Sacsin also known as DnaJ homolog subfamily C member 29 (DNAJC29) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''SACS''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Sacsin is a
Hsp70
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an import ...
co-chaperone
Co-chaperones are proteins that assist chaperones in protein folding and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by Hsp70 and Hsp90. They are particularly essential in stimulation ...
.
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
In molecular biology, chaperone DnaJ, also known as Hsp40 (heat shock protein 40 kD), is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.
Function
Molecular chaperones are a diverse family ...
region upstream of the HEPN domain. This modular protein is essential for normal mitochondrial network organization.
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
Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.
Cerebellar ataxia can occur as a result of many diseases and may present with symptom ...
with
spasticity
Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles ...
and
peripheral neuropathy
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
.
Clinical significance
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare
neurodegenerative
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
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.
References
Further reading
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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
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Co-chaperones