Sacsin

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Sacsin molecular chaperone
Protein SACS PDB 1iur.png
PDB rendering based on 1iur.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SACS ; ARSACS; DNAJC29; PPP1R138; SPAX6
External IDs OMIM604490 MGI1354724 HomoloGene8653 GeneCards: SACS Gene
RNA expression pattern
PBB GE SACS 213262 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 26278 50720
Ensembl ENSG00000151835 ENSMUSG00000048279
UniProt Q9NZJ4 Q9JLC8
RefSeq (mRNA) NM_001278055 NM_172809
RefSeq (protein) NP_001264984 NP_766397
Location (UCSC) Chr 13:
23.9 – 24.01 Mb
Chr 14:
61.74 – 61.87 Mb
PubMed search [1] [2]

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[edit]

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. 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[edit]

Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is a hereditary progressive neurological disorder that primarily affects people from the Saguenay–Lac-Saint-Jean and Charlevoix regions of Quebec or descendants of native settlers in this region. It is characterized by degeneration of the spinal cord and progressive damage of the peripheral nerves. The disorder is caused by a gene mutation on chromosome 13 (SACS) of the 22 chromosomes that determine characteristics that are not related to sex. This is an autosomal recessive disorder, meaning that both parents must be carriers of the gene in order to have a 25% chance of their child having the disorder at each pregnancy.[4] Mutations of the gene is usually a deletion or replacement of a nucleotide in the SACS gene. The mutation of the SACS gene causes the production of an unstable, poorly functioning SACSIN protein. It is unclear as to how this mutation affects the central nervous system (CNS) and skeletal muscles presenting in the signs and symptoms of ARSACS.[5]

ARSACS is usually diagnosed in early childhood, approximately 12–24 months of age when a child begins to take their first steps. It is a lack of coordination and balance during gait that is first noticed. Children with the disorder take frequent falls and appear to have an unsteady (Ataxic) gait. Some of the signs and symptoms include:[6] Stiffness of the legs, appendicular and trunk ataxia, hollow foot and hand deformities, ataxic dysarthria, distal muscle wasting, horizontal gaze nystagmus, and spasticity.[7]

References[edit]

  1. ^ Engert JC, Dore C, Mercier J, Ge B, Betard C, Rioux JD, Owen C, Berube P, Devon K, Birren B, Melancon SB, Morgan K, Hudson TJ, Richter A (Feb 2000). "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. doi:10.1006/geno.1999.6003. PMID 10610707. 
  2. ^ a b "Entrez Gene: SACS spastic ataxia of Charlevoix-Saguenay (sacsin)". 
  3. ^ Parfitt DA, Michael GJ, Vermeulen EG, Prodromou NV, Webb TR, Gallo JM, Cheetham ME, Nicoll WS, Blatch GL, Chapple JP (May 2009). "The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1". Hum. Mol. Genet. 18 (9): 1556–65. doi:10.1093/hmg/ddp067. PMC 2667285. PMID 19208651. 
  4. ^ "Muscular Dystrophy Canada:Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)". Retrieved 2011-05-12. 
  5. ^ "Genetics Home Reference: SACS". U.S. National Library of Medicine. Retrieved 2011-05-12. 
  6. ^ "Muscular Dystrophy Canada: Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS)". Muscular Dystrophy Canada. Retrieved 2011-05-12. 
  7. ^ "Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay: NCBI". U.S. National Library of Medicine. Retrieved 2011-05-12. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.