Biology:Sacsin
 Generic protein structure example |
Sacsin also known as DnaJ homolog subfamily C member 29 (DNAJC29) is a protein that in humans is encoded by the SACS gene.[1][2] Sacsin is a Hsp70 co-chaperone.[3]
Function
This gene consists of nine exons including a gigantic exon spanning more than 12.8k bp. It encodes the sacsin protein, which includes a UBQ region at the N-terminus, a HEPN domain at the C-terminus and a DnaJ region upstream of the HEPN domain. This modular protein is essential for normal mitochondrial network organization.[4] The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. 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.[2]
Clinical significance
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare neurodegenerative genetic disorder that results from mutations in the gene that produces Sacsin. Afflicted persons suffer from loss of balance, loss of muscle control and spasticity.[5]
References
- ↑ "Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11". Genomics 62 (2): 156–64. December 1999. doi:10.1006/geno.1999.6003. PMID 10610707.
- ↑ 2.0 2.1 "Entrez Gene: SACS spastic ataxia of Charlevoix-Saguenay (sacsin)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=26278.
- ↑ "The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1". Human Molecular Genetics 18 (9): 1556–65. May 2009. doi:10.1093/hmg/ddp067. PMID 19208651.
- ↑ "A reduction in Drp1-mediated fission compromises mitochondrial health in autosomal recessive spastic ataxia of Charlevoix Saguenay". Human Molecular Genetics 25 (15): 3232–3244. June 2016. doi:10.1093/hmg/ddw173. PMID 27288452.
- ↑ "ARSACS" (in en). https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay. Retrieved 19 January 2017.
Further reading
- "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research 5 (5): 277–86. October 1998. doi:10.1093/dnares/5.5.277. PMID 9872452.
- "ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF". Nature Genetics 24 (2): 120–5. February 2000. doi:10.1038/72769. PMID 10655055.
- "Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay". Genetic Testing 5 (3): 255–9. 2001. doi:10.1089/10906570152742326. PMID 11788093.
- "A novel mutation in SACS gene in a family from southern Italy". Neurology 62 (1): 100–2. January 2004. doi:10.1212/wnl.62.1.100. PMID 14718706.
- "Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay type". Neurology 62 (1): 103–6. January 2004. doi:10.1212/01.wnl.0000104491.66816.77. PMID 14718707.
- "Identification of a SACS gene missense mutation in ARSACS". Neurology 62 (1): 107–9. January 2004. doi:10.1212/01.wnl.0000099371.14478.73. PMID 14718708.
- "Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey". Neurogenetics 5 (3): 165–70. September 2004. doi:10.1007/s10048-004-0179-y. PMID 15156359.
- "A phenotype without spasticity in sacsin-related ataxia". Neurology 64 (12): 2129–31. June 2005. doi:10.1212/01.WNL.0000166031.91514.B3. PMID 15985586.
- "Novel compound heterozygous mutations in sacsin-related ataxia". Journal of the Neurological Sciences 239 (1): 101–4. December 2005. doi:10.1016/j.jns.2005.08.005. PMID 16198375.
- "Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon". Neurology 66 (7): 1103–4. April 2006. doi:10.1212/01.wnl.0000204300.94261.ea. PMID 16606928.
- "New mutation in the non-gigantic exon of SACS in Japanese siblings". Movement Disorders 22 (5): 748–9. April 2007. doi:10.1002/mds.21365. PMID 17290461.
External links
- GeneReviews/NCBI/NIH/UW entry on ARSACS - Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
- OMIM entries on ARSACS - Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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