Q9Y6H5 · SNCAP_HUMAN
- ProteinSynphilin-1
- GeneSNCAIP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids919 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
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 PRKN result in the formation of Lewy body-like. ubiquitin-positive cytosolic inclusions. SNCAIP isoform 2 is particularly aggregation-prone. Familial mutations in PRKN 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 PRKN and SNCA in a common pathogenic mechanism through their interaction with SNCAIP.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoplasmic ribonucleoprotein granule | |
Cellular Component | cytosol | |
Cellular Component | neuronal cell body | |
Cellular Component | nucleoplasm | |
Cellular Component | presynaptic membrane | |
Cellular Component | synaptic vesicle | |
Molecular Function | identical protein binding | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | cell death | |
Biological Process | dopamine metabolic process | |
Biological Process | regulation of inclusion body assembly | |
Biological Process | regulation of neurotransmitter secretion |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSynphilin-1
- Short namesSph1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y6H5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Detected in cytoplasmic inclusion bodies, together with SNCA.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Parkinson disease (PARK)
- Note
- DescriptionA 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.
- See alsoMIM:168600
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_065358 | 44 | in dbSNP:rs56285021 | |||
Sequence: V → A | ||||||
Mutagenesis | 79 | Decreases interaction with SIAH1 and formation of cytoplasmic inclusion bodies; when associated with N-81. | ||||
Sequence: V → N | ||||||
Mutagenesis | 81 | Decreases interaction with SIAH1 and formation of cytoplasmic inclusion bodies; when associated with N-79. | ||||
Sequence: P → N | ||||||
Natural variant | VAR_048312 | 235 | in dbSNP:rs6867105 | |||
Sequence: E → G | ||||||
Natural variant | VAR_025667 | 621 | found in patients with symptoms of Parkinson disease; uncertain significance; reduced number of cytoplasmic inclusions in cells expressing C-621 compared with cells expressing wild-type (wt) protein when subjected to proteasomal inhibition; C-621 transfected cells are more susceptible to staurosporine-induced cell death than cells expressing wt protein; dbSNP:rs28937592 | |||
Sequence: R → C | ||||||
Natural variant | VAR_065359 | 706 | ||||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,225 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000067068 | 1-919 | UniProt | Synphilin-1 | |||
Sequence: MEAPEYLDLDEIDFSDDISYSVTSLKTIPELCRRCDTQNEDRSVSSSSWNCGISTLITNTQKPTGIADVYSKFRPVKRVSPLKHQPETLENNESDDQKNQKVVEYQKGGESDLGPQPQELGPGDGVGGPPGKSSEPSTSLGELEHYDLDMDEILDVPYIKSSQQLASFTKVTSEKRILGLCTTINGLSGKACSTGSSESSSSNMAPFCVLSPVKSPHLRKASAVIHDQHKLSTEETEISPPLVKCGSAYEPENQSKDFLNKTFSDPHGRKVEKTTPDCQLRAFHLQSSAAESKPEEQVSGLNRTSSQGPEERSEYLKKVKSILNIVKEGQISLLPHLAADNLDKIHDENGNNLLHIAASQGHAECLQHLTSLMGEDCLNERNTEKLTPAGLAIKNGQLECVRWMVSETEAIAELSCSKDFPSLIHYAGCYGQEKILLWLLQFMQEQGISLDEVDQDGNSAVHVASQHGYLGCIQTLVEYGANVTMQNHAGEKPSQSAERQGHTLCSRYLVVVETCMSLASQVVKLTKQLKEQTVERVTLQNQLQQFLEAQKSEGKSLPSSPSSPSSPASRKSQWKSPDADDDSVAKSKPGVQEGIQVLGSLSASSRARPKAKDEDSDKILRQLLGKEISENVCTQEKLSLEFQDAQASSRNSKKIPLEKRELKLARLRQLMQRSLSESDTDSNNSEDPKTTPVRKADRPRPQPIVESVESMDSAESLHLMIKKHTLASGGRRFPFSIKASKSLDGHSPSPTSESSEPDLESQYPGSGSIPPNQPSGDPQQPSPDSTAAQKVATSPKSALKSPSSKRRTSQNLKLRVTFEEPVVQMEQPSLELNGEKDKDKGRTLQRTSTSNESGDQLKRPFGAFRSIMETLSGNQNNNNNYQAANQLKTSTLPLTSLGRKTDAKGNPASSASKGKNKAA | |||||||
Modified residue (large scale data) | 299 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in brain (at protein level). Widely expressed, with highest levels in brain, heart and placenta.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (Probable). Heterodimer of isoform 1 and isoform 2 (Probable). Interacts with SIAH1, SIAH2, SNCA, RNF19A and PRKN. Isoform 2 has a strong tendency to form aggregates and can sequester isoform 1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y6H5 | SNCA P37840 | 22 | EBI-717182, EBI-985879 | |
BINARY | Q9Y6H5 | SNCAIP Q9Y6H5 | 5 | EBI-717182, EBI-717182 | |
BINARY | Q9Y6H5-1 | KALRN O60229-2 | 3 | EBI-9075374, EBI-9075360 | |
BINARY | Q9Y6H5-2 | SNCA P37840 | 2 | EBI-15577909, EBI-985879 | |
BINARY | Q9Y6H5-5 | PRKN O60260-5 | 6 | EBI-25880040, EBI-21251460 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, repeat, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 80-99 | Disordered | ||||
Sequence: SPLKHQPETLENNESDDQKN | ||||||
Region | 108-140 | Disordered | ||||
Sequence: GGESDLGPQPQELGPGDGVGGPPGKSSEPSTSL | ||||||
Compositional bias | 287-309 | Polar residues | ||||
Sequence: SSAAESKPEEQVSGLNRTSSQGP | ||||||
Region | 287-313 | Disordered | ||||
Sequence: SSAAESKPEEQVSGLNRTSSQGPEERS | ||||||
Repeat | 349-380 | ANK 1 | ||||
Sequence: NGNNLLHIAASQGHAECLQHLTSLMGEDCLNE | ||||||
Repeat | 384-413 | ANK 2 | ||||
Sequence: EKLTPAGLAIKNGQLECVRWMVSETEAIAE | ||||||
Repeat | 419-448 | ANK 3 | ||||
Sequence: DFPSLIHYAGCYGQEKILLWLLQFMQEQGI | ||||||
Repeat | 456-485 | ANK 4 | ||||
Sequence: DGNSAVHVASQHGYLGCIQTLVEYGANVTM | ||||||
Coiled coil | 515-552 | |||||
Sequence: CMSLASQVVKLTKQLKEQTVERVTLQNQLQQFLEAQKS | ||||||
Compositional bias | 549-573 | Polar residues | ||||
Sequence: AQKSEGKSLPSSPSSPSSPASRKSQ | ||||||
Region | 549-615 | Disordered | ||||
Sequence: AQKSEGKSLPSSPSSPSSPASRKSQWKSPDADDDSVAKSKPGVQEGIQVLGSLSASSRARPKAKDED | ||||||
Repeat | 603-632 | ANK 5 | ||||
Sequence: ASSRARPKAKDEDSDKILRQLLGKEISENV | ||||||
Region | 666-713 | Disordered | ||||
Sequence: RLRQLMQRSLSESDTDSNNSEDPKTTPVRKADRPRPQPIVESVESMDS | ||||||
Compositional bias | 680-702 | Basic and acidic residues | ||||
Sequence: TDSNNSEDPKTTPVRKADRPRPQ | ||||||
Repeat | 699-729 | ANK 6 | ||||
Sequence: PRPQPIVESVESMDSAESLHLMIKKHTLASG | ||||||
Region | 728-919 | Disordered | ||||
Sequence: SGGRRFPFSIKASKSLDGHSPSPTSESSEPDLESQYPGSGSIPPNQPSGDPQQPSPDSTAAQKVATSPKSALKSPSSKRRTSQNLKLRVTFEEPVVQMEQPSLELNGEKDKDKGRTLQRTSTSNESGDQLKRPFGAFRSIMETLSGNQNNNNNYQAANQLKTSTLPLTSLGRKTDAKGNPASSASKGKNKAA | ||||||
Compositional bias | 742-815 | Polar residues | ||||
Sequence: SLDGHSPSPTSESSEPDLESQYPGSGSIPPNQPSGDPQQPSPDSTAAQKVATSPKSALKSPSSKRRTSQNLKLR | ||||||
Compositional bias | 831-845 | Basic and acidic residues | ||||
Sequence: ELNGEKDKDKGRTLQ | ||||||
Compositional bias | 868-919 | Polar residues | ||||
Sequence: METLSGNQNNNNNYQAANQLKTSTLPLTSLGRKTDAKGNPASSASKGKNKAA |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
Q9Y6H5-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Synonyms1a
- Length919
- Mass (Da)100,409
- Last updated2008-07-22 v2
- Checksum55C5316F250D0480
Q9Y6H5-2
- Name2
- SynonymsSynphilin-1A
Q9Y6H5-3
- Name3
Q9Y6H5-4
- Name4
- Synonyms1b
- Differences from canonical
- 335-394: Missing
Q9Y6H5-5
- Name5
Q9Y6H5-6
- Name6
- Synonyms1c
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038839 | 1-366 | in isoform 2 and isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_038840 | 19 | in isoform 3 and isoform 6 | |||
Sequence: S → SDNRSQGNRLQKLGLEDTDREDAMGFGSHRAKLTVVAALGACHCPENE | ||||||
Sequence conflict | 188 | in Ref. 6; AAH40552 | ||||
Sequence: S → F | ||||||
Compositional bias | 287-309 | Polar residues | ||||
Sequence: SSAAESKPEEQVSGLNRTSSQGP | ||||||
Alternative sequence | VSP_038841 | 335-394 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_038842 | 367-394 | in isoform 2 and isoform 5 | |||
Sequence: QHLTSLMGEDCLNERNTEKLTPAGLAIK → MTYLIQSHHSRRSQNCAEDVIRKTKTDQ | ||||||
Alternative sequence | VSP_038843 | 476-541 | in isoform 6 | |||
Sequence: LVEYGANVTMQNHAGEKPSQSAERQGHTLCSRYLVVVETCMSLASQVVKLTKQLKEQTVERVTLQN → RLKIQGTWNGSETCLFTHHFSSYPPISSGLQCQGQEGVLFIPDQVGAATNKQVLFQNQLPETKSSY | ||||||
Alternative sequence | VSP_038844 | 542-919 | in isoform 6 | |||
Sequence: Missing | ||||||
Compositional bias | 549-573 | Polar residues | ||||
Sequence: AQKSEGKSLPSSPSSPSSPASRKSQ | ||||||
Sequence conflict | 614 | in Ref. 6; AAH40552 | ||||
Sequence: E → G | ||||||
Compositional bias | 680-702 | Basic and acidic residues | ||||
Sequence: TDSNNSEDPKTTPVRKADRPRPQ | ||||||
Sequence conflict | 696 | in Ref. 6; AAH40552 | ||||
Sequence: A → G | ||||||
Sequence conflict | 712 | in Ref. 6; AAH94759 | ||||
Sequence: D → G | ||||||
Compositional bias | 742-815 | Polar residues | ||||
Sequence: SLDGHSPSPTSESSEPDLESQYPGSGSIPPNQPSGDPQQPSPDSTAAQKVATSPKSALKSPSSKRRTSQNLKLR | ||||||
Sequence conflict | 801 | in Ref. 6; AAH33743 | ||||
Sequence: S → P | ||||||
Compositional bias | 831-845 | Basic and acidic residues | ||||
Sequence: ELNGEKDKDKGRTLQ | ||||||
Compositional bias | 868-919 | Polar residues | ||||
Sequence: METLSGNQNNNNNYQAANQLKTSTLPLTSLGRKTDAKGNPASSASKGKNKAA | ||||||
Alternative sequence | VSP_038845 | 919 | in isoform 2 and isoform 3 | |||
Sequence: A → EMYSSCINLSSNMLIEEHLCNDTRHNDINRKMKKSYSIKHIAEPESKELFL | ||||||
Sequence conflict | 919 | in Ref. 6; AAH94759 | ||||
Sequence: A → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF076929 EMBL· GenBank· DDBJ | AAD30362.1 EMBL· GenBank· DDBJ | mRNA | ||
AF167306 EMBL· GenBank· DDBJ | AAG17478.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF167301 EMBL· GenBank· DDBJ | AAG17478.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF167302 EMBL· GenBank· DDBJ | AAG17478.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF167303 EMBL· GenBank· DDBJ | AAG17478.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF167304 EMBL· GenBank· DDBJ | AAG17478.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF167305 EMBL· GenBank· DDBJ | AAG17478.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ227317 EMBL· GenBank· DDBJ | ABB51162.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471086 EMBL· GenBank· DDBJ | EAW48889.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB110788 EMBL· GenBank· DDBJ | BAD19017.1 EMBL· GenBank· DDBJ | mRNA | ||
AB110789 EMBL· GenBank· DDBJ | BAD19018.1 EMBL· GenBank· DDBJ | mRNA | ||
AB110790 EMBL· GenBank· DDBJ | BAD19019.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471086 EMBL· GenBank· DDBJ | EAW48890.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC033743 EMBL· GenBank· DDBJ | AAH33743.1 EMBL· GenBank· DDBJ | mRNA | ||
BC040552 EMBL· GenBank· DDBJ | AAH40552.1 EMBL· GenBank· DDBJ | mRNA | ||
BC094759 EMBL· GenBank· DDBJ | AAH94759.1 EMBL· GenBank· DDBJ | mRNA |