. "SEQUENCE 919 AA; 100409 MW; 55C5316F250D0480 CRC64;"^^ . "FUNCTION: Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1. SUBUNIT: Homodimer (Probable). Heterodimer of isoform 1 and isoform 2 (Probable). Interacts with SIAH1, SIAH2, SNCA, RNF19A AND PARK2. Isoform 2 has a strong tendency to form aggregates and can sequester isoform 1. SUBCELLULAR LOCATION: Cytoplasm. Note=Detected in cytoplasmic inclusion bodies, together with SNCA. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=6; Name=1; Synonyms=1a; IsoId=Q9Y6H5-1; Sequence=Displayed; Name=2; Synonyms=Synphilin-1A; IsoId=Q9Y6H5-2; Sequence=VSP_038839, VSP_038842, VSP_038845; Name=3; IsoId=Q9Y6H5-3; Sequence=VSP_038840, VSP_038845; Name=4; Synonyms=1b; IsoId=Q9Y6H5-4; Sequence=VSP_038841; Name=5; IsoId=Q9Y6H5-5; Sequence=VSP_038839, VSP_038842; Name=6; Synonyms=1c; IsoId=Q9Y6H5-6; Sequence=VSP_038840, VSP_038843, VSP_038844; TISSUE SPECIFICITY: Detected in brain (at protein level). Widely expressed, with highest levels in brain, heart and placenta. PTM: Ubiquitinated; mediated by SIAH1, SIAH2 or RNF19A and leading to its subsequent proteasomal degradation. In the absence of proteasomal degradation, ubiquitinated SNCAIP accumulates in cytoplasmic inclusion bodies. Isoform 2 is subject to limited ubiquitination that does not lead to proteasomal degradation. DISEASE: Defects in SNCAIP may be a cause of Parkinson disease (PARK) [MIM:168600]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. MISCELLANEOUS: Constructs encoding portions of SNCA and SNCAIP co- transfected in mammalian cells promote cytosolic inclusions resembling the Lewy bodies of Parkinson disease. Coexpression of SNCA, SNCAIP, and PARK2 result in the formation of Lewy body-like. ubiquitin-positive cytosolic inclusions. SNCAIP isoform 2 is particularly aggregatation-prone. Familial mutations in PARK2 disrupt the ubiquitination of SNCAIP and the formation of the ubiquitin-positive inclusions. These results provide a molecular basis for the ubiquitination of Lewy body-associated proteins and link PARK2 and SNCA in a common pathogenic mechanism through their interaction with SNCAIP. SIMILARITY: Contains 6 ANK repeats. WEB RESOURCE: Name=GeneReviews; URL=\"http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SNCAIP\"; GENE SYNONYMS:SNCAIP. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License."^^ . . . . . . . . . . . . . . . "SNCAP_HUMAN"^^ . "SNCAIP"^^ . "Alpha-synuclein-interacting protein"^^ . "Sph1"^^ . . . "MEAPEYLDLDEIDFSDDISYSVTSLKTIPELCRRCDTQNEDRSVSSSSWNCGISTLITNTQKPTGIADVYSKFRPVKRVSPLKHQPETLENNESDDQKNQKVVEYQKGGESDLGPQPQELGPGDGVGGPPGKSSEPSTSLGELEHYDLDMDEILDVPYIKSSQQLASFTKVTSEKRILGLCTTINGLSGKACSTGSSESSSSNMAPFCVLSPVKSPHLRKASAVIHDQHKLSTEETEISPPLVKCGSAYEPENQSKDFLNKTFSDPHGRKVEKTTPDCQLRAFHLQSSAAESKPEEQVSGLNRTSSQGPEERSEYLKKVKSILNIVKEGQISLLPHLAADNLDKIHDENGNNLLHIAASQGHAECLQHLTSLMGEDCLNERNTEKLTPAGLAIKNGQLECVRWMVSETEAIAELSCSKDFPSLIHYAGCYGQEKILLWLLQFMQEQGISLDEVDQDGNSAVHVASQHGYLGCIQTLVEYGANVTMQNHAGEKPSQSAERQGHTLCSRYLVVVETCMSLASQVVKLTKQLKEQTVERVTLQNQLQQFLEAQKSEGKSLPSSPSSPSSPASRKSQWKSPDADDDSVAKSKPGVQEGIQVLGSLSASSRARPKAKDEDSDKILRQLLGKEISENVCTQEKLSLEFQDAQASSRNSKKIPLEKRELKLARLRQLMQRSLSESDTDSNNSEDPKTTPVRKADRPRPQPIVESVESMDSAESLHLMIKKHTLASGGRRFPFSIKASKSLDGHSPSPTSESSEPDLESQYPGSGSIPPNQPSGDPQQPSPDSTAAQKVATSPKSALKSPSSKRRTSQNLKLRVTFEEPVVQMEQPSLELNGEKDKDKGRTLQRTSTSNESGDQLKRPFGAFRSIMETLSGNQNNNNNYQAANQLKTSTLPLTSLGRKTDAKGNPASSASKGKNKAA"^^ . "Synphilin-1"^^ .