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Protein

Arylsulfatase A

Gene

ARSA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes cerebroside sulfate.

Catalytic activityi

A cerebroside 3-sulfate + H2O = a cerebroside + sulfate.

Cofactori

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi29Calcium1
Metal bindingi30Calcium1
Metal bindingi69Calcium; via 3-oxoalanine1
Binding sitei123Substrate1
Active sitei1251 Publication1
Binding sitei150Substrate1
Binding sitei229Substrate1
Metal bindingi281Calcium1
Metal bindingi282Calcium1
Binding sitei302Substrate1

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

Complete GO annotation...

Keywordsi

Molecular functionHydrolase
LigandCalcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS02032-MONOMER.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
R-HSA-1663150. The activation of arylsulfatases.
R-HSA-6798695. Neutrophil degranulation.
SABIO-RKP15289.

Chemistry databases

SwissLipidsiSLP:000000913.

Names & Taxonomyi

Protein namesi
Recommended name:
Arylsulfatase A (EC:3.1.6.8)
Short name:
ASA
Alternative name(s):
Cerebroside-sulfatase
Cleaved into the following 2 chains:
Gene namesi
Name:ARSA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:713. ARSA.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • lysosomal lumen Source: Reactome
  • lysosome Source: ProtInc

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Involvement in diseasei

Leukodystrophy metachromatic (MLD)39 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:250100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05416418A → D in MLD; enzyme activity reduced to 5% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763391 PublicationEnsembl.1
Natural variantiVAR_05416529D → N in MLD; infantile-onset; causes a severe reduction of enzyme activity. Corresponds to variant dbSNP:rs1994763461 PublicationEnsembl.1
Natural variantiVAR_05416630D → H in MLD; enzyme activity reduced to 2.4% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763401 PublicationEnsembl.1
Natural variantiVAR_05416732G → S in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763501 PublicationEnsembl.1
Natural variantiVAR_06741452L → P in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763571 PublicationEnsembl.1
Natural variantiVAR_05416868L → P in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763511 PublicationEnsembl.1
Natural variantiVAR_00724482P → L in MLD; late-infantile-onset. Corresponds to variant dbSNP:rs61514112 PublicationsEnsembl.1
Natural variantiVAR_00724584R → Q in MLD; mild. Corresponds to variant dbSNP:rs743154582 PublicationsEnsembl.1
Natural variantiVAR_05416984R → W in MLD; juvenile form. Corresponds to variant dbSNP:rs1994763521 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154602 PublicationsEnsembl.1
Natural variantiVAR_05417094P → A in MLD; adult form. Corresponds to variant dbSNP:rs1994763531 PublicationEnsembl.1
Natural variantiVAR_00724795S → N in MLD. Corresponds to variant dbSNP:rs1994763631 PublicationEnsembl.1
Natural variantiVAR_00724896S → F in MLD; severe. Corresponds to variant dbSNP:rs743154561 PublicationEnsembl.1
Natural variantiVAR_00724996S → L in MLD; severe; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763711 PublicationEnsembl.1
Natural variantiVAR_00725099G → D in MLD; adult type. Corresponds to variant dbSNP:rs743154552 PublicationsEnsembl.1
Natural variantiVAR_05417199G → V in MLD; late-infantile form. Corresponds to variant dbSNP:rs743154551 PublicationEnsembl.1
Natural variantiVAR_007251119G → R in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763641 PublicationEnsembl.1
Natural variantiVAR_007252122G → S in MLD; adult type. Corresponds to variant dbSNP:rs743154611 PublicationEnsembl.1
Natural variantiVAR_007253135L → P in MLD. Corresponds to variant dbSNP:rs1214342151 PublicationEnsembl.1
Natural variantiVAR_007254136P → L in MLD; severe late-infantile type; loss of enzymatic activity. Corresponds to variant dbSNP:rs743154621 PublicationEnsembl.1
Natural variantiVAR_054172136P → S in MLD; late-infantile form. Corresponds to variant dbSNP:rs605040112 PublicationsEnsembl.1
Natural variantiVAR_054173137Missing in MLD. 1 Publication1
Natural variantiVAR_067415138H → D in MLD; significantly lower activity than wild-type protein. Corresponds to variant dbSNP:rs1994763581 PublicationEnsembl.1
Natural variantiVAR_054174143R → G in MLD; juvenile/adult-onset; generates 5% as much activity as the parallel normal control. Corresponds to variant dbSNP:rs1994763731 PublicationEnsembl.1
Natural variantiVAR_054175148P → L in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763751 PublicationEnsembl.1
Natural variantiVAR_007255152D → Y in MLD. Corresponds to variant dbSNP:rs1994763651 PublicationEnsembl.1
Natural variantiVAR_054176153Q → H in MLD; late-infantile form; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763771 PublicationEnsembl.1
Natural variantiVAR_007256154G → D in MLD. Corresponds to variant dbSNP:rs743154631 PublicationEnsembl.1
Natural variantiVAR_054177155P → L in MLD; juvenile-onset. Corresponds to variant dbSNP:rs743154641 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763481 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763811 PublicationEnsembl.1
Natural variantiVAR_007261179I → S in MLD; mild. Corresponds to variant dbSNP:rs743154575 PublicationsEnsembl.1
Natural variantiVAR_054179181L → Q in MLD; infantile form. Corresponds to variant dbSNP:rs1994763781 PublicationEnsembl.1
Natural variantiVAR_054180190Q → H in MLD; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763721 PublicationEnsembl.1
Natural variantiVAR_054181191P → T in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763741 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763453 PublicationsEnsembl.1
Natural variantiVAR_054182212A → P in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763412 PublicationsEnsembl.1
Natural variantiVAR_007264212A → V in MLD. Corresponds to variant dbSNP:rs743154673 PublicationsEnsembl.1
Natural variantiVAR_054183217R → H in MLD; enzyme activity reduced to 15.6% of wild-type enzyme. Corresponds to variant dbSNP:rs1484034061 PublicationEnsembl.1
Natural variantiVAR_054184219F → V in MLD; enzyme activity reduced to less than 1% of normal activity. Corresponds to variant dbSNP:rs1994763831 PublicationEnsembl.1
Natural variantiVAR_007265224A → V in MLD. Corresponds to variant dbSNP:rs743154681 PublicationEnsembl.1
Natural variantiVAR_054185227H → Y in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763541 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763661 PublicationEnsembl.1
Natural variantiVAR_007269245G → R in MLD; severe. Corresponds to variant dbSNP:rs743154711 PublicationEnsembl.1
Natural variantiVAR_054186247F → S in MLD. Corresponds to variant dbSNP:rs1994763842 PublicationsEnsembl.1
Natural variantiVAR_007270250S → Y in MLD; infantile-onset. Corresponds to variant dbSNP:rs1994763671 PublicationEnsembl.1
Natural variantiVAR_054187253E → K in MLD; late-infantile. Corresponds to variant dbSNP:rs743154832 PublicationsEnsembl.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. Corresponds to variant dbSNP:rs803388192 PublicationsEnsembl.1
Natural variantiVAR_007271274T → M in MLD; severe; 35% of normal activity. Corresponds to variant dbSNP:rs743154723 PublicationsEnsembl.1
Natural variantiVAR_054189281D → Y in MLD. Corresponds to variant dbSNP:rs1994763861 PublicationEnsembl.1
Natural variantiVAR_054190282N → S in MLD; enzyme activity reduced to 0.6% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763421 PublicationEnsembl.1
Natural variantiVAR_054191286T → P in MLD; adult type. Corresponds to variant dbSNP:rs289408941 PublicationEnsembl.1
Natural variantiVAR_007272288R → C in MLD. Corresponds to variant dbSNP:rs743154731 PublicationEnsembl.1
Natural variantiVAR_054192288R → H in MLD; adult form. Corresponds to variant dbSNP:rs1994763551 PublicationEnsembl.1
Natural variantiVAR_054193293G → D in MLD; late-onset. Corresponds to variant dbSNP:rs1994763871 PublicationEnsembl.1
Natural variantiVAR_054194293G → S in MLD; adult type; causes a severe reduction of enzyme activity. Corresponds to variant dbSNP:rs1994763491 PublicationEnsembl.1
Natural variantiVAR_054195294C → Y in MLD; juvenile-onset; causes a severe reduction of enzyme activity. Corresponds to variant dbSNP:rs1994763471 PublicationEnsembl.1
Natural variantiVAR_007273295S → Y in MLD; severe. Corresponds to variant dbSNP:rs743154741 PublicationEnsembl.1
Natural variantiVAR_054196298L → S in MLD; late-infantile form; complete loss of enzyme activity. Corresponds to variant dbSNP:rs1994763891 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154843 PublicationsEnsembl.1
Natural variantiVAR_054197302K → N in MLD; enzyme activity reduced to 2.8% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763431 PublicationEnsembl.1
Natural variantiVAR_067416304T → M in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763591 PublicationEnsembl.1
Natural variantiVAR_054198306Y → H in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763791 PublicationEnsembl.1
Natural variantiVAR_067417307E → K in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763601 PublicationEnsembl.1
Natural variantiVAR_054199308G → D in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763561 PublicationEnsembl.1
Natural variantiVAR_054200308G → V in MLD; late-infantile form; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763561 PublicationEnsembl.1
Natural variantiVAR_007274309G → S in MLD; severe; 13% of normal activity. Corresponds to variant dbSNP:rs743154592 PublicationsEnsembl.1
Natural variantiVAR_007275311R → Q in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763821 PublicationEnsembl.1
Natural variantiVAR_054201312E → D in MLD; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme. Corresponds to variant dbSNP:rs1994763901 PublicationEnsembl.1
Natural variantiVAR_007276314A → T in MLD; infantile-onset. Corresponds to variant dbSNP:rs1994763681 PublicationEnsembl.1
Natural variantiVAR_054202325G → S in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1480929951 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154755 PublicationsEnsembl.1
Natural variantiVAR_007279367K → N in MLD. Corresponds to variant dbSNP:rs1994763691 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154762 PublicationsEnsembl.1
Natural variantiVAR_054204376Y → N in MLD; enzyme activity reduced to 4.7% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763441 PublicationEnsembl.1
Natural variantiVAR_007282377P → L in MLD; severe. Corresponds to variant dbSNP:rs743154781 PublicationEnsembl.1
Natural variantiVAR_054205381D → E in MLD; early-infantile form. Corresponds to variant dbSNP:rs6151425Ensembl.1
Natural variantiVAR_007283382E → K in MLD; intermediate. Corresponds to variant dbSNP:rs743154791 PublicationEnsembl.1
Natural variantiVAR_007284384R → C in MLD. Corresponds to variant dbSNP:rs1994763701 PublicationEnsembl.1
Natural variantiVAR_007285390R → Q in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763912 PublicationsEnsembl.1
Natural variantiVAR_007286390R → W in MLD; late-infantile and juvenile-onset. Corresponds to variant dbSNP:rs743154803 PublicationsEnsembl.1
Natural variantiVAR_007288397H → Y in MLD; adult-onset. Corresponds to variant dbSNP:rs1994763763 PublicationsEnsembl.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. Corresponds to variant dbSNP:rs1994763611 PublicationEnsembl.1
Natural variantiVAR_054206408T → I in MLD; adult type. Corresponds to variant dbSNP:rs289408951 PublicationEnsembl.1
Natural variantiVAR_054207409T → I in MLD; mild. Corresponds to variant dbSNP:rs743154812 PublicationsEnsembl.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. Corresponds to variant dbSNP:rs743154853 PublicationsEnsembl.1
Natural variantiVAR_007291426P → L in MLD; juvenile/adult-onset; mild; common mutation. Corresponds to variant dbSNP:rs289408938 PublicationsEnsembl.1
Natural variantiVAR_054208428L → P in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763922 PublicationsEnsembl.1
Natural variantiVAR_054209429Y → S in MLD; adult-onset. Corresponds to variant dbSNP:rs1994763801 PublicationEnsembl.1
Natural variantiVAR_054210469A → G in MLD; early-infantile form. Corresponds to variant dbSNP:rs1994763851 PublicationEnsembl.1
Natural variantiVAR_054211489C → G in MLD; late-onset. Corresponds to variant dbSNP:rs1994763881 PublicationEnsembl.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
Mutagenesisi69C → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi69C → S: Strongly decreases enzyme activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Ichthyosis, Leukodystrophy, Metachromatic leukodystrophy

Organism-specific databases

DisGeNETi410.
MalaCardsiARSA.
MIMi250100. phenotype.
272200. phenotype.
OpenTargetsiENSG00000100299.
Orphaneti309271. Metachromatic leukodystrophy, adult form.
309263. Metachromatic leukodystrophy, juvenile form.
309256. Metachromatic leukodystrophy, late infantile form.
751. Pseudoarylsulfatase A deficiency.
PharmGKBiPA25005.

Chemistry databases

ChEMBLiCHEMBL2193.
DrugBankiDB01141. Micafungin.
DB04786. Suramin.

Polymorphism and mutation databases

BioMutaiARSA.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 181 PublicationAdd BLAST18
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
Modified residuei693-oxoalanine (Cys)1 Publication1
Disulfide bondi156 ↔ 172
Glycosylationi158N-linked (GlcNAc...)2 Publications1
Disulfide bondi161 ↔ 168
Glycosylationi184N-linked (GlcNAc...)1 Publication1
Disulfide bondi300 ↔ 414
Glycosylationi350N-linked (GlcNAc...)1 Publication1
Disulfide bondi488 ↔ 500
Disulfide bondi489 ↔ 502
Disulfide bondi493 ↔ 499

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).1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP15289.
MaxQBiP15289.
PaxDbiP15289.
PeptideAtlasiP15289.
PRIDEiP15289.

PTM databases

UniCarbKBiP15289.

Miscellaneous databases

PMAP-CutDBP15289.

Expressioni

Gene expression databases

BgeeiENSG00000100299.
CleanExiHS_ARSA.
ExpressionAtlasiP15289. baseline and differential.
GenevisibleiP15289. HS.

Organism-specific databases

HPAiCAB025183.
HPA005554.

Interactioni

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

Binary interactionsi

WithEntry#Exp.IntActNotes
TRIP13Q156456EBI-2117357,EBI-358993

Protein-protein interaction databases

BioGridi106903. 21 interactors.
IntActiP15289. 6 interactors.
STRINGi9606.ENSP00000216124.

Structurei

Secondary structure

1507
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 30Combined sources9
Helixi37 – 39Combined sources3
Helixi47 – 54Combined sources8
Beta strandi56 – 63Combined sources8
Beta strandi65 – 68Combined sources4
Helixi69 – 78Combined sources10
Helixi82 – 85Combined sources4
Helixi107 – 112Combined sources6
Turni113 – 115Combined sources3
Beta strandi117 – 122Combined sources6
Helixi130 – 132Combined sources3
Helixi136 – 139Combined sources4
Beta strandi142 – 146Combined sources5
Beta strandi153 – 155Combined sources3
Beta strandi159 – 162Combined sources4
Turni163 – 165Combined sources3
Beta strandi181 – 183Combined sources3
Beta strandi186 – 191Combined sources6
Helixi194 – 196Combined sources3
Helixi197 – 214Combined sources18
Beta strandi219 – 224Combined sources6
Beta strandi229 – 231Combined sources3
Turni236 – 241Combined sources6
Beta strandi242 – 244Combined sources3
Helixi245 – 267Combined sources23
Helixi271 – 273Combined sources3
Beta strandi274 – 282Combined sources9
Helixi286 – 291Combined sources6
Beta strandi304 – 306Combined sources3
Helixi307 – 310Combined sources4
Beta strandi315 – 317Combined sources3
Turni319 – 321Combined sources3
Beta strandi324 – 327Combined sources4
Helixi333 – 335Combined sources3
Helixi336 – 343Combined sources8
Helixi359 – 363Combined sources5
Beta strandi372 – 375Combined sources4
Turni382 – 384Combined sources3
Beta strandi387 – 391Combined sources5
Beta strandi394 – 400Combined sources7
Helixi404 – 406Combined sources3
Beta strandi408 – 410Combined sources3
Helixi412 – 414Combined sources3
Beta strandi421 – 430Combined sources10
Turni431 – 433Combined sources3
Helixi450 – 469Combined sources20
Helixi477 – 479Combined sources3
Helixi483 – 485Combined sources3
Turni496 – 499Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
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[»]
ProteinModelPortaliP15289.
SMRiP15289.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15289.

Family & Domainsi

Sequence similaritiesi

Belongs to the sulfatase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3867. Eukaryota.
COG3119. LUCA.
GeneTreeiENSGT00760000119062.
HOGENOMiHOG000135352.
HOVERGENiHBG004283.
InParanoidiP15289.
KOiK01134.
PhylomeDBiP15289.

Family and domain databases

Gene3Di3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR024607. Sulfatase_CS.
IPR000917. Sulfatase_N.
[Graphical view]
PfamiPF00884. Sulfatase. 1 hit.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.
PROSITEiPS00523. SULFATASE_1. 1 hit.
PS00149. SULFATASE_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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
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.
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Length:423
Mass (Da):44,881
Checksum:iD67E0EE072BEC7BB
GO

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
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. Corresponds to variant dbSNP:rs1994763391 PublicationEnsembl.1
Natural variantiVAR_05416529D → N in MLD; infantile-onset; causes a severe reduction of enzyme activity. Corresponds to variant dbSNP:rs1994763461 PublicationEnsembl.1
Natural variantiVAR_05416630D → H in MLD; enzyme activity reduced to 2.4% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763401 PublicationEnsembl.1
Natural variantiVAR_05416732G → S in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763501 PublicationEnsembl.1
Natural variantiVAR_06741452L → P in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763571 PublicationEnsembl.1
Natural variantiVAR_05416868L → P in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763511 PublicationEnsembl.1
Natural variantiVAR_00724376L → P. Corresponds to variant dbSNP:rs1994763621 PublicationEnsembl.1
Natural variantiVAR_00724482P → L in MLD; late-infantile-onset. Corresponds to variant dbSNP:rs61514112 PublicationsEnsembl.1
Natural variantiVAR_00724584R → Q in MLD; mild. Corresponds to variant dbSNP:rs743154582 PublicationsEnsembl.1
Natural variantiVAR_05416984R → W in MLD; juvenile form. Corresponds to variant dbSNP:rs1994763521 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154602 PublicationsEnsembl.1
Natural variantiVAR_05417094P → A in MLD; adult form. Corresponds to variant dbSNP:rs1994763531 PublicationEnsembl.1
Natural variantiVAR_00724795S → N in MLD. Corresponds to variant dbSNP:rs1994763631 PublicationEnsembl.1
Natural variantiVAR_00724896S → F in MLD; severe. Corresponds to variant dbSNP:rs743154561 PublicationEnsembl.1
Natural variantiVAR_00724996S → L in MLD; severe; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763711 PublicationEnsembl.1
Natural variantiVAR_00725099G → D in MLD; adult type. Corresponds to variant dbSNP:rs743154552 PublicationsEnsembl.1
Natural variantiVAR_05417199G → V in MLD; late-infantile form. Corresponds to variant dbSNP:rs743154551 PublicationEnsembl.1
Natural variantiVAR_007251119G → R in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763641 PublicationEnsembl.1
Natural variantiVAR_007252122G → S in MLD; adult type. Corresponds to variant dbSNP:rs743154611 PublicationEnsembl.1
Natural variantiVAR_007253135L → P in MLD. Corresponds to variant dbSNP:rs1214342151 PublicationEnsembl.1
Natural variantiVAR_007254136P → L in MLD; severe late-infantile type; loss of enzymatic activity. Corresponds to variant dbSNP:rs743154621 PublicationEnsembl.1
Natural variantiVAR_054172136P → S in MLD; late-infantile form. Corresponds to variant dbSNP:rs605040112 PublicationsEnsembl.1
Natural variantiVAR_054173137Missing in MLD. 1 Publication1
Natural variantiVAR_067415138H → D in MLD; significantly lower activity than wild-type protein. Corresponds to variant dbSNP:rs1994763581 PublicationEnsembl.1
Natural variantiVAR_054174143R → G in MLD; juvenile/adult-onset; generates 5% as much activity as the parallel normal control. Corresponds to variant dbSNP:rs1994763731 PublicationEnsembl.1
Natural variantiVAR_054175148P → L in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763751 PublicationEnsembl.1
Natural variantiVAR_007255152D → Y in MLD. Corresponds to variant dbSNP:rs1994763651 PublicationEnsembl.1
Natural variantiVAR_054176153Q → H in MLD; late-infantile form; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763771 PublicationEnsembl.1
Natural variantiVAR_007256154G → D in MLD. Corresponds to variant dbSNP:rs743154631 PublicationEnsembl.1
Natural variantiVAR_054177155P → L in MLD; juvenile-onset. Corresponds to variant dbSNP:rs743154641 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763481 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763811 PublicationEnsembl.1
Natural variantiVAR_007261179I → S in MLD; mild. Corresponds to variant dbSNP:rs743154575 PublicationsEnsembl.1
Natural variantiVAR_054179181L → Q in MLD; infantile form. Corresponds to variant dbSNP:rs1994763781 PublicationEnsembl.1
Natural variantiVAR_054180190Q → H in MLD; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763721 PublicationEnsembl.1
Natural variantiVAR_054181191P → T in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763741 PublicationEnsembl.1
Natural variantiVAR_007262193W → C. Corresponds to variant dbSNP:rs61514156 PublicationsEnsembl.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. Corresponds to variant dbSNP:rs1994763453 PublicationsEnsembl.1
Natural variantiVAR_054182212A → P in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763412 PublicationsEnsembl.1
Natural variantiVAR_007264212A → V in MLD. Corresponds to variant dbSNP:rs743154673 PublicationsEnsembl.1
Natural variantiVAR_054183217R → H in MLD; enzyme activity reduced to 15.6% of wild-type enzyme. Corresponds to variant dbSNP:rs1484034061 PublicationEnsembl.1
Natural variantiVAR_054184219F → V in MLD; enzyme activity reduced to less than 1% of normal activity. Corresponds to variant dbSNP:rs1994763831 PublicationEnsembl.1
Natural variantiVAR_007265224A → V in MLD. Corresponds to variant dbSNP:rs743154681 PublicationEnsembl.1
Natural variantiVAR_054185227H → Y in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763541 PublicationEnsembl.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. Corresponds to variant dbSNP:rs1994763661 PublicationEnsembl.1
Natural variantiVAR_007269245G → R in MLD; severe. Corresponds to variant dbSNP:rs743154711 PublicationEnsembl.1
Natural variantiVAR_054186247F → S in MLD. Corresponds to variant dbSNP:rs1994763842 PublicationsEnsembl.1
Natural variantiVAR_007270250S → Y in MLD; infantile-onset. Corresponds to variant dbSNP:rs1994763671 PublicationEnsembl.1
Natural variantiVAR_054187253E → K in MLD; late-infantile. Corresponds to variant dbSNP:rs743154832 PublicationsEnsembl.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. Corresponds to variant dbSNP:rs803388192 PublicationsEnsembl.1
Natural variantiVAR_007271274T → M in MLD; severe; 35% of normal activity. Corresponds to variant dbSNP:rs743154723 PublicationsEnsembl.1
Natural variantiVAR_054189281D → Y in MLD. Corresponds to variant dbSNP:rs1994763861 PublicationEnsembl.1
Natural variantiVAR_054190282N → S in MLD; enzyme activity reduced to 0.6% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763421 PublicationEnsembl.1
Natural variantiVAR_054191286T → P in MLD; adult type. Corresponds to variant dbSNP:rs289408941 PublicationEnsembl.1
Natural variantiVAR_007272288R → C in MLD. Corresponds to variant dbSNP:rs743154731 PublicationEnsembl.1
Natural variantiVAR_054192288R → H in MLD; adult form. Corresponds to variant dbSNP:rs1994763551 PublicationEnsembl.1
Natural variantiVAR_054193293G → D in MLD; late-onset. Corresponds to variant dbSNP:rs1994763871 PublicationEnsembl.1
Natural variantiVAR_054194293G → S in MLD; adult type; causes a severe reduction of enzyme activity. Corresponds to variant dbSNP:rs1994763491 PublicationEnsembl.1
Natural variantiVAR_054195294C → Y in MLD; juvenile-onset; causes a severe reduction of enzyme activity. Corresponds to variant dbSNP:rs1994763471 PublicationEnsembl.1
Natural variantiVAR_007273295S → Y in MLD; severe. Corresponds to variant dbSNP:rs743154741 PublicationEnsembl.1
Natural variantiVAR_054196298L → S in MLD; late-infantile form; complete loss of enzyme activity. Corresponds to variant dbSNP:rs1994763891 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154843 PublicationsEnsembl.1
Natural variantiVAR_054197302K → N in MLD; enzyme activity reduced to 2.8% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763431 PublicationEnsembl.1
Natural variantiVAR_067416304T → M in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763591 PublicationEnsembl.1
Natural variantiVAR_054198306Y → H in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763791 PublicationEnsembl.1
Natural variantiVAR_067417307E → K in MLD; loss of enzymatic activity. Corresponds to variant dbSNP:rs1994763601 PublicationEnsembl.1
Natural variantiVAR_054199308G → D in MLD; late-infantile form. Corresponds to variant dbSNP:rs1994763561 PublicationEnsembl.1
Natural variantiVAR_054200308G → V in MLD; late-infantile form; no enzyme residual activity. Corresponds to variant dbSNP:rs1994763561 PublicationEnsembl.1
Natural variantiVAR_007274309G → S in MLD; severe; 13% of normal activity. Corresponds to variant dbSNP:rs743154592 PublicationsEnsembl.1
Natural variantiVAR_007275311R → Q in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763821 PublicationEnsembl.1
Natural variantiVAR_054201312E → D in MLD; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme. Corresponds to variant dbSNP:rs1994763901 PublicationEnsembl.1
Natural variantiVAR_007276314A → T in MLD; infantile-onset. Corresponds to variant dbSNP:rs1994763681 PublicationEnsembl.1
Natural variantiVAR_054202325G → S in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1480929951 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154755 PublicationsEnsembl.1
Natural variantiVAR_007278350N → S Associated with arylsulfatase A pseudodeficiency; appears to be responsible for the small size of the enzyme produced by pseudodeficiency fibroblasts because it leads to loss of an N-glycosylation site. Corresponds to variant dbSNP:rs20714215 PublicationsEnsembl.1
Natural variantiVAR_018838356F → V. Corresponds to variant dbSNP:rs61514221 PublicationEnsembl.1
Natural variantiVAR_007279367K → N in MLD. Corresponds to variant dbSNP:rs1994763691 PublicationEnsembl.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. Corresponds to variant dbSNP:rs743154762 PublicationsEnsembl.1
Natural variantiVAR_054204376Y → N in MLD; enzyme activity reduced to 4.7% of wild-type enzyme. Corresponds to variant dbSNP:rs1994763441 PublicationEnsembl.1
Natural variantiVAR_007282377P → L in MLD; severe. Corresponds to variant dbSNP:rs743154781 PublicationEnsembl.1
Natural variantiVAR_054205381D → E in MLD; early-infantile form. Corresponds to variant dbSNP:rs6151425Ensembl.1
Natural variantiVAR_007283382E → K in MLD; intermediate. Corresponds to variant dbSNP:rs743154791 PublicationEnsembl.1
Natural variantiVAR_007284384R → C in MLD. Corresponds to variant dbSNP:rs1994763701 PublicationEnsembl.1
Natural variantiVAR_007285390R → Q in MLD; juvenile-onset. Corresponds to variant dbSNP:rs1994763912 Publications