDB; EMD-4996; -. DR EMDB; EMD-50077; -. DR EMDB; EMD-50860; -. DR EMDB; EMD-50888; -. DR EMDB; EMD-52038; -. DR EMDB; EMD-52039; -. DR EMDB; EMD-52040; -. DR EMDB; EMD-52041; -. DR EMDB; EMD-52042; -. DR EMDB; EMD-52043; -. DR EMDB; EMD-52165; -. DR EMDB; EMD-52166; -. DR EMDB; EMD-52458; -. DR EMDB; EMD-52833; -. DR EMDB; EMD-53453; -. DR EMDB; EMD-53456; -. DR EMDB; EMD-53884; -. DR EMDB; EMD-53885; -. DR EMDB; EMD-53886; -. DR EMDB; EMD-53887; -. DR EMDB; EMD-53888; -. DR EMDB; EMD-53889; -. DR EMDB; EMD-53890; -. DR EMDB; EMD-54402; -. DR EMDB; EMD-56114; -. DR EMDB; EMD-60226; -. DR EMDB; EMD-60231; -. DR EMDB; EMD-60232; -. DR EMDB; EMD-60262; -. DR EMDB; EMD-60527; -. DR EMDB; EMD-60528; -. DR EMDB; EMD-60529; -. DR EMDB; EMD-60530; -. DR EMDB; EMD-60637; -. DR EMDB; EMD-61330; -. DR EMDB; EMD-61355; -. DR EMDB; EMD-61356; -. DR EMDB; EMD-61357; -. DR EMDB; EMD-61383; -. DR EMDB; EMD-61384; -. DR EMDB; EMD-61394; -. DR EMDB; EMD-61405; -. DR EMDB; EMD-61406; -. DR EMDB; EMD-61408; -. DR EMDB; EMD-61409; -. DR EMDB; EMD-61410; -. DR EMDB; EMD-61500; -. DR EMDB; EMD-61552; -. DR EMDB; EMD-62203; -. DR EMDB; EMD-62204; -. DR EMDB; EMD-62212; -. DR EMDB; EMD-62239; -. DR EMDB; EMD-62257; -. DR EMDB; EMD-62258; -. DR EMDB; EMD-62259; -. DR EMDB; EMD-63644; -. DR EMDB; EMD-63645; -. DR EMDB; EMD-64102; -. DR EMDB; EMD-64105; -. DR EMDB; EMD-64107; -. DR EMDB; EMD-64111; -. DR EMDB; EMD-64121; -. DR EMDB; EMD-64125; -. DR EMDB; EMD-64126; -. DR EMDB; EMD-64128; -. DR EMDB; EMD-64129; -. DR EMDB; EMD-64224; -. DR EMDB; EMD-64808; -. DR EMDB; EMD-64811; -. DR EMDB; EMD-6482; -. DR EMDB; EMD-6988; -. DR EMDB; EMD-70093; -. DR EMDB; EMD-70252; -. DR EMDB; EMD-70253; -. DR EMDB; EMD-70295; -. DR EMDB; EMD-72396; -. DR EMDB; EMD-75514; -. DR EMDB; EMD-7618; -. DR EMDB; EMD-7619; -. DR SMR; P37840; -. DR BioGRID; 112506; 1684. DR CORUM; P37840; -. DR DIP; DIP-35354N; -. DR FunCoup; P37840; 336. DR IntAct; P37840; 474. DR NDEx; IQUERY-CP-SNCA; 11 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000500990; -. DR BindingDB; P37840; -. DR ChEMBL; CHEMBL6152; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB04209; Dequalinium. DR DrugBank; DB13927; Emrusolmin. DR DrugBank; DB02709; Resveratrol. DR DrugCentral; P37840; -. DR GuidetoPHARMACOLOGY; 3285; -. DR TCDB; 1.C.77.1.1; the synuclein (synuclein) family. DR GlyConnect; P37840; 1 O-GlcNAc glycan (1 site). DR GlyCosmos; P37840; 6 sites, 2 glycans. DR GlyGen; P37840; 7 sites, 2 O-linked glycans (7 sites). DR iPTMnet; P37840; -. DR MetOSite; P37840; -. DR PhosphoSitePlus; P37840; -. DR SwissPalm; P37840; -. DR BioMuta; SNCA; -. DR DMDM; 586067; -. DR jPOST; P37840; -. DR MassIVE; P37840; -. DR PaxDb; 9606-ENSP00000500990; -. DR PeptideAtlas; P37840; -. DR ProteomicsDB; 55279; -. [P37840-1] DR ProteomicsDB; 55280; -. [P37840-2] DR ProteomicsDB; 55281; -. [P37840-3] DR Pumba; P37840; -. DR TopDownProteomics; P37840-1; -. [P37840-1] DR ABCD; P37840; 25 sequenced antibodies. DR Antibodypedia; 14688; 3416 antibodies from 60 providers. DR DNASU; 6622; -. DR Ensembl; ENST00000336904.7; ENSP00000338345.3; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000345009.8; ENSP00000343683.4; ENSG00000145335.18. [P37840-2] DR Ensembl; ENST00000394986.5; ENSP00000378437.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000394989.6; ENSP00000378440.2; ENSG00000145335.18. [P37840-3] DR Ensembl; ENST00000394991.8; ENSP00000378442.4; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000420646.6; ENSP00000396241.2; ENSG00000145335.18. [P37840-2] DR Ensembl; ENST00000505199.5; ENSP00000421485.1; ENSG00000145335.18. [P37840-3] DR Ensembl; ENST00000506244.5; ENSP00000422238.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000508895.5; ENSP00000426955.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000618500.4; ENSP00000484044.1; ENSG00000145335.18. [P37840-3] DR Ensembl; ENST00000673718.1; ENSP00000500990.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000889657.1; ENSP00000559716.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000889658.1; ENSP00000559717.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000889659.1; ENSP00000559718.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000889660.1; ENSP00000559719.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000889662.1; ENSP00000559720.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000889663.1; ENSP00000559722.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000912364.1; ENSP00000582423.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000912365.1; ENSP00000582424.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965186.1; ENSP00000635245.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965187.1; ENSP00000635246.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965188.1; ENSP00000635247.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965189.1; ENSP00000635248.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965190.1; ENSP00000635249.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965191.1; ENSP00000635250.1; ENSG00000145335.18. [P37840-1] DR Ensembl; ENST00000965192.1; ENSP00000635251.1; ENSG00000145335.18. [P37840-1] DR GeneID; 6622; -. DR KEGG; hsa:6622; -. DR MANE-Select; ENST00000394991.8; ENSP00000378442.4; NM_000345.4; NP_000336.1. DR UCSC; uc003hso.3; human. [P37840-1] DR AGR; HGNC:11138; -. DR ClinPGx; PA35986; -. DR CTD; 6622; -. DR DisGeNET; 6622; -. DR GeneCards; SNCA; -. DR GeneReviews; SNCA; -. DR HGNC; HGNC:11138; SNCA. DR HPA; ENSG00000145335; Group enriched (bone marrow, brain). DR MalaCards; SNCA; -. DR MIM; 127750; phenotype. DR MIM; 163890; gene. DR MIM; 168600; phenotype. DR MIM; 168601; phenotype. DR MIM; 605543; phenotype. DR OpenTargets; ENSG00000145335; -. DR Orphanet; 411602; Hereditary late-onset Parkinson disease. DR Orphanet; 171695; Parkinsonian-pyramidal syndrome. DR Orphanet; 2828; Young-onset Parkinson disease. DR VEuPathDB; HostDB:ENSG00000145335; -. DR eggNOG; ENOG502S0Q7; Eukaryota. DR GeneTree; ENSGT00950000183175; -. DR HOGENOM; CLU_129378_1_0_1; -. DR InParanoid; P37840; -. DR OMA; AAGXTKE; -. DR OrthoDB; 9900372at2759; -. DR PAN-GO; P37840; 10 GO annotations based on evolutionary models. DR PhylomeDB; P37840; -. DR PathwayCommons; P37840; -. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; P37840; -. DR SIGNOR; P37840; -. DR Agora; ENSG00000145335; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 6622; 12 hits in 1150 CRISPR screens. DR CD-CODE; 232F8A39; P-body. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; SNCA; human. DR EvolutionaryTrace; P37840; -. DR GeneWiki; Alpha-synuclein; -. DR GenomeRNAi; 6622; -. DR Pharos; P37840; Tchem. DR PRO; PR:P37840; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P37840; protein. DR Bgee; ENSG00000145335; Expressed in trabecular bone tissue and 205 other cell types or tissues. DR ExpressionAtlas; P37840; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:0043679; C:axon terminus; IBA:GO_Central. DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IDA:UniProtKB. DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB. DR GO; GO:0097413; C:Lewy body; IDA:MGI. DR GO; GO:0005764; C:lysosome; TAS:ParkinsonsUK-UCL. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl. DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; TAS:ParkinsonsUK-UCL. DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central. DR GO; GO:0005640; C:nuclear outer membrane; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB. DR GO; GO:0005840; C:ribosome; IEA:Ensembl. DR GO; GO:0099512; C:supramolecular fiber; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; EXP:UniProtKB. DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central. DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl. DR GO; GO:0003779; F:actin binding; IPI:ARUK-UCL. DR GO; GO:0043014; F:alpha-tubulin binding; IPI:UniProtKB. DR GO; GO:0048487; F:beta-tubulin binding; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:1903136; F:cuprous ion binding; IMP:CAFA. DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB. DR GO; GO:0070840; F:dynein complex binding; IPI:UniProtKB. DR GO; GO:0008047; F:enzyme activator activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:BHF-UCL. DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0030544; F:Hsp70 protein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0019894; F:kinesin binding; IPI:UniProtKB. DR GO; GO:0008289; F:lipid binding; EXP:DisProt. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl. DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB. DR GO; GO:0043274; F:phospholipase binding; IEA:Ensembl. DR GO; GO:0005543; F:phospholipid binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0051219; F:phosphoprotein binding; IDA:BHF-UCL. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ARUK-UCL. DR GO; GO:0140311; F:protein sequestering activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0000149; F:SNARE binding; IDA:UniProtKB. DR GO; GO:0048156; F:tau protein binding; IDA:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0141108; F:transporter regulator activity; IGI:ARUK-UCL. DR GO; GO:0015631; F:tubulin binding; EXP:DisProt. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:1990000; P:amyloid fibril formation; EXP:DisProt. DR GO; GO:0048148; P:behavioral response to cocaine; IEA:Ensembl. DR GO; GO:0071280; P:cellular response to copper ion; IDA:UniProtKB. DR GO; GO:0071872; P:cellular response to epinephrine stimulus; TAS:UniProtKB. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:ParkinsonsUK-UCL. DR GO; GO:0042416; P:dopamine biosynthetic process; TAS:UniProtKB. DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; TAS:UniProtKB. DR GO; GO:0006749; P:glutathione metabolic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0001774; P:microglial cell activation; TAS:ParkinsonsUK-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:1904715; P:negative regulation of chaperone-mediated autophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0045963; P:negative regulation of dopamine metabolic process; IEA:Ensembl. DR GO; GO:0051585; P:negative regulation of dopamine uptake involved in synaptic transmission; IDA:UniProtKB. DR GO; GO:0045920; P:negative regulation of exocytosis; IMP:UniProtKB. DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IDA:BHF-UCL. DR GO; GO:1902957; P:negative regulation of mitochondrial electron transport, NADH to ubiquinone; TAS:ParkinsonsUK-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0051622; P:negative regulation of norepinephrine uptake; IDA:UniProtKB. DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0051612; P:negative regulation of serotonin uptake; IDA:UniProtKB. DR GO; GO:0070495; P:negative regulation of thrombin-activated receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:ParkinsonsUK-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:ParkinsonsUK-UCL. DR GO; GO:0045807; P:positive regulation of endocytosis; IDA:UniProtKB. DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:UniProtKB. DR GO; GO:1903285; P:positive regulation of hydrogen peroxide catabolic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:ParkinsonsUK-UCL. DR GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:1904377; P:positive regulation of protein localization to cell periphery; IGI:ParkinsonsUK-UCL. DR GO; GO:0001921; P:positive regulation of receptor recycling; IDA:UniProtKB. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IDA:UniProtKB. DR GO; GO:0035543; P:positive regulation of SNARE complex assembly; IDA:CACAO. DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB. DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB. DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB. DR GO; GO:0014059; P:regulation of dopamine secretion; TAS:UniProtKB. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:BHF-UCL. DR GO; GO:0051621; P:regulation of norepinephrine uptake; IGI:ARUK-UCL. DR GO; GO:1905606; P:regulation of presynapse assembly; IGI:ARUK-UCL. DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; TAS:ParkinsonsUK-UCL. DR GO; GO:1903421; P:regulation of synaptic vesicle recycling; TAS:ParkinsonsUK-UCL. DR GO; GO:1904307; P:response to desipramine; IEA:Ensembl. DR GO; GO:0070555; P:response to interleukin-1; IDA:UniProtKB. DR GO; GO:0010040; P:response to iron(II) ion; IDA:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0032026; P:response to magnesium ion; IDA:UniProtKB. DR GO; GO:0034341; P:response to type II interferon; IDA:UniProtKB. DR GO; GO:0035493; P:SNARE complex assembly; IDA:UniProtKB. DR GO; GO:0097435; P:supramolecular fiber organization; TAS:UniProtKB. DR GO; GO:0050808; P:synapse organization; IBA:GO_Central. DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IBA:GO_Central. DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB. DR GO; GO:0016079; P:synaptic vesicle exocytosis; IDA:UniProtKB. DR GO; GO:0016082; P:synaptic vesicle priming; IMP:UniProtKB. DR GO; GO:0048489; P:synaptic vesicle transport; IBA:GO_Central. DR DisProt; DP00070; -. DR FunFam; 1.10.287.700:FF:000001; Alpha-synuclein; 1. DR Gene3D; 1.10.287.700; Helix hairpin bin; 1. DR IDEAL; IID00302; -. DR InterPro; IPR001058; Synuclein. DR InterPro; IPR002460; Synuclein_alpha. DR PANTHER; PTHR13820:SF5; ALPHA-SYNUCLEIN; 1. DR PANTHER; PTHR13820; SYNUCLEIN; 1. DR Pfam; PF01387; Synuclein; 1. DR PRINTS; PR01212; ASYNUCLEIN. DR PRINTS; PR01211; SYNUCLEIN. DR SUPFAM; SSF118375; Synuclein; 1. DR PCDDB; P37840; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Alzheimer disease; KW Amyloid; Cell projection; Copper; Cytoplasm; Direct protein sequencing; KW Disease variant; Membrane; Metal-binding; Neurodegeneration; Nucleus; KW Parkinson disease; Parkinsonism; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Secreted; Synapse; Ubl conjugation. FT CHAIN 1..140 FT /note="Alpha-synuclein" FT /id="PRO_0000184022" FT REPEAT 20..30 FT /note="1" FT REPEAT 31..41 FT /note="2" FT REPEAT 42..56 FT /note="3; approximate" FT REPEAT 57..67 FT /note="4" FT REGION 20..67 FT /note="4 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V- FT X(4)" FT REGION 100..140 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 111..140 FT /note="Interaction with SERF1A" FT /evidence="ECO:0000269|PubMed:22854022" FT COMPBIAS 112..140 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 2 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /evidence="ECO:0000305" FT BINDING 50 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /evidence="ECO:0000305" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:22407793" FT MOD_RES 87 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10617630" FT MOD_RES 125 FT /note="Phosphotyrosine; by FYN" FT /evidence="ECO:0000269|PubMed:11162638, FT ECO:0000269|PubMed:12893833" FT MOD_RES 129 FT /note="Phosphoserine; by GRK2, PLK2, CK2, CK1 and GRK5" FT /evidence="ECO:0000269|PubMed:10617630, FT ECO:0000269|PubMed:11813001, ECO:0000269|PubMed:24936070" FT VAR_SEQ 41..54 FT /note="Missing (in isoform 2-5)" FT /evidence="ECO:0000303|PubMed:7601450" FT /id="VSP_006363" FT VAR_SEQ 103..130 FT /note="Missing (in isoform 2-4)" FT /evidence="ECO:0000303|PubMed:7601450, FT ECO:0000303|PubMed:7802671" FT /id="VSP_006364" FT VARIANT 30 FT /note="A -> P (in PARK1; no effect on oligomerization; FT dbSNP:rs104893878)" FT /evidence="ECO:0000269|PubMed:25561023, FT ECO:0000269|PubMed:9462735" FT /id="VAR_007957" FT VARIANT 46 FT /note="E -> K (in PARK1 and DLB; significant increase in FT binding to negatively charged phospholipid liposomes; FT increases oligomerization; dbSNP:rs104893875)" FT /evidence="ECO:0000269|PubMed:14755719, FT ECO:0000269|PubMed:15498564, ECO:0000269|PubMed:25561023" FT /id="VAR_022703" FT VARIANT 50 FT /note="H -> Q (in PARK1; no effect on protein structure; no FT effect on phosphorylation of the protein; no effect on FT membrane- and lipid-binding; increases oligomerization; FT increases fibril formation; increases secretion of the FT protein; impairs copper-binding; dbSNP:rs201106962)" FT /evidence="ECO:0000269|PubMed:23427326, FT ECO:0000269|PubMed:23457019, ECO:0000269|PubMed:24936070, FT ECO:0000269|PubMed:25561023" FT /id="VAR_070171" FT VARIANT 53 FT /note="A -> T (in PARK1; no effect on osmotic FT stress-induced phosphorylation; increases oligomerization; FT dbSNP:rs104893877)" FT /evidence="ECO:0000269|PubMed:12893833, FT ECO:0000269|PubMed:25561023, ECO:0000269|PubMed:9197268" FT /id="VAR_007454" FT MUTAGEN 2 FT /note="D->A: Impairs copper-binding." FT /evidence="ECO:0000269|PubMed:21319811" FT MUTAGEN 35 FT /note="E->K: No effect on oligomerization." FT /evidence="ECO:0000269|PubMed:25561023" FT MUTAGEN 39 FT /note="Y->F: No effect on osmotic stress-induced FT phosphorylation." FT /evidence="ECO:0000269|PubMed:12893833" FT MUTAGEN 50 FT /note="H->A: Impairs copper-binding." FT /evidence="ECO:0000269|PubMed:21319811" FT MUTAGEN 57 FT /note="E->K: Increases oligomerization." FT /evidence="ECO:0000269|PubMed:25561023" FT MUTAGEN 67..71 FT /note="Missing: Reduces polymerization into amyloid FT fibrils." FT /evidence="ECO:0000269|PubMed:19722699" FT MUTAGEN 71..82 FT /note="Missing: Impairs polymerization into amyloid FT fibrils." FT /evidence="ECO:0000269|PubMed:19722699" FT MUTAGEN 76..77 FT /note="Missing: Impairs polymerization into amyloid FT fibrils." FT /evidence="ECO:0000269|PubMed:19722699" FT MUTAGEN 76 FT /note="Missing: Does not affect polymerization into amyloid FT fibrils." FT MUTAGEN 77 FT /note="Missing: Does not affect polymerization into amyloid FT fibrils." FT /evidence="ECO:0000269|PubMed:19722699" FT MUTAGEN 78 FT /note="Missing: Does not affect polymerization into amyloid FT fibrils." FT /evidence="ECO:0000269|PubMed:19722699" FT MUTAGEN 85..94 FT /note="Missing: Reduces polymerization into amyloid FT fibrils." FT /evidence="ECO:0000269|PubMed:19722699" FT MUTAGEN 125 FT /note="Y->F: Abolishes osmotic stress-induced FT phosphorylation." FT /evidence="ECO:0000269|PubMed:12893833" FT MUTAGEN 133 FT /note="Y->F: No effect on osmotic stress-induced FT phosphorylation." FT /evidence="ECO:0000269|PubMed:12893833" FT MUTAGEN 136 FT /note="Y->F: No effect on osmotic stress-induced FT phosphorylation." FT /evidence="ECO:0000269|PubMed:12893833" FT HELIX 3..11 FT /evidence="ECO:0007829|PDB:3Q25" FT STRAND 15..18 FT /evidence="ECO:0007829|PDB:9OBP" FT HELIX 21..32 FT /evidence="ECO:0007829|PDB:3Q26" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:8A4L" FT STRAND 37..40 FT /evidence="ECO:0007829|PDB:9O4B" FT HELIX 41..44 FT /evidence="ECO:0007829|PDB:3Q27" FT STRAND 45..49 FT /evidence="ECO:0007829|PDB:8PJO" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:8JJV" FT HELIX 56..59 FT /evidence="ECO:0007829|PDB:6I42" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:9FYP" FT HELIX 66..68 FT /evidence="ECO:0007829|PDB:3Q28" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:9KCN" FT STRAND 73..83 FT /evidence="ECO:0007829|PDB:9EUU" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:9OBP" FT STRAND 88..96 FT /evidence="ECO:0007829|PDB:9EUU" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:1XQ8" FT TURN 120..122 FT /evidence="ECO:0007829|PDB:1XQ8" FT TURN 124..126 FT /evidence="ECO:0007829|PDB:1XQ8" FT HELIX 128..132 FT /evidence="ECO:0007829|PDB:2N0A" FT TURN 133..136 FT /evidence="ECO:0007829|PDB:2N0A" SQ SEQUENCE 140 AA; 14460 MW; 6BB2F12128931663 CRC64; MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL GKNEEGAPQE GILEDMPVDP DNEAYEMPSE EGYQDYEPEA //