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Entry version 210 (13 Feb 2019)
Sequence version 3 (01 Feb 1991)
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Protein

Arylsulfatase A

Gene

ARSA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Hydrolyzes cerebroside sulfate.1 Publication

Miscellaneous

The 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.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Ca2+1 PublicationNote: Binds 1 Ca2+ ion per subunit.1 Publication

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi29CalciumCombined sources1 Publication1
Metal bindingi30CalciumCombined sources1 Publication1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei69Nucleophile1 Publication1
Metal bindingi69Calcium; via 3-oxoalanineCombined sources1 Publication1
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei123Substrate1 Publication1
Active sitei1251 Publication1
Binding sitei150Substrate1 Publication1
Binding sitei229Substrate1 Publication1
Metal bindingi281CalciumCombined sources1 Publication1
Metal bindingi282CalciumCombined sources1 Publication1
Binding sitei302Substrate1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • arylsulfatase activity Source: ProtInc
  • calcium ion binding Source: UniProtKB
  • cerebroside-sulfatase activity Source: Reactome
  • sulfuric ester hydrolase activity Source: MGI

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase
LigandCalcium, Metal-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-1660662 Glycosphingolipid metabolism
R-HSA-1663150 The activation of arylsulfatases
R-HSA-6798695 Neutrophil degranulation

SABIO-RK: Biochemical Reaction Kinetics Database

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SABIO-RKi
P15289

SIGNOR Signaling Network Open Resource

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SIGNORi
P15289

Chemistry databases

SwissLipids knowledge resource for lipid biology

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SwissLipidsi
SLP:000000913

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Arylsulfatase A (EC:3.1.6.81 Publication)
Short name:
ASA
Alternative name(s):
Cerebroside-sulfatase
Cleaved into the following 2 chains:
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ARSA
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 22

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000100299.17

Human Gene Nomenclature Database

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HGNCi
HGNC:713 ARSA

Online Mendelian Inheritance in Man (OMIM)

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MIMi
607574 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P15289

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Lysosome

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Metachromatic leukodystrophy (MLD)42 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease caused by abnormal intralysosomal accumulation of cerebroside-3-sulfate in central and peripheral nervous systems, as well as other organs. MLD is clinically characterized by leukodystrophy, progressive demyelination and a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Decreased arylsulfatase A activity is detected in urine, leukocytes, and fibroblasts of affected individuals. Several forms of the disease can be distinguished according to the age at onset and disease severity: late infantile, juvenile and adult forms, partial cerebroside sulfate deficiency, and pseudoarylsulfatase A deficiency. Individuals with pseudoarylsulfatase A deficiency have low arylsulfatase A activity but lack neurological manifestations and are apparently healthy.
See also OMIM:250100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_05416418A → D in MLD; enzyme activity reduced to 5% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476339Ensembl.1
Natural variantiVAR_05416529D → N in MLD; infantile-onset; causes a severe reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476346Ensembl.1
Natural variantiVAR_05416630D → H in MLD; enzyme activity reduced to 2.4% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476340Ensembl.1
Natural variantiVAR_05416732G → S in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476350Ensembl.1
Natural variantiVAR_06741452L → P in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476357Ensembl.1
Natural variantiVAR_05416868L → P in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476351Ensembl.1
Natural variantiVAR_00724482P → L in MLD; late-infantile-onset. 2 PublicationsCorresponds to variant dbSNP:rs6151411Ensembl.1
Natural variantiVAR_00724584R → Q in MLD; mild. 2 PublicationsCorresponds to variant dbSNP:rs74315458Ensembl.1
Natural variantiVAR_05416984R → W in MLD; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs199476352Ensembl.1
Natural variantiVAR_00724686G → D in MLD; severe; no enzyme residual activity; leads to a decreased stability of the mutant enzyme; causes an arrest of the mutant enzyme polypeptide in a prelysosomal compartment. 2 PublicationsCorresponds to variant dbSNP:rs74315460Ensembl.1
Natural variantiVAR_05417094P → A in MLD; adult form. 1 PublicationCorresponds to variant dbSNP:rs199476353Ensembl.1
Natural variantiVAR_00724795S → N in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476363Ensembl.1
Natural variantiVAR_00724896S → F in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315456Ensembl.1
Natural variantiVAR_00724996S → L in MLD; severe; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476371Ensembl.1
Natural variantiVAR_00725099G → D in MLD; adult type. 2 PublicationsCorresponds to variant dbSNP:rs74315455Ensembl.1
Natural variantiVAR_05417199G → V in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs74315455Ensembl.1
Natural variantiVAR_007251119G → R in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476364Ensembl.1
Natural variantiVAR_007252122G → S in MLD; adult type. 1 PublicationCorresponds to variant dbSNP:rs74315461Ensembl.1
Natural variantiVAR_007253135L → P in MLD. 1 PublicationCorresponds to variant dbSNP:rs121434215Ensembl.1
Natural variantiVAR_007254136P → L in MLD; severe late-infantile type; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs74315462Ensembl.1
Natural variantiVAR_054172136P → S in MLD; late-infantile form. 2 PublicationsCorresponds to variant dbSNP:rs60504011Ensembl.1
Natural variantiVAR_054173137Missing in MLD. 1 Publication1
Natural variantiVAR_067415138H → D in MLD; significantly lower activity than wild-type protein. 1 PublicationCorresponds to variant dbSNP:rs199476358Ensembl.1
Natural variantiVAR_054174143R → G in MLD; juvenile/adult-onset; generates 5% as much activity as the parallel normal control. 1 PublicationCorresponds to variant dbSNP:rs199476373Ensembl.1
Natural variantiVAR_054175148P → L in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476375Ensembl.1
Natural variantiVAR_007255152D → Y in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476365Ensembl.1
Natural variantiVAR_054176153Q → H in MLD; late-infantile form; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476377Ensembl.1
Natural variantiVAR_007256154G → D in MLD. 1 PublicationCorresponds to variant dbSNP:rs74315463Ensembl.1
Natural variantiVAR_054177155P → L in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs74315464Ensembl.1
Natural variantiVAR_007257155P → R in MLD. Corresponds to variant dbSNP:rs74315464Ensembl.1
Natural variantiVAR_054178156C → R in MLD; adult type; enzyme activity reduced to 50% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476348Ensembl.1
Natural variantiVAR_007258167P → R in MLD. Corresponds to variant dbSNP:rs74315465Ensembl.1
Natural variantiVAR_007259169D → N in MLD. Corresponds to variant dbSNP:rs74315466Ensembl.1
Natural variantiVAR_007260172C → Y in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476381Ensembl.1
Natural variantiVAR_007261179I → S in MLD; mild. 5 PublicationsCorresponds to variant dbSNP:rs74315457Ensembl.1
Natural variantiVAR_054179181L → Q in MLD; infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476378Ensembl.1
Natural variantiVAR_054180190Q → H in MLD; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476372Ensembl.1
Natural variantiVAR_054181191P → T in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476374Ensembl.1
Natural variantiVAR_007263201Y → C in MLD; juvenile-onset; results in higly reduced enzyme activity and stability; the mutant enzyme is kept in a prelysosomal compartment. 3 PublicationsCorresponds to variant dbSNP:rs199476345Ensembl.1
Natural variantiVAR_054182212A → P in MLD; loss of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs199476341Ensembl.1
Natural variantiVAR_007264212A → V in MLD. 3 PublicationsCorresponds to variant dbSNP:rs74315467Ensembl.1
Natural variantiVAR_054183217R → H in MLD; enzyme activity reduced to 15.6% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs148403406Ensembl.1
Natural variantiVAR_054184219F → V in MLD; enzyme activity reduced to less than 1% of normal activity. 1 PublicationCorresponds to variant dbSNP:rs199476383Ensembl.1
Natural variantiVAR_007265224A → V in MLD. 1 PublicationCorresponds to variant dbSNP:rs74315468Ensembl.1
Natural variantiVAR_054185227H → Y in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476354Ensembl.1
Natural variantiVAR_007266231P → T in MLD. Corresponds to variant dbSNP:rs74315469Ensembl.1
Natural variantiVAR_007267244R → C in MLD; juvenile-onset. Corresponds to variant dbSNP:rs74315470Ensembl.1
Natural variantiVAR_007268244R → H in MLD; infantile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476366Ensembl.1
Natural variantiVAR_007269245G → R in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315471Ensembl.1
Natural variantiVAR_054186247F → S in MLD. 2 PublicationsCorresponds to variant dbSNP:rs199476384Ensembl.1
Natural variantiVAR_007270250S → Y in MLD; infantile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476367Ensembl.1
Natural variantiVAR_054187253E → K in MLD; late-infantile; decreased enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs74315483Ensembl.1
Natural variantiVAR_054188255D → H in MLD; late-infantile form; no enzyme residual activity; leads to a decreased stability of the mutant enzyme; causes an arrest of the mutant enzyme polypeptide in a prelysosomal compartment. 2 PublicationsCorresponds to variant dbSNP:rs80338819Ensembl.1
Natural variantiVAR_007271274T → M in MLD; severe; 35% of normal activity. 3 PublicationsCorresponds to variant dbSNP:rs74315472Ensembl.1
Natural variantiVAR_054189281D → Y in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476386Ensembl.1
Natural variantiVAR_054190282N → S in MLD; enzyme activity reduced to 0.6% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476342Ensembl.1
Natural variantiVAR_054191286T → P in MLD; adult type. 1 PublicationCorresponds to variant dbSNP:rs28940894Ensembl.1
Natural variantiVAR_007272288R → C in MLD. 1 PublicationCorresponds to variant dbSNP:rs74315473Ensembl.1
Natural variantiVAR_054192288R → H in MLD; adult form. 1 PublicationCorresponds to variant dbSNP:rs199476355Ensembl.1
Natural variantiVAR_054193293G → D in MLD; late-onset. 1 PublicationCorresponds to variant dbSNP:rs199476387Ensembl.1
Natural variantiVAR_054194293G → S in MLD; adult type; causes a severe reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476349Ensembl.1
Natural variantiVAR_054195294C → Y in MLD; juvenile-onset; causes a severe reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476347Ensembl.1
Natural variantiVAR_007273295S → Y in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315474Ensembl.1
Natural variantiVAR_054196298L → S in MLD; late-infantile form; complete loss of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476389Ensembl.1
Natural variantiVAR_008132300C → F in MLD; late-infantile-onset; enzyme activity reduced to less than 1%; the mutant protein is more rapidly degraded in lysosomes; strongly interferes with the octamerization process of the enzyme at low pH. 3 PublicationsCorresponds to variant dbSNP:rs74315484Ensembl.1
Natural variantiVAR_054197302K → N in MLD; enzyme activity reduced to 2.8% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476343Ensembl.1
Natural variantiVAR_067416304T → M in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476359Ensembl.1
Natural variantiVAR_054198306Y → H in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476379Ensembl.1
Natural variantiVAR_067417307E → K in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476360Ensembl.1
Natural variantiVAR_054199308G → D in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476356Ensembl.1
Natural variantiVAR_054200308G → V in MLD; late-infantile form; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476356Ensembl.1
Natural variantiVAR_007274309G → S in MLD; severe; 13% of normal activity. 2 PublicationsCorresponds to variant dbSNP:rs74315459Ensembl.1
Natural variantiVAR_007275311R → Q in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476382Ensembl.1
Natural variantiVAR_054201312E → D in MLD; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476390Ensembl.1
Natural variantiVAR_007276314A → T in MLD; infantile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476368Ensembl.1
Natural variantiVAR_054202325G → S in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs148092995Ensembl.1
Natural variantiVAR_054203327T → I in MLD; late-infantile form. 1 Publication1
Natural variantiVAR_007277335D → V in MLD; late-infantile-onset; loss of enzymatic activity. 5 PublicationsCorresponds to variant dbSNP:rs74315475Ensembl.1
Natural variantiVAR_007279367K → N in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476369Ensembl.1
Natural variantiVAR_007280370R → Q in MLD; mild. Corresponds to variant dbSNP:rs74315477Ensembl.1
Natural variantiVAR_007281370R → W in MLD; severe; no enzyme residual activity. 2 PublicationsCorresponds to variant dbSNP:rs74315476Ensembl.1
Natural variantiVAR_054204376Y → N in MLD; enzyme activity reduced to 4.7% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476344Ensembl.1
Natural variantiVAR_007282377P → L in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315478Ensembl.1
Natural variantiVAR_054205381D → E in MLD; early-infantile form. Corresponds to variant dbSNP:rs6151425Ensembl.1
Natural variantiVAR_007283382E → K in MLD; intermediate. 1 PublicationCorresponds to variant dbSNP:rs74315479Ensembl.1
Natural variantiVAR_007284384R → C in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476370Ensembl.1
Natural variantiVAR_007285390R → Q in MLD; juvenile-onset. 2 PublicationsCorresponds to variant dbSNP:rs199476391Ensembl.1
Natural variantiVAR_007286390R → W in MLD; late-infantile and juvenile-onset. 3 PublicationsCorresponds to variant dbSNP:rs74315480Ensembl.1
Natural variantiVAR_007288397H → Y in MLD; adult-onset. 3 PublicationsCorresponds to variant dbSNP:rs199476376Ensembl.1
Natural variantiVAR_007289398Missing in MLD. 1
Natural variantiVAR_007290406 – 408Missing in MLD; late-infantile-onset. 1 Publication3
Natural variantiVAR_067418406S → G in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476361Ensembl.1
Natural variantiVAR_054206408T → I in MLD; adult type. 1 PublicationCorresponds to variant dbSNP:rs28940895Ensembl.1
Natural variantiVAR_054207409T → I in MLD; mild. 2 PublicationsCorresponds to variant dbSNP:rs74315481Ensembl.1
Natural variantiVAR_008133425P → T in MLD; juvenile-onset; retains about 12% of specific enzyme activity; the mutant protein is unstable; results in more rapid enzyme degradation in lysosomes; addition of the cysteine protease inhibitor leupeptin increases the amount of the enzyme activity; displays a modest reduction in the octamerization process of the enzyme at low pH. 3 PublicationsCorresponds to variant dbSNP:rs74315485Ensembl.1
Natural variantiVAR_007291426P → L in MLD; juvenile/adult-onset; mild; common mutation; decreased enzyme activity. 8 PublicationsCorresponds to variant dbSNP:rs28940893Ensembl.1
Natural variantiVAR_054208428L → P in MLD; late-infantile form. 2 PublicationsCorresponds to variant dbSNP:rs199476392Ensembl.1
Natural variantiVAR_054209429Y → S in MLD; adult-onset. 1 PublicationCorresponds to variant dbSNP:rs199476380Ensembl.1
Natural variantiVAR_054210469A → G in MLD; early-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476385Ensembl.1
Natural variantiVAR_054211489C → G in MLD; late-onset. 1 PublicationCorresponds to variant dbSNP:rs199476388Ensembl.1
Multiple sulfatase deficiency (MSD)1 Publication
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 (PubMed:15146462). SUMF1 mutations result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to 3-oxoalanine (PubMed:7628016).2 Publications
Disease descriptionA 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.
See also OMIM:272200

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi69 – 70CT → TC: Strongly reduces formation of 3-oxoalanine (also known as C-formylglycine, FGly). 1 Publication2
Mutagenesisi69C → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi69C → S: Abolishes formation of 3-oxoalanine (also known as C-formylglycine, FGly). Strongly decreases enzyme activity. 2 Publications1

Keywords - Diseasei

Disease mutation, Ichthyosis, Leukodystrophy, Metachromatic leukodystrophy

Organism-specific databases

DisGeNET

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DisGeNETi
410

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
ARSA

MalaCards human disease database

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MalaCardsi
ARSA
MIMi250100 phenotype
272200 phenotype

Open Targets

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OpenTargetsi
ENSG00000100299

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
309271 Metachromatic leukodystrophy, adult form
309263 Metachromatic leukodystrophy, juvenile form
309256 Metachromatic leukodystrophy, late infantile form
751 NON RARE IN EUROPE: Pseudoarylsulfatase A deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA25005

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2193

Drug and drug target database

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DrugBanki
DB03821 2-Amino-3-Hydroxy-3-Phosphonooxy-Propionic Acid
DB01141 Micafungin
DB04786 Suramin

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
ARSA

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 181 PublicationAdd BLAST18
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000003341719 – 507Arylsulfatase AAdd BLAST489
ChainiPRO_000003341819 – 444Arylsulfatase A component BAdd BLAST426
ChainiPRO_0000033419448 – 507Arylsulfatase A component CAdd BLAST60

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei693-oxoalanine (Cys)2 Publications1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi156 ↔ 172Combined sources1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi158N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Disulfide bondi161 ↔ 168Combined sources1 Publication
Glycosylationi184N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi300 ↔ 414Combined sources1 Publication
Glycosylationi350N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi488 ↔ 500Combined sources1 Publication
Disulfide bondi489 ↔ 502Combined sources1 Publication
Disulfide bondi493 ↔ 499Combined sources1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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).2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P15289

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P15289

MaxQB - The MaxQuant DataBase

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MaxQBi
P15289

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P15289

PeptideAtlas

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PeptideAtlasi
P15289

PRoteomics IDEntifications database

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PRIDEi
P15289

ProteomicsDB human proteome resource

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ProteomicsDBi
53123

PTM databases

GlyConnect protein glycosylation platform

More...
GlyConnecti
61

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P15289

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P15289

UniCarbKB; an annotated and curated database of glycan structures

More...
UniCarbKBi
P15289

Miscellaneous databases

CutDB - Proteolytic event database

More...
PMAP-CutDBi
P15289

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000100299 Expressed in 130 organ(s), highest expression level in right testis

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P15289 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P15289 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB025183
HPA005554

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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 SUMF1.3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
106903, 21 interactors

Protein interaction database and analysis system

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IntActi
P15289, 17 interactors

Molecular INTeraction database

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MINTi
P15289

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000216124

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1507
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AUKX-ray2.10A19-507[»]
1E1ZX-ray2.40P19-507[»]
1E2SX-ray2.35P19-507[»]
1E33X-ray2.50P19-507[»]
1E3CX-ray2.65P19-507[»]
1N2KX-ray2.75A19-507[»]
1N2LX-ray3.20A19-507[»]
2AIJX-ray1.55P69-73[»]
2AIKX-ray1.73P68-74[»]
2HI8X-ray1.64P69-73[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P15289

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P15289

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P15289

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the sulfatase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3867 Eukaryota
COG3119 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000157610

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000135352

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG004283

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P15289

KEGG Orthology (KO)

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KOi
K01134

Database of Orthologous Groups

More...
OrthoDBi
515367at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P15289

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.40.720.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR017849 Alkaline_Pase-like_a/b/a
IPR017850 Alkaline_phosphatase_core_sf
IPR024607 Sulfatase_CS
IPR000917 Sulfatase_N

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00884 Sulfatase, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF53649 SSF53649, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00523 SULFATASE_1, 1 hit
PS00149 SULFATASE_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P15289-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGAPRSLLLA LAAGLAVARP PNIVLIFADD LGYGDLGCYG HPSSTTPNLD
60 70 80 90 100
QLAAGGLRFT DFYVPVSLCT PSRAALLTGR LPVRMGMYPG VLVPSSRGGL
110 120 130 140 150
PLEEVTVAEV LAARGYLTGM AGKWHLGVGP EGAFLPPHQG FHRFLGIPYS
160 170 180 190 200
HDQGPCQNLT CFPPATPCDG GCDQGLVPIP LLANLSVEAQ PPWLPGLEAR
210 220 230 240 250
YMAFAHDLMA DAQRQDRPFF LYYASHHTHY PQFSGQSFAE RSGRGPFGDS
260 270 280 290 300
LMELDAAVGT LMTAIGDLGL LEETLVIFTA DNGPETMRMS RGGCSGLLRC
310 320 330 340 350
GKGTTYEGGV REPALAFWPG HIAPGVTHEL ASSLDLLPTL AALAGAPLPN
360 370 380 390 400
VTLDGFDLSP LLLGTGKSPR QSLFFYPSYP DEVRGVFAVR TGKYKAHFFT
410 420 430 440 450
QGSAHSDTTA DPACHASSSL TAHEPPLLYD LSKDPGENYN LLGGVAGATP
460 470 480 490 500
EVLQALKQLQ LLKAQLDAAV TFGPSQVARG EDPALQICCH PGCTPRPACC

HCPDPHA
Length:507
Mass (Da):53,588
Last modified:February 1, 1991 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3DDBE1378B4176A6
GO
Isoform 2 (identifier: P15289-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Note: No experimental confirmation available.
Show »
Length:423
Mass (Da):44,881
Checksum:iD67E0EE072BEC7BB
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DFZ2A0A0C4DFZ2_HUMAN
Arylsulfatase A
ARSA
509Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
V9GYR0V9GYR0_HUMAN
Arylsulfatase A
ARSA
69Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAB03341 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAH11167 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti290S → P in AK098659 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05416418A → D in MLD; enzyme activity reduced to 5% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476339Ensembl.1
Natural variantiVAR_05416529D → N in MLD; infantile-onset; causes a severe reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476346Ensembl.1
Natural variantiVAR_05416630D → H in MLD; enzyme activity reduced to 2.4% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476340Ensembl.1
Natural variantiVAR_05416732G → S in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476350Ensembl.1
Natural variantiVAR_06741452L → P in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476357Ensembl.1
Natural variantiVAR_05416868L → P in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476351Ensembl.1
Natural variantiVAR_00724376L → P1 PublicationCorresponds to variant dbSNP:rs199476362Ensembl.1
Natural variantiVAR_00724482P → L in MLD; late-infantile-onset. 2 PublicationsCorresponds to variant dbSNP:rs6151411Ensembl.1
Natural variantiVAR_00724584R → Q in MLD; mild. 2 PublicationsCorresponds to variant dbSNP:rs74315458Ensembl.1
Natural variantiVAR_05416984R → W in MLD; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs199476352Ensembl.1
Natural variantiVAR_00724686G → D in MLD; severe; no enzyme residual activity; leads to a decreased stability of the mutant enzyme; causes an arrest of the mutant enzyme polypeptide in a prelysosomal compartment. 2 PublicationsCorresponds to variant dbSNP:rs74315460Ensembl.1
Natural variantiVAR_05417094P → A in MLD; adult form. 1 PublicationCorresponds to variant dbSNP:rs199476353Ensembl.1
Natural variantiVAR_00724795S → N in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476363Ensembl.1
Natural variantiVAR_00724896S → F in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315456Ensembl.1
Natural variantiVAR_00724996S → L in MLD; severe; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476371Ensembl.1
Natural variantiVAR_00725099G → D in MLD; adult type. 2 PublicationsCorresponds to variant dbSNP:rs74315455Ensembl.1
Natural variantiVAR_05417199G → V in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs74315455Ensembl.1
Natural variantiVAR_007251119G → R in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476364Ensembl.1
Natural variantiVAR_007252122G → S in MLD; adult type. 1 PublicationCorresponds to variant dbSNP:rs74315461Ensembl.1
Natural variantiVAR_007253135L → P in MLD. 1 PublicationCorresponds to variant dbSNP:rs121434215Ensembl.1
Natural variantiVAR_007254136P → L in MLD; severe late-infantile type; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs74315462Ensembl.1
Natural variantiVAR_054172136P → S in MLD; late-infantile form. 2 PublicationsCorresponds to variant dbSNP:rs60504011Ensembl.1
Natural variantiVAR_054173137Missing in MLD. 1 Publication1
Natural variantiVAR_067415138H → D in MLD; significantly lower activity than wild-type protein. 1 PublicationCorresponds to variant dbSNP:rs199476358Ensembl.1
Natural variantiVAR_054174143R → G in MLD; juvenile/adult-onset; generates 5% as much activity as the parallel normal control. 1 PublicationCorresponds to variant dbSNP:rs199476373Ensembl.1
Natural variantiVAR_054175148P → L in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476375Ensembl.1
Natural variantiVAR_007255152D → Y in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476365Ensembl.1
Natural variantiVAR_054176153Q → H in MLD; late-infantile form; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476377Ensembl.1
Natural variantiVAR_007256154G → D in MLD. 1 PublicationCorresponds to variant dbSNP:rs74315463Ensembl.1
Natural variantiVAR_054177155P → L in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs74315464Ensembl.1
Natural variantiVAR_007257155P → R in MLD. Corresponds to variant dbSNP:rs74315464Ensembl.1
Natural variantiVAR_054178156C → R in MLD; adult type; enzyme activity reduced to 50% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476348Ensembl.1
Natural variantiVAR_007258167P → R in MLD. Corresponds to variant dbSNP:rs74315465Ensembl.1
Natural variantiVAR_007259169D → N in MLD. Corresponds to variant dbSNP:rs74315466Ensembl.1
Natural variantiVAR_007260172C → Y in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476381Ensembl.1
Natural variantiVAR_007261179I → S in MLD; mild. 5 PublicationsCorresponds to variant dbSNP:rs74315457Ensembl.1
Natural variantiVAR_054179181L → Q in MLD; infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476378Ensembl.1
Natural variantiVAR_054180190Q → H in MLD; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476372Ensembl.1
Natural variantiVAR_054181191P → T in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476374Ensembl.1
Natural variantiVAR_007262193W → C6 PublicationsCorresponds to variant dbSNP:rs6151415Ensembl.1
Natural variantiVAR_007263201Y → C in MLD; juvenile-onset; results in higly reduced enzyme activity and stability; the mutant enzyme is kept in a prelysosomal compartment. 3 PublicationsCorresponds to variant dbSNP:rs199476345Ensembl.1
Natural variantiVAR_054182212A → P in MLD; loss of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs199476341Ensembl.1
Natural variantiVAR_007264212A → V in MLD. 3 PublicationsCorresponds to variant dbSNP:rs74315467Ensembl.1
Natural variantiVAR_054183217R → H in MLD; enzyme activity reduced to 15.6% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs148403406Ensembl.1
Natural variantiVAR_054184219F → V in MLD; enzyme activity reduced to less than 1% of normal activity. 1 PublicationCorresponds to variant dbSNP:rs199476383Ensembl.1
Natural variantiVAR_007265224A → V in MLD. 1 PublicationCorresponds to variant dbSNP:rs74315468Ensembl.1
Natural variantiVAR_054185227H → Y in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476354Ensembl.1
Natural variantiVAR_007266231P → T in MLD. Corresponds to variant dbSNP:rs74315469Ensembl.1
Natural variantiVAR_007267244R → C in MLD; juvenile-onset. Corresponds to variant dbSNP:rs74315470Ensembl.1
Natural variantiVAR_007268244R → H in MLD; infantile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476366Ensembl.1
Natural variantiVAR_007269245G → R in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315471Ensembl.1
Natural variantiVAR_054186247F → S in MLD. 2 PublicationsCorresponds to variant dbSNP:rs199476384Ensembl.1
Natural variantiVAR_007270250S → Y in MLD; infantile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476367Ensembl.1
Natural variantiVAR_054187253E → K in MLD; late-infantile; decreased enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs74315483Ensembl.1
Natural variantiVAR_054188255D → H in MLD; late-infantile form; no enzyme residual activity; leads to a decreased stability of the mutant enzyme; causes an arrest of the mutant enzyme polypeptide in a prelysosomal compartment. 2 PublicationsCorresponds to variant dbSNP:rs80338819Ensembl.1
Natural variantiVAR_007271274T → M in MLD; severe; 35% of normal activity. 3 PublicationsCorresponds to variant dbSNP:rs74315472Ensembl.1
Natural variantiVAR_054189281D → Y in MLD. 1 PublicationCorresponds to variant dbSNP:rs199476386Ensembl.1
Natural variantiVAR_054190282N → S in MLD; enzyme activity reduced to 0.6% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476342Ensembl.1
Natural variantiVAR_054191286T → P in MLD; adult type. 1 PublicationCorresponds to variant dbSNP:rs28940894Ensembl.1
Natural variantiVAR_007272288R → C in MLD. 1 PublicationCorresponds to variant dbSNP:rs74315473Ensembl.1
Natural variantiVAR_054192288R → H in MLD; adult form. 1 PublicationCorresponds to variant dbSNP:rs199476355Ensembl.1
Natural variantiVAR_054193293G → D in MLD; late-onset. 1 PublicationCorresponds to variant dbSNP:rs199476387Ensembl.1
Natural variantiVAR_054194293G → S in MLD; adult type; causes a severe reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476349Ensembl.1
Natural variantiVAR_054195294C → Y in MLD; juvenile-onset; causes a severe reduction of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476347Ensembl.1
Natural variantiVAR_007273295S → Y in MLD; severe. 1 PublicationCorresponds to variant dbSNP:rs74315474Ensembl.1
Natural variantiVAR_054196298L → S in MLD; late-infantile form; complete loss of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs199476389Ensembl.1
Natural variantiVAR_008132300C → F in MLD; late-infantile-onset; enzyme activity reduced to less than 1%; the mutant protein is more rapidly degraded in lysosomes; strongly interferes with the octamerization process of the enzyme at low pH. 3 PublicationsCorresponds to variant dbSNP:rs74315484Ensembl.1
Natural variantiVAR_054197302K → N in MLD; enzyme activity reduced to 2.8% of wild-type enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476343Ensembl.1
Natural variantiVAR_067416304T → M in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476359Ensembl.1
Natural variantiVAR_054198306Y → H in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476379Ensembl.1
Natural variantiVAR_067417307E → K in MLD; loss of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs199476360Ensembl.1
Natural variantiVAR_054199308G → D in MLD; late-infantile form. 1 PublicationCorresponds to variant dbSNP:rs199476356Ensembl.1
Natural variantiVAR_054200308G → V in MLD; late-infantile form; no enzyme residual activity. 1 PublicationCorresponds to variant dbSNP:rs199476356Ensembl.1
Natural variantiVAR_007274309G → S in MLD; severe; 13% of normal activity. 2 PublicationsCorresponds to variant dbSNP:rs74315459Ensembl.1
Natural variantiVAR_007275311R → Q in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476382Ensembl.1
Natural variantiVAR_054201312E → D in MLD; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme. 1 PublicationCorresponds to variant dbSNP:rs199476390Ensembl.1
Natural variantiVAR_007276314A → T in MLD; infantile-onset. 1 PublicationCorresponds to variant dbSNP:rs199476368Ensembl.1
Natural variantiVAR_054202325G → S in MLD; juvenile-onset. 1 PublicationCorresponds to variant dbSNP:rs148092995Ensembl.1
Natural variantiVAR_054203327T → I in MLD; late-infantile form. 1 Publication1
Natural variantiVAR_007277335D → V in MLD; late-infantile-onset; loss of enzymatic activity. 5 PublicationsCorresponds to variant dbSNP:rs74315475Ensembl.1
Natural variantiVAR_007278350N → S Polymorphism; often found in association with a nucleotide substitution in the polyadenylation signal downstream of the stop codon; this association defines an ARSA pseudodeficiency allele found in individuals with low enzymatic activities but no clinical manifestations; no effect on activity; no effect on protein abundance; loss of N-glycosylation. 5 Publications