Description: Homo sapiens spastic ataxia of Charlevoix-Saguenay (sacsin) (SACS), transcript variant 1, mRNA. RefSeq Summary (NM_014363): This gene encodes the sacsin protein, which includes a UbL domain at the N-terminus, a DnaJ domain, and a HEPN domain at the C-terminus. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. This gene includes a very large exon spanning more than 12.8 kb. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. The authors of a publication on the effects of siRNA-mediated sacsin knockdown concluded that sacsin protects against mutant ataxin-1 and suggest that 'the large multi-domain sacsin protein is able to recruit Hsp70 chaperone action and has the potential to regulate the effects of other ataxia proteins' (Parfitt et al., PubMed: 19208651). A pseudogene associated with this gene is located on chromosome 11. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]. Transcript (Including UTRs) Position: hg19 chr13:23,902,962-24,007,867 Size: 104,906 Total Exon Count: 10 Strand: - Coding Region Position: hg19 chr13:23,904,275-23,985,378 Size: 81,104 Coding Exon Count: 9
ID:SACS_HUMAN DESCRIPTION: RecName: Full=Sacsin; AltName: Full=DnaJ homolog subfamily C member 29; Short=DNAJC29; FUNCTION: Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins. SUBCELLULAR LOCATION: Cytoplasm. Note=Predominantly cytoplasmic, a small portion is present in the nucleus and also shows a partial mitochondrial overlap with the mitochondrial marker Hsp60. TISSUE SPECIFICITY: Highly expressed in the central nervous system. Also found in skeletal muscle and at low levels in pancreas. DOMAIN: The ubiquitin-like domain mediates interaction with the proteasome. DOMAIN: The J domain is functional and is shown to stimulate E.coli dnaK ATPase activity. DISEASE: Defects in SACS are the cause of spastic ataxia Charlevoix-Saguenay type (SACS) [MIM:270550]. It is a neurodegenerative disease characterized by early-onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse. SIMILARITY: Contains 1 HEPN domain. SIMILARITY: Contains 1 J domain. SIMILARITY: Contains 1 ubiquitin-like domain. SEQUENCE CAUTION: Sequence=BAC03486.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAH18265.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SACS";
Hemoglobin A, Glycosylated Andrew D Paterson et al. Diabetes 2010, A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose., Diabetes.
[PubMed 19875614]
A major locus for A1C and glucose in individuals with diabetes is near SORCS1. This may influence the design and analysis of genetic studies attempting to identify risk factors for long-term diabetic complications.
Hypothyroidism Nicholas Eriksson et al. PloS one 2012, Novel associations for hypothyroidism include known autoimmune risk loci., PloS one.
[PubMed 22493691]
Interleukin-12 David Melzer et al. PLoS genetics 2008, A genome-wide association study identifies protein quantitative trait loci (pQTLs)., PLoS genetics.
[PubMed 18464913]
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 Q9NZJ4
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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.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
