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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:122,312,237-122,464,219)mRNA (may differ from genome)Protein (919 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SNCAIP
Diseases sorted by gene-association score: synucleinopathy (10), snca-related parkinson disease (10), dementia, lewy body (10), parkinson disease, late-onset (6), dementia (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.64 RPKM in Cervix - Endocervix
Total median expression: 85.19 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.7094-0.273 Picture PostScript Text
3' UTR -150.40723-0.208 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002110 - Ankyrin_rpt
IPR020683 - Ankyrin_rpt-contain_dom

Pfam Domains:
PF12796 - Ankyrin repeats (3 copies)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2KES - NMR MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  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

Cellular Component:
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0008021 synaptic vesicle
GO:0036464 cytoplasmic ribonucleoprotein granule
GO:0042734 presynaptic membrane
GO:0043025 neuronal cell body


-  Descriptions from all associated GenBank mRNAs
  AK299687 - Homo sapiens cDNA FLJ61370 complete cds, highly similar to Synphilin-1.
DQ227317 - Homo sapiens synphilin-1A (SNCAIP) mRNA, complete cds.
BC094759 - Homo sapiens synuclein, alpha interacting protein, mRNA (cDNA clone MGC:104635 IMAGE:4838145), complete cds.
BC040552 - Homo sapiens synuclein, alpha interacting protein, mRNA (cDNA clone MGC:39814 IMAGE:5298588), complete cds.
AK310835 - Homo sapiens cDNA, FLJ17877.
AK304646 - Homo sapiens cDNA FLJ56291 complete cds, highly similar to Synphilin-1.
AF076929 - Homo sapiens synphilin 1 mRNA, complete cds.
BC033743 - Homo sapiens synuclein, alpha interacting protein, mRNA (cDNA clone MGC:45239 IMAGE:5193089), complete cds.
AK298882 - Homo sapiens cDNA FLJ56226 complete cds, highly similar to Synphilin-1.
AB110788 - Homo sapiens SNCAIP mRNA for synphilin-1a protein, transcript variant a, complete cds.
AB110789 - Homo sapiens SNCAIP mRNA for synphilin-1b protein, transcript variant b, complete cds.
AB110790 - Homo sapiens SNCAIP mRNA for synphilin-1c protein, transcript variant c, complete cds.
AB110791 - Homo sapiens SNCAIP mRNA for synphilin-1d protein, transcript variant d, complete cds.
AB110792 - Homo sapiens SNCAIP mRNA for synphilin-1e protein, transcript variant e, complete cds.
AB110794 - Homo sapiens SNCAIP mRNA for synphilin-1g protein, transcript variant g, complete cds.
AB110793 - Homo sapiens SNCAIP mRNA for synphilin-1f protein, transcript variant f, complete cds.
KJ902001 - Synthetic construct Homo sapiens clone ccsbBroadEn_11395 SNCAIP gene, encodes complete protein.
KR711975 - Synthetic construct Homo sapiens clone CCSBHm_00034396 SNCAIP (SNCAIP) mRNA, encodes complete protein.
JD360315 - Sequence 341339 from Patent EP1572962.
JD192773 - Sequence 173797 from Patent EP1572962.
AK001617 - Homo sapiens cDNA FLJ10755 fis, clone NT2RP3004569, weakly similar to ANKYRIN, BRAIN VARIANT 1.
AK021944 - Homo sapiens cDNA FLJ11882 fis, clone HEMBA1007151, highly similar to Synphilin-1.
JD086333 - Sequence 67357 from Patent EP1572962.
JD539952 - Sequence 520976 from Patent EP1572962.
JD410989 - Sequence 392013 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05012 - Parkinson's disease

BioCarta from NCI Cancer Genome Anatomy Project
h_parkinPathway - Role of Parkin in the Ubiquitin-Proteasomal Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q9Y6H5 (Reactome details) participates in the following event(s):

R-HSA-5658092 SIAH1, SIAH2 bind SNCAIP
R-HSA-5658104 SNCAIP binds alpha-synuclein
R-HSA-5658574 PARK2 binds SNCAIP
R-HSA-977225 Amyloid fiber formation
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: D3DSZ1, ENST00000261368.1, ENST00000261368.10, ENST00000261368.11, ENST00000261368.12, ENST00000261368.2, ENST00000261368.3, ENST00000261368.4, ENST00000261368.5, ENST00000261368.6, ENST00000261368.7, ENST00000261368.8, ENST00000261368.9, NM_005460, Q05BS1, Q1PSC2, Q49AC6, Q504U9, Q6L984, Q6L985, Q6L986, Q9HC59, Q9Y6H5, SNCAP_HUMAN, uc003ksw.1, uc003ksw.2, uc003ksw.3
UCSC ID: ENST00000261368.13
RefSeq Accession: NM_005460
Protein: Q9Y6H5 (aka SNCAP_HUMAN or SNCP_HUMAN)
CCDS: CCDS4131.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.