Human Gene SNCAIP (ENST00000261368.13) from GENCODE V44
Description: Homo sapiens synuclein alpha interacting protein (SNCAIP), transcript variant 1, mRNA. (from RefSeq NM_005460) RefSeq Summary (NM_005460): This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]. Gencode Transcript: ENST00000261368.13 Gencode Gene: ENSG00000064692.20 Transcript (Including UTRs) Position: hg38 chr5:122,312,237-122,464,219 Size: 151,983 Total Exon Count: 11 Strand: + Coding Region Position: hg38 chr5:122,391,135-122,463,496 Size: 72,362 Coding Exon Count: 10
ID:SNCAP_HUMAN DESCRIPTION: RecName: Full=Synphilin-1; Short=Sph1; AltName: Full=Alpha-synuclein-interacting protein; 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. 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";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y6H5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005515 protein binding GO:0031625 ubiquitin protein ligase binding GO:0042802 identical protein binding
Biological Process: GO:0008219 cell death GO:0042417 dopamine metabolic process GO:0044267 cellular protein metabolic process GO:0046928 regulation of neurotransmitter secretion GO:0090083 regulation of inclusion body assembly