SNCAP_HUMAN
ID SNCAP_HUMAN Reviewed; 919 AA.
AC Q9Y6H5; D3DSZ1; Q05BS1; Q1PSC2; Q49AC6; Q504U9; Q6L984; Q6L985; Q6L986;
AC Q9HC59;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Synphilin-1;
DE Short=Sph1;
DE AltName: Full=Alpha-synuclein-interacting protein;
GN Name=SNCAIP;
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), INTERACTION WITH SNCA, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND VARIANT ALA-44.
RC TISSUE=Brain;
RX PubMed=10319874; DOI=10.1038/8820;
RA Engelender S., Kaminsky Z., Guo X., Sharp A.H., Amaravi R.K.,
RA Kleiderlein J.J., Margolis R.L., Troncoso J.C., Lanahan A., Worley P.F.,
RA Dawson V.L., Dawson T.M., Ross C.A.;
RT "Synphilin-1 associates with alpha-synuclein and promotes the formation of
RT cytosolic inclusions.";
RL Nat. Genet. 22:110-114(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=10967135; DOI=10.1007/s003350010123;
RA Engelender S., Wanner T., Kleiderlein J.J., Wakabayashi K., Tsuji S.,
RA Takahashi H., Ashworth R., Margolis R.L., Ross C.A.;
RT "Organization of the human synphilin-1 gene, a candidate for Parkinson's
RT disease.";
RL Mamm. Genome 11:763-766(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH SNCA,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16595633; DOI=10.1073/pnas.0509707103;
RA Eyal A., Szargel R., Avraham E., Liani E., Haskin J., Rott R.,
RA Engelender S.;
RT "Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes
RT neuronal death and is present in aggregates from alpha-synucleinopathy
RT patients.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5917-5922(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 6), AND VARIANT ALA-44.
RC TISSUE=Cerebellum, and Testis;
RA Lim M.K., Ohsawa Y., Kawamura T., Asakawa S., Takayanagi A., Minoshima S.,
RA Shimizu N.;
RT "Identification and characterization of alternatively spliced form of human
RT synphilin-1.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 5).
RC TISSUE=Brain, and Testis;
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 [7]
RP INTERACTION WITH PRKN, AND UBIQUITINATION.
RX PubMed=11590439; DOI=10.1038/nm1001-1144;
RA Chung K.K.K., Zhang Y., Lim K.L., Tanaka Y., Huang H., Gao J., Ross C.A.,
RA Dawson V.L., Dawson T.M.;
RT "Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1:
RT implications for Lewy-body formation in Parkinson disease.";
RL Nat. Med. 7:1144-1150(2001).
RN [8]
RP INTERACTION WITH RNF19A, AND UBIQUITINATION.
RX PubMed=12750386; DOI=10.1074/jbc.m302763200;
RA Ito T., Niwa J., Hishikawa N., Ishigaki S., Doyu M., Sobue G.;
RT "Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1.";
RL J. Biol. Chem. 278:29106-29114(2003).
RN [9]
RP INTERACTION WITH SIAH1, AND DEGRADATION.
RX PubMed=14506261; DOI=10.1074/jbc.m306347200;
RA Nagano Y., Yamashita H., Takahashi T., Kishida S., Nakamura T., Iseki E.,
RA Hattori N., Mizuno Y., Kikuchi A., Matsumoto M.;
RT "Siah-1 facilitates ubiquitination and degradation of synphilin-1.";
RL J. Biol. Chem. 278:51504-51514(2003).
RN [10]
RP SUBCELLULAR LOCATION, UBIQUITINATION, PROTEASOMAL DEGRADATION, INTERACTION
RP WITH SIAH1 AND SIAH2, AND MUTAGENESIS OF VAL-79 AND PRO-81.
RX PubMed=15064394; DOI=10.1073/pnas.0401081101;
RA Liani E., Eyal A., Avraham E., Shemer R., Szargel R., Berg D.,
RA Bornemann A., Riess O., Ross C.A., Rott R., Engelender S.;
RT "Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence
RT in cellular inclusions and Lewy bodies imply a role in Parkinson's
RT disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:5500-5505(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH SIAH1.
RX PubMed=19224863; DOI=10.1074/jbc.m805990200;
RA Szargel R., Rott R., Eyal A., Haskin J., Shani V., Balan L., Wolosker H.,
RA Engelender S.;
RT "Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates
RT alpha-synuclein monoubiquitylation and inclusion formation.";
RL J. Biol. Chem. 284:11706-11716(2009).
RN [12]
RP STRUCTURE BY NMR OF 512-557, INTERACTION WITH SNCA, PROMOTION OF INCLUSION
RP BODY FORMATION, AND SUBCELLULAR 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 [13]
RP VARIANT CYS-621, CHARACTERIZATION OF VARIANT CYS-621, AND POSSIBLE
RP INVOLVEMENT IN SUSCEPTIBILITY TO PARKINSON DISEASE.
RX PubMed=12761037; DOI=10.1093/hmg/ddg134;
RA Marx F.P., Holzmann C., Strauss K.M., Li L., Eberhardt O., Gerhardt E.,
RA Cookson M.R., Hernandez D., Farrer M.J., Kachergus J., Engelender S.,
RA Ross C.A., Berger K., Schols L., Schulz J.B., Riess O., Kruger R.;
RT "Identification and functional characterization of a novel R621C mutation
RT in the synphilin-1 gene in Parkinson's disease.";
RL Hum. Mol. Genet. 12:1223-1231(2003).
RN [14]
RP VARIANTS ALA-44; CYS-621 AND GLN-706, AND LACK OF ASSOCIATION WITH
RP PARKINSON DISEASE.
RX PubMed=18366718; DOI=10.1186/1471-2350-9-19;
RA Myhre R., Klungland H., Farrer M.J., Aasly J.O.;
RT "Genetic association study of synphilin-1 in idiopathic Parkinson's
RT disease.";
RL BMC Med. Genet. 9:19-19(2008).
CC -!- FUNCTION: Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and
CC inhibits proteasomal degradation of target proteins. Isoform 2 inhibits
CC autoubiquitination and proteasomal degradation of SIAH1, and thereby
CC increases cellular levels of SIAH. Isoform 2 modulates SNCA
CC monoubiquitination by SIAH1. {ECO:0000269|PubMed:16595633,
CC ECO:0000269|PubMed:19224863}.
CC -!- SUBUNIT: Homodimer (Probable). Heterodimer of isoform 1 and isoform 2
CC (Probable). Interacts with SIAH1, SIAH2, SNCA, RNF19A AND PRKN. Isoform
CC 2 has a strong tendency to form aggregates and can sequester isoform 1.
CC {ECO:0000269|PubMed:10319874, ECO:0000269|PubMed:11590439,
CC ECO:0000269|PubMed:12750386, ECO:0000269|PubMed:14506261,
CC ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16595633,
CC ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:19762560, ECO:0000305}.
CC -!- INTERACTION:
CC Q9Y6H5; P37840: SNCA; NbExp=22; IntAct=EBI-717182, EBI-985879;
CC Q9Y6H5; Q9Y6H5: SNCAIP; NbExp=5; IntAct=EBI-717182, EBI-717182;
CC Q9Y6H5-1; O60229-2: KALRN; NbExp=3; IntAct=EBI-9075374, EBI-9075360;
CC Q9Y6H5-2; P37840: SNCA; NbExp=2; IntAct=EBI-15577909, EBI-985879;
CC Q9Y6H5-5; O60260-5: PRKN; NbExp=6; IntAct=EBI-25880040, EBI-21251460;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10319874,
CC ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16595633,
CC ECO:0000269|PubMed:19762560}. Note=Detected in cytoplasmic inclusion
CC bodies, together with SNCA.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=1a;
CC IsoId=Q9Y6H5-1; Sequence=Displayed;
CC Name=2; Synonyms=Synphilin-1A;
CC IsoId=Q9Y6H5-2; Sequence=VSP_038839, VSP_038842, VSP_038845;
CC Name=3;
CC IsoId=Q9Y6H5-3; Sequence=VSP_038840, VSP_038845;
CC Name=4; Synonyms=1b;
CC IsoId=Q9Y6H5-4; Sequence=VSP_038841;
CC Name=5;
CC IsoId=Q9Y6H5-5; Sequence=VSP_038839, VSP_038842;
CC Name=6; Synonyms=1c;
CC IsoId=Q9Y6H5-6; Sequence=VSP_038840, VSP_038843, VSP_038844;
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level). Widely
CC expressed, with highest levels in brain, heart and placenta.
CC {ECO:0000269|PubMed:10319874, ECO:0000269|PubMed:16595633}.
CC -!- PTM: Ubiquitinated; mediated by SIAH1, SIAH2 or RNF19A and leading to
CC its subsequent proteasomal degradation. In the absence of proteasomal
CC degradation, ubiquitinated SNCAIP accumulates in cytoplasmic inclusion
CC bodies. Isoform 2 is subject to limited ubiquitination that does not
CC lead to proteasomal degradation. {ECO:0000269|PubMed:11590439,
CC ECO:0000269|PubMed:12750386, ECO:0000269|PubMed:15064394}.
CC -!- DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex
CC neurodegenerative disorder characterized by bradykinesia, resting
CC tremor, muscular rigidity and postural instability. Additional features
CC are characteristic postural abnormalities, dysautonomia, dystonic
CC cramps, and dementia. The pathology of Parkinson disease involves the
CC loss of dopaminergic neurons in the substantia nigra and the presence
CC of Lewy bodies (intraneuronal accumulations of aggregated proteins), in
CC surviving neurons in various areas of the brain. The disease is
CC progressive and usually manifests after the age of 50 years, although
CC early-onset cases (before 50 years) are known. The majority of the
CC 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:12761037}. Note=Disease
CC susceptibility may be associated with variants affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: Constructs encoding portions of SNCA and SNCAIP co-
CC transfected in mammalian cells promote cytosolic inclusions resembling
CC the Lewy bodies of Parkinson disease. Coexpression of SNCA, SNCAIP, and
CC PRKN result in the formation of Lewy body-like. ubiquitin-positive
CC cytosolic inclusions. SNCAIP isoform 2 is particularly aggregation-
CC prone. Familial mutations in PRKN disrupt the ubiquitination of SNCAIP
CC and the formation of the ubiquitin-positive inclusions. These results
CC provide a molecular basis for the ubiquitination of Lewy body-
CC associated proteins and link PRKN and SNCA in a common pathogenic
CC mechanism through their interaction with SNCAIP.
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DR EMBL; AF076929; AAD30362.1; -; mRNA.
DR EMBL; AF167306; AAG17478.1; -; Genomic_DNA.
DR EMBL; AF167301; AAG17478.1; JOINED; Genomic_DNA.
DR EMBL; AF167302; AAG17478.1; JOINED; Genomic_DNA.
DR EMBL; AF167303; AAG17478.1; JOINED; Genomic_DNA.
DR EMBL; AF167304; AAG17478.1; JOINED; Genomic_DNA.
DR EMBL; AF167305; AAG17478.1; JOINED; Genomic_DNA.
DR EMBL; DQ227317; ABB51162.1; -; mRNA.
DR EMBL; CH471086; EAW48889.1; -; Genomic_DNA.
DR EMBL; AB110788; BAD19017.1; -; mRNA.
DR EMBL; AB110789; BAD19018.1; -; mRNA.
DR EMBL; AB110790; BAD19019.1; -; mRNA.
DR EMBL; CH471086; EAW48890.1; -; Genomic_DNA.
DR EMBL; BC033743; AAH33743.1; -; mRNA.
DR EMBL; BC040552; AAH40552.1; -; mRNA.
DR EMBL; BC094759; AAH94759.1; -; mRNA.
DR CCDS; CCDS4131.1; -. [Q9Y6H5-1]
DR CCDS; CCDS58964.1; -. [Q9Y6H5-2]
DR CCDS; CCDS78054.1; -. [Q9Y6H5-3]
DR RefSeq; NP_001229864.1; NM_001242935.2. [Q9Y6H5-2]
DR RefSeq; NP_001295029.1; NM_001308100.1. [Q9Y6H5-3]
DR RefSeq; NP_001295034.1; NM_001308105.1. [Q9Y6H5-4]
DR RefSeq; NP_001295035.1; NM_001308106.1.
DR RefSeq; NP_001295036.1; NM_001308107.1. [Q9Y6H5-5]
DR RefSeq; NP_001295037.1; NM_001308108.1.
DR RefSeq; NP_001295038.1; NM_001308109.1.
DR RefSeq; NP_005451.2; NM_005460.3. [Q9Y6H5-1]
DR RefSeq; XP_011542039.1; XM_011543737.2. [Q9Y6H5-3]
DR RefSeq; XP_011542040.1; XM_011543738.2. [Q9Y6H5-3]
DR RefSeq; XP_011542041.1; XM_011543739.1. [Q9Y6H5-3]
DR RefSeq; XP_011542043.1; XM_011543741.2. [Q9Y6H5-3]
DR RefSeq; XP_011542045.1; XM_011543743.2. [Q9Y6H5-3]
DR RefSeq; XP_016865567.1; XM_017010078.1. [Q9Y6H5-3]
DR RefSeq; XP_016865571.1; XM_017010082.1. [Q9Y6H5-1]
DR PDB; 2KES; NMR; -; A=512-557.
DR PDBsum; 2KES; -.
DR AlphaFoldDB; Q9Y6H5; -.
DR BMRB; Q9Y6H5; -.
DR SMR; Q9Y6H5; -.
DR BioGRID; 114986; 35.
DR CORUM; Q9Y6H5; -.
DR DIP; DIP-61155N; -.
DR IntAct; Q9Y6H5; 17.
DR MINT; Q9Y6H5; -.
DR STRING; 9606.ENSP00000261368; -.
DR ChEMBL; CHEMBL1926494; -.
DR iPTMnet; Q9Y6H5; -.
DR PhosphoSitePlus; Q9Y6H5; -.
DR BioMuta; SNCAIP; -.
DR DMDM; 205831000; -.
DR EPD; Q9Y6H5; -.
DR jPOST; Q9Y6H5; -.
DR MassIVE; Q9Y6H5; -.
DR PaxDb; Q9Y6H5; -.
DR PeptideAtlas; Q9Y6H5; -.
DR PRIDE; Q9Y6H5; -.
DR ProteomicsDB; 86680; -. [Q9Y6H5-1]
DR ProteomicsDB; 86681; -. [Q9Y6H5-2]
DR ProteomicsDB; 86682; -. [Q9Y6H5-3]
DR ProteomicsDB; 86683; -. [Q9Y6H5-4]
DR ProteomicsDB; 86684; -. [Q9Y6H5-5]
DR ProteomicsDB; 86685; -. [Q9Y6H5-6]
DR Antibodypedia; 1015; 228 antibodies from 33 providers.
DR DNASU; 9627; -.
DR Ensembl; ENST00000261367.11; ENSP00000261367.7; ENSG00000064692.20. [Q9Y6H5-3]
DR Ensembl; ENST00000261368.13; ENSP00000261368.8; ENSG00000064692.20. [Q9Y6H5-1]
DR Ensembl; ENST00000395469.6; ENSP00000378852.2; ENSG00000064692.20. [Q9Y6H5-6]
DR GeneID; 9627; -.
DR KEGG; hsa:9627; -.
DR MANE-Select; ENST00000261368.13; ENSP00000261368.8; NM_005460.4; NP_005451.2.
DR UCSC; uc003ksw.2; human. [Q9Y6H5-1]
DR CTD; 9627; -.
DR DisGeNET; 9627; -.
DR GeneCards; SNCAIP; -.
DR HGNC; HGNC:11139; SNCAIP.
DR HPA; ENSG00000064692; Tissue enhanced (endometrium, ovary).
DR MalaCards; SNCAIP; -.
DR MIM; 168600; phenotype.
DR MIM; 603779; gene.
DR neXtProt; NX_Q9Y6H5; -.
DR OpenTargets; ENSG00000064692; -.
DR PharmGKB; PA35987; -.
DR VEuPathDB; HostDB:ENSG00000064692; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00390000001485; -.
DR HOGENOM; CLU_012404_0_0_1; -.
DR InParanoid; Q9Y6H5; -.
DR OMA; TCSRYLV; -.
DR OrthoDB; 167171at2759; -.
DR PhylomeDB; Q9Y6H5; -.
DR TreeFam; TF329095; -.
DR PathwayCommons; Q9Y6H5; -.
DR Reactome; R-HSA-977225; Amyloid fiber formation. [Q9Y6H5-2]
DR SignaLink; Q9Y6H5; -.
DR SIGNOR; Q9Y6H5; -.
DR BioGRID-ORCS; 9627; 11 hits in 1073 CRISPR screens.
DR ChiTaRS; SNCAIP; human.
DR EvolutionaryTrace; Q9Y6H5; -.
DR GeneWiki; SNCAIP; -.
DR GenomeRNAi; 9627; -.
DR Pharos; Q9Y6H5; Tbio.
DR PRO; PR:Q9Y6H5; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9Y6H5; protein.
DR Bgee; ENSG00000064692; Expressed in ventricular zone and 173 other tissues.
DR ExpressionAtlas; Q9Y6H5; baseline and differential.
DR Genevisible; Q9Y6H5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043025; C:neuronal cell body; NAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0042734; C:presynaptic membrane; NAS:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; TAS:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0008219; P:cell death; IDA:CACAO.
DR GO; GO:0042417; P:dopamine metabolic process; IDA:MGI.
DR GO; GO:0090083; P:regulation of inclusion body assembly; IDA:BHF-UCL.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IDA:MGI.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR040133; SNCAIP.
DR InterPro; IPR032027; SNCAIP_SNCA-bd.
DR PANTHER; PTHR22882; PTHR22882; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF16700; SNCAIP_SNCA_bd; 1.
DR SMART; SM00248; ANK; 4.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Coiled coil; Cytoplasm;
KW Neurodegeneration; Parkinson disease; Parkinsonism; Reference proteome;
KW Repeat; Ubl conjugation.
FT CHAIN 1..919
FT /note="Synphilin-1"
FT /id="PRO_0000067068"
FT REPEAT 349..380
FT /note="ANK 1"
FT REPEAT 384..413
FT /note="ANK 2"
FT REPEAT 419..448
FT /note="ANK 3"
FT REPEAT 456..485
FT /note="ANK 4"
FT REPEAT 603..632
FT /note="ANK 5"
FT REPEAT 699..729
FT /note="ANK 6"
FT REGION 80..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 108..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 549..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 666..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 728..919
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 515..552
FT /evidence="ECO:0000255"
FT COMPBIAS 287..309
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 680..702
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 742..815
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 831..845
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 868..919
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..366
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16595633"
FT /id="VSP_038839"
FT VAR_SEQ 19
FT /note="S -> SDNRSQGNRLQKLGLEDTDREDAMGFGSHRAKLTVVAALGACHCPEN
FT E (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_038840"
FT VAR_SEQ 335..394
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_038841"
FT VAR_SEQ 367..394
FT /note="QHLTSLMGEDCLNERNTEKLTPAGLAIK -> MTYLIQSHHSRRSQNCAEDV
FT IRKTKTDQ (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16595633"
FT /id="VSP_038842"
FT VAR_SEQ 476..541
FT /note="LVEYGANVTMQNHAGEKPSQSAERQGHTLCSRYLVVVETCMSLASQVVKLTK
FT QLKEQTVERVTLQN -> RLKIQGTWNGSETCLFTHHFSSYPPISSGLQCQGQEGVLFI
FT PDQVGAATNKQVLFQNQLPETKSSY (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_038843"
FT VAR_SEQ 542..919
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_038844"
FT VAR_SEQ 919
FT /note="A -> EMYSSCINLSSNMLIEEHLCNDTRHNDINRKMKKSYSIKHIAEPESK
FT ELFL (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16595633"
FT /id="VSP_038845"
FT VARIANT 44
FT /note="V -> A (in dbSNP:rs56285021)"
FT /evidence="ECO:0000269|PubMed:10319874,
FT ECO:0000269|PubMed:18366718, ECO:0000269|Ref.4"
FT /id="VAR_065358"
FT VARIANT 235
FT /note="E -> G (in dbSNP:rs6867105)"
FT /id="VAR_048312"
FT VARIANT 621
FT /note="R -> C (found in patients with symptoms of Parkinson
FT disease; unknown pathological significance; reduced number
FT of cytoplasmic inclusions in cells expressing C-621
FT compared with cells expressing wild-type (wt) protein when
FT subjected to proteasomal inhibition; C-621 transfected
FT cells are more susceptible to staurosporine-induced cell
FT death than cells expressing wt protein; dbSNP:rs28937592)"
FT /evidence="ECO:0000269|PubMed:12761037,
FT ECO:0000269|PubMed:18366718"
FT /id="VAR_025667"
FT VARIANT 706
FT /note="E -> Q"
FT /evidence="ECO:0000269|PubMed:18366718"
FT /id="VAR_065359"
FT MUTAGEN 79
FT /note="V->N: Decreases interaction with SIAH1 and formation
FT of cytoplasmic inclusion bodies; when associated with N-
FT 81."
FT /evidence="ECO:0000269|PubMed:15064394"
FT MUTAGEN 81
FT /note="P->N: Decreases interaction with SIAH1 and formation
FT of cytoplasmic inclusion bodies; when associated with N-
FT 79."
FT /evidence="ECO:0000269|PubMed:15064394"
FT CONFLICT 188
FT /note="S -> F (in Ref. 6; AAH40552)"
FT /evidence="ECO:0000305"
FT CONFLICT 614
FT /note="E -> G (in Ref. 6; AAH40552)"
FT /evidence="ECO:0000305"
FT CONFLICT 696
FT /note="A -> G (in Ref. 6; AAH40552)"
FT /evidence="ECO:0000305"
FT CONFLICT 712
FT /note="D -> G (in Ref. 6; AAH94759)"
FT /evidence="ECO:0000305"
FT CONFLICT 801
FT /note="S -> P (in Ref. 6; AAH33743)"
FT /evidence="ECO:0000305"
FT CONFLICT 919
FT /note="A -> E (in Ref. 6; AAH94759)"
FT /evidence="ECO:0000305"
FT HELIX 512..554
FT /evidence="ECO:0007829|PDB:2KES"
SQ SEQUENCE 919 AA; 100409 MW; 55C5316F250D0480 CRC64;
MEAPEYLDLD EIDFSDDISY SVTSLKTIPE LCRRCDTQNE DRSVSSSSWN CGISTLITNT
QKPTGIADVY SKFRPVKRVS PLKHQPETLE NNESDDQKNQ KVVEYQKGGE SDLGPQPQEL
GPGDGVGGPP GKSSEPSTSL GELEHYDLDM DEILDVPYIK SSQQLASFTK VTSEKRILGL
CTTINGLSGK ACSTGSSESS SSNMAPFCVL SPVKSPHLRK ASAVIHDQHK LSTEETEISP
PLVKCGSAYE PENQSKDFLN KTFSDPHGRK VEKTTPDCQL RAFHLQSSAA ESKPEEQVSG
LNRTSSQGPE ERSEYLKKVK SILNIVKEGQ ISLLPHLAAD NLDKIHDENG NNLLHIAASQ
GHAECLQHLT SLMGEDCLNE RNTEKLTPAG LAIKNGQLEC VRWMVSETEA IAELSCSKDF
PSLIHYAGCY GQEKILLWLL QFMQEQGISL DEVDQDGNSA VHVASQHGYL GCIQTLVEYG
ANVTMQNHAG EKPSQSAERQ GHTLCSRYLV VVETCMSLAS QVVKLTKQLK EQTVERVTLQ
NQLQQFLEAQ KSEGKSLPSS PSSPSSPASR KSQWKSPDAD DDSVAKSKPG VQEGIQVLGS
LSASSRARPK AKDEDSDKIL RQLLGKEISE NVCTQEKLSL EFQDAQASSR NSKKIPLEKR
ELKLARLRQL MQRSLSESDT DSNNSEDPKT TPVRKADRPR PQPIVESVES MDSAESLHLM
IKKHTLASGG RRFPFSIKAS KSLDGHSPSP TSESSEPDLE SQYPGSGSIP PNQPSGDPQQ
PSPDSTAAQK VATSPKSALK SPSSKRRTSQ NLKLRVTFEE PVVQMEQPSL ELNGEKDKDK
GRTLQRTSTS NESGDQLKRP FGAFRSIMET LSGNQNNNNN YQAANQLKTS TLPLTSLGRK
TDAKGNPASS ASKGKNKAA
