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MGP000215

UniProt Annotations

Entry Information
Gene Namearylsulfatase A
Protein EntryARSA_HUMAN
UniProt IDP15289
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P15289-1; Sequence=Displayed; Name=2; IsoId=P15289-2; Sequence=VSP_046190; Note=No experimental confirmation available.;
Catalytic ActivityA cerebroside 3-sulfate + H(2)O = a cerebroside + sulfate.
CofactorName=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:12888274}; Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:12888274};
DiseaseLeukodystrophy 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. {ECO:0000269|PubMed:10220151, ECO:0000269|PubMed:10381328, ECO:0000269|PubMed:10477432, ECO:0000269|PubMed:10533072, ECO:0000269|PubMed:10751093, ECO:0000269|PubMed:11020646, ECO:0000269|PubMed:11061266, ECO:0000269|PubMed:11456299, ECO:0000269|PubMed:11941485, ECO:0000269|PubMed:1353340, ECO:0000269|PubMed:14517960, ECO:0000269|PubMed:14680985, ECO:0000269|PubMed:15026521, ECO:0000269|PubMed:15326627, ECO:0000269|PubMed:15710861, ECO:0000269|PubMed:1670590, ECO:0000269|PubMed:1673291, ECO:0000269|PubMed:1678251, ECO:0000269|PubMed:18693274, ECO:0000269|PubMed:19606494, ECO:0000269|PubMed:20339381, ECO:0000269|PubMed:21265945, ECO:0000269|PubMed:7581401, ECO:0000269|PubMed:7825603, ECO:0000269|PubMed:7860068, ECO:0000269|PubMed:7902317, ECO:0000269|PubMed:7906588, ECO:0000269|PubMed:7909527, ECO:0000269|PubMed:8095918, ECO:0000269|PubMed:8101038, ECO:0000269|PubMed:8101083, ECO:0000269|PubMed:8104633, ECO:0000269|PubMed:8891236, ECO:0000269|PubMed:9090526, ECO:0000269|PubMed:9272717, ECO:0000269|PubMed:9452102, ECO:0000269|PubMed:9490297, ECO:0000269|PubMed:9600244, ECO:0000269|PubMed:9819708}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseMultiple 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. {ECO:0000269|PubMed:15146462}. 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.
Enzyme RegulationInhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine. {ECO:0000269|PubMed:12888274}.
FunctionHydrolyzes cerebroside sulfate.
MiscellaneousThe metal cofactor was first identified as magnesium ion, based on the structure of the recombinant protein, but when purified from human placenta, the protein contains 1 calcium ion per subunit.
PtmThe 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). {ECO:0000269|PubMed:7628016}.
Sequence CautionSequence=AAB03341.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAH11167.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityBelongs to the sulfatase family. {ECO:0000305}.
Subcellular LocationLysosome.
SubunitHomodimer 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. {ECO:0000269|PubMed:12888274, ECO:0000269|PubMed:1352993, ECO:0000269|PubMed:16368756}.
Web ResourceName=Arylsulfatase A (ARSA); Note=Leiden Open Variation Database (LOVD); URL="http://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=ARSA";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/arsa/";
Web ResourceName=Wikipedia; Note=Arylsulfatase A entry; URL="http://en.wikipedia.org/wiki/Arylsulfatase_A";
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