The protein encoded by ARSA gene hydrolyzes cerebroside sulfate to cerebroside and sulfate. Defects in ARSA gene lead to metachromatic leucodystrophy (MLD), a progressive demyelination disease which results in a variety of neurological symptoms and ultimately death. Alternatively spliced transcript variants have been described for ARSA gene. [provided by RefSeq, Dec 2010]
OMIM-Description for Arylsulfatase A / ARSAN
The ARSA gene encodes the lysosomal enzyme arylsulfatase A.
Arylsulfatase A / ARSA
Arylsulfatase A (or cerebroside-sulfatase) is an enzyme that breaks down cerebroside 3-sulfate into cerebroside and sulfate. In humans, arylsulfatase A is encoded by the ARSA gene.
The conversion to 3-oxoalanine (also known as C- formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. This post-translational modification is severely defective in multiple sulfatase deficiency (MSD).
Homodimer at neutral pH and homooctamer at acidic pH. Exists both as a single chain of 58 kDa (component A) or as a chain of 50 kDa (component B) linked by disulfide bond(s) to a 7 kDa chain (component C). Interacts with SUMF1.
A cerebroside 3-sulfate + H(2)O = a cerebroside + sulfate.
Binds 1 calcium ion per subunit.
Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine.
Involvement in disease
Leukodystrophy metachromatic (MLD) [MIM:250100]: A leukodystrophy due to a lysosomal storage defect. Characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non- neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and adult. Note=The disease is caused by mutations affecting the gene represented in this entry. Multiple sulfatase deficiency (MSD) [MIM:272200]: A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post- translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. Note=The protein represented in this entry is involved in disease pathogenesis. Arylsulfatase A activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to 3- oxoalanine.