SYUA_HUMAN
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 03-AUG-2022, entry version 242.
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 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 [37]
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 [38]
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 [39]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 1-57 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 [40]
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 [41]
RP STRUCTURE BY ELECTRON MICROSCOPY (1.41 ANGSTROMS) OF 47-56 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 [42]
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 [43]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS).
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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:28288128, PubMed:30404828,
CC PubMed:20798282, PubMed:26442590). 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). Acts also 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). {ECO:0000250|UniProtKB:O55042,
CC ECO:0000250|UniProtKB:P37377, ECO:0000269|PubMed:15207266,
CC ECO:0000269|PubMed:19762560, ECO:0000269|PubMed:20798282,
CC ECO:0000269|PubMed:21841800, ECO:0000269|PubMed:22854022,
CC ECO:0000269|PubMed:23607618, ECO:0000269|PubMed:27597756,
CC ECO:0000269|PubMed:31034892}.
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=3; 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; 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=50; 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; 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; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-985879, EBI-358545;
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}. Membrane
CC {ECO:0000269|PubMed:24936070}. Nucleus {ECO:0000269|PubMed:12859192,
CC ECO:0000269|PubMed:24936070}. Synapse {ECO:0000269|PubMed:15282274}.
CC Secreted {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 -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/snca/";
CC ---------------------------------------------------------------------------
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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_000345.3. [P37840-1]
DR RefSeq; NP_001139526.1; NM_001146054.1. [P37840-1]
DR RefSeq; NP_001139527.1; NM_001146055.1. [P37840-1]
DR RefSeq; NP_009292.1; NM_007308.2. [P37840-2]
DR RefSeq; XP_011530510.1; XM_011532208.2.
DR RefSeq; XP_016864051.1; XM_017008562.1.
DR RefSeq; XP_016864052.1; XM_017008563.1. [P37840-1]
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; 6FLT; EM; 3.42 A; A/B/C/D/E/F/G/H/I/J=1-121.
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; 7STX; EM; 3.14 A; C=1-5.
DR PDBsum; 1XQ8; -.
DR PDBsum; 2JN5; -.
DR PDBsum; 2KKW; -.
DR PDBsum; 2M55; -.
DR PDBsum; 2N0A; -.
DR PDBsum; 2X6M; -.
DR PDBsum; 3Q25; -.
DR PDBsum; 3Q26; -.
DR PDBsum; 3Q27; -.
DR PDBsum; 3Q28; -.
DR PDBsum; 3Q29; -.
DR PDBsum; 4BXL; -.
DR PDBsum; 4R0U; -.
DR PDBsum; 4R0W; -.
DR PDBsum; 4RIK; -.
DR PDBsum; 4RIL; -.
DR PDBsum; 4ZNN; -.
DR PDBsum; 5CRW; -.
DR PDBsum; 6A6B; -.
DR PDBsum; 6CT7; -.
DR PDBsum; 6CU7; -.
DR PDBsum; 6CU8; -.
DR PDBsum; 6FLT; -.
DR PDBsum; 6H6B; -.
DR PDBsum; 6I42; -.
DR PDBsum; 6L1T; -.
DR PDBsum; 6L1U; -.
DR PDBsum; 6L4S; -.
DR PDBsum; 6LRQ; -.
DR PDBsum; 6OSJ; -.
DR PDBsum; 6OSL; -.
DR PDBsum; 6OSM; -.
DR PDBsum; 6PEO; -.
DR PDBsum; 6PES; -.
DR PDBsum; 6RT0; -.
DR PDBsum; 6RTB; -.
DR PDBsum; 6SST; -.
DR PDBsum; 6SSX; -.
DR PDBsum; 6UFR; -.
DR PDBsum; 6XYO; -.
DR PDBsum; 6XYP; -.
DR PDBsum; 6XYQ; -.
DR PDBsum; 7C1D; -.
DR PDBsum; 7E0F; -.
DR PDBsum; 7L7H; -.
DR PDBsum; 7LC9; -.
DR PDBsum; 7NCA; -.
DR PDBsum; 7NCG; -.
DR PDBsum; 7NCH; -.
DR PDBsum; 7NCI; -.
DR PDBsum; 7NCJ; -.
DR PDBsum; 7NCK; -.
DR PDBsum; 7STX; -.
DR AlphaFoldDB; P37840; -.
DR BMRB; P37840; -.
DR SMR; P37840; -.
DR BioGRID; 112506; 595.
DR CORUM; P37840; -.
DR DIP; DIP-35354N; -.
DR IntAct; P37840; 457.
DR MINT; P37840; -.
DR STRING; 9606.ENSP00000338345; -.
DR BindingDB; P37840; -.
DR ChEMBL; CHEMBL6152; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB02709; Resveratrol.
DR TCDB; 1.C.77.1.1; the synuclein (synuclein) family.
DR GlyConnect; 2893; 1 O-Linked glycan (1 site).
DR GlyGen; P37840; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; P37840; -.
DR MetOSite; P37840; -.
DR PhosphoSitePlus; P37840; -.
DR SwissPalm; P37840; -.
DR BioMuta; SNCA; -.
DR DMDM; 586067; -.
DR EPD; P37840; -.
DR jPOST; P37840; -.
DR MassIVE; P37840; -.
DR MaxQB; P37840; -.
DR PaxDb; P37840; -.
DR PeptideAtlas; P37840; -.
DR PRIDE; P37840; -.
DR ProteomicsDB; 55279; -. [P37840-1]
DR ProteomicsDB; 55280; -. [P37840-2]
DR ProteomicsDB; 55281; -. [P37840-3]
DR TopDownProteomics; P37840-1; -. [P37840-1]
DR ABCD; P37840; 23 sequenced antibodies.
DR Antibodypedia; 14688; 3113 antibodies from 55 providers.
DR DNASU; 6622; -.
DR Ensembl; ENST00000336904.7; ENSP00000338345.3; ENSG00000145335.17. [P37840-1]
DR Ensembl; ENST00000345009.8; ENSP00000343683.4; ENSG00000145335.17. [P37840-2]
DR Ensembl; ENST00000394986.5; ENSP00000378437.1; ENSG00000145335.17. [P37840-1]
DR Ensembl; ENST00000394989.6; ENSP00000378440.2; ENSG00000145335.17. [P37840-3]
DR Ensembl; ENST00000394991.8; ENSP00000378442.4; ENSG00000145335.17. [P37840-1]
DR Ensembl; ENST00000420646.6; ENSP00000396241.2; ENSG00000145335.17. [P37840-2]
DR Ensembl; ENST00000505199.5; ENSP00000421485.1; ENSG00000145335.17. [P37840-3]
DR Ensembl; ENST00000506244.5; ENSP00000422238.1; ENSG00000145335.17. [P37840-1]
DR Ensembl; ENST00000508895.5; ENSP00000426955.1; ENSG00000145335.17. [P37840-1]
DR Ensembl; ENST00000618500.4; ENSP00000484044.1; ENSG00000145335.17. [P37840-3]
DR Ensembl; ENST00000673718.1; ENSP00000500990.1; ENSG00000145335.17. [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 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 neXtProt; NX_P37840; -.
DR NIAGADS; ENSG00000145335; -.
DR OpenTargets; ENSG00000145335; -.
DR Orphanet; 411602; Hereditary late-onset Parkinson disease.
DR Orphanet; 1648; NON RARE IN EUROPE: Dementia with Lewy body.
DR Orphanet; 171695; Parkinsonian-pyramidal syndrome.
DR Orphanet; 2828; Young-onset Parkinson disease.
DR PharmGKB; PA35986; -.
DR VEuPathDB; HostDB:ENSG00000145335; -.
DR eggNOG; ENOG502S0Q7; Eukaryota.
DR GeneTree; ENSGT00950000183175; -.
DR HOGENOM; CLU_129378_1_0_1; -.
DR InParanoid; P37840; -.
DR OMA; VHGVTTX; -.
DR OrthoDB; 1535098at2759; -.
DR PhylomeDB; P37840; -.
DR TreeFam; TF332776; -.
DR PathwayCommons; P37840; -.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P37840; -.
DR SIGNOR; P37840; -.
DR BioGRID-ORCS; 6622; 12 hits in 1072 CRISPR screens.
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 203 other tissues.
DR ExpressionAtlas; P37840; baseline and differential.
DR Genevisible; P37840; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:ParkinsonsUK-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
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:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0099512; C:supramolecular fiber; IDA:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; 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: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:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0070840; F:dynein complex binding; IPI:UniProtKB.
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:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051219; F:phosphoprotein binding; IDA:BHF-UCL.
DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ARUK-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:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:BHF-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; 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:0034599; P:cellular response to oxidative stress; IC:ParkinsonsUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
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:0060079; P:excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0001774; P:microglial cell activation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IEA:Ensembl.
DR GO; GO:0007006; P:mitochondrial membrane organization; IEA:Ensembl.
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:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
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:0035067; P:negative regulation of histone acetylation; IDA: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:0032769; P:negative regulation of monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:ParkinsonsUK-UCL.
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:0006469; P:negative regulation of protein kinase activity; TAS:ARUK-UCL.
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:0032410; P:negative regulation of transporter activity; IDA:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006638; P:neutral lipid metabolic process; IEA:Ensembl.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:Ensembl.
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:1903284; P:positive regulation of glutathione peroxidase activity; IDA:ParkinsonsUK-UCL.
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:1901216; P:positive regulation of neuron death; IDA:ParkinsonsUK-UCL.
DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:BHF-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:0050812; P:regulation of acyl-CoA biosynthetic process; IEA:Ensembl.
DR GO; GO:0014059; P:regulation of dopamine secretion; TAS:UniProtKB.
DR GO; GO:0014048; P:regulation of glutamate secretion; IEA:Ensembl.
DR GO; GO:0040012; P:regulation of locomotion; IEA:Ensembl.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0043030; P:regulation of macrophage activation; IEA:Ensembl.
DR GO; GO:1901214; P:regulation of neuron death; IBA:GO_Central.
DR GO; GO:0051621; P:regulation of norepinephrine uptake; IGI:ARUK-UCL.
DR GO; GO:0010517; P:regulation of phospholipase activity; IDA:UniProtKB.
DR GO; GO:1905606; P:regulation of presynapse assembly; IGI:ParkinsonsUK-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:0022898; P:regulation of transmembrane transporter activity; IGI:ARUK-UCL.
DR GO; GO:0034341; P:response to interferon-gamma; IDA:UniProtKB.
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:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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: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; IEA:Ensembl.
DR DisProt; DP00070; -.
DR IDEAL; IID00302; -.
DR InterPro; IPR001058; Synuclein.
DR InterPro; IPR002460; Synuclein_alpha.
DR PANTHER; PTHR13820; PTHR13820; 1.
DR PANTHER; PTHR13820:SF5; PTHR13820:SF5; 1.
DR Pfam; PF01387; Synuclein; 1.
DR PRINTS; PR01212; ASYNUCLEIN.
DR PRINTS; PR01211; SYNUCLEIN.
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; Reference proteome;
KW 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 116..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 BARK1, 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 stress-
FT 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 16..18
FT /evidence="ECO:0007829|PDB:6XYP"
FT HELIX 21..32
FT /evidence="ECO:0007829|PDB:3Q26"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:6L1T"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:3Q27"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:6OSJ"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:3Q27"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:7E0F"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:3Q28"
FT STRAND 70..86
FT /evidence="ECO:0007829|PDB:6UFR"
FT STRAND 88..97
FT /evidence="ECO:0007829|PDB:6UFR"
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 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
