SNCAIP

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. Alternatively spliced transcript variants encoding different isoforms of this gene have been described, but their full-length nature has yet to be determined. [provided by RefSeq]

Full Name

synuclein, alpha 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.

Biological Process

Biological Process cell deathManual Assertion Based On ExperimentIDA:CACAO
Biological Process dopamine metabolic processManual Assertion Based On ExperimentIDA:MGI
Biological Process regulation of inclusion body assemblyManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process regulation of neurotransmitter secretionManual Assertion Based On ExperimentIDA:MGI

Cellular Location

Cytoplasm
Detected in cytoplasmic inclusion bodies, together with SNCA.

Involvement in disease

Parkinson disease (PARK):
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.

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.