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P15289 (ARSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Arylsulfatase A

Short name=ASA
EC=3.1.6.8
Alternative name(s):
Cerebroside-sulfatase

Cleaved into the following 2 chains:

  1. Arylsulfatase A component B
  2. Arylsulfatase A component C
Gene names
Name:ARSA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length507 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes cerebroside sulfate.

Catalytic activity

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

Cofactor

Binds 1 calcium ion per subunit. Ref.15

Enzyme regulation

Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine. Ref.15

Subunit structure

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. Ref.9 Ref.13 Ref.15

Subcellular location

Lysosome.

Post-translational modification

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).

Involvement in disease

Leukodystrophy metachromatic (MLD) [MIM:250100]: A leukodystrophy due to a lysosomal storage defect. Characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and adult.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.41 Ref.42 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63

Multiple sulfatase deficiency (MSD) [MIM:272200]: A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
Note: The protein represented in this entry is involved in disease pathogenesis. Arylsulfatase A activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to 3-oxoalanine. Ref.10 Ref.11

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.

Sequence similarities

Belongs to the sulfatase family.

Sequence caution

The sequence AAB03341.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAH11167.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Ichthyosis
Leukodystrophy
Metachromatic leukodystrophy
   DomainSignal
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processautophagy

Inferred from electronic annotation. Source: Ensembl

binding of sperm to zona pellucida

Inferred from electronic annotation. Source: Ensembl

cellular protein metabolic process

Traceable author statement. Source: Reactome

central nervous system development

Inferred from electronic annotation. Source: Ensembl

glycosphingolipid metabolic process

Traceable author statement. Source: Reactome

post-translational protein modification

Traceable author statement. Source: Reactome

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to methylmercury

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to pH

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentacrosomal vesicle

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

endosome

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: Ensembl

extrinsic component of external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: Ensembl

lysosomal lumen

Traceable author statement. Source: Reactome

lysosome

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionarylsulfatase activity

Traceable author statement Ref.1. Source: ProtInc

calcium ion binding

Inferred from direct assay Ref.15. Source: UniProtKB

cerebroside-sulfatase activity

Traceable author statement. Source: Reactome

sulfuric ester hydrolase activity

Inferred from direct assay PubMed 15962010. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P15289-1)

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.
Isoform 2 (identifier: P15289-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.9
Chain19 – 507489Arylsulfatase A
PRO_0000033417
Chain19 – 444426Arylsulfatase A component B
PRO_0000033418
Chain448 – 50760Arylsulfatase A component C
PRO_0000033419

Sites

Active site1251 Ref.15
Metal binding291Calcium
Metal binding301Calcium
Metal binding691Calcium; via 3-oxoalanine
Metal binding2811Calcium
Metal binding2821Calcium
Binding site1231Substrate
Binding site1501Substrate
Binding site2291Substrate
Binding site3021Substrate

Amino acid modifications

Modified residue6913-oxoalanine (Cys)
Glycosylation1581N-linked (GlcNAc...) Ref.12 Ref.15
Glycosylation1841N-linked (GlcNAc...) Ref.15
Glycosylation3501N-linked (GlcNAc...) Ref.12
Disulfide bond156 ↔ 172
Disulfide bond161 ↔ 168
Disulfide bond300 ↔ 414
Disulfide bond488 ↔ 500
Disulfide bond489 ↔ 502
Disulfide bond493 ↔ 499

Natural variations

Alternative sequence1 – 8484Missing in isoform 2.
VSP_046190
Natural variant181A → D in MLD; enzyme activity reduced to 5% of wild-type enzyme. Ref.60
Corresponds to variant rs199476339 [ dbSNP | Ensembl ].
VAR_054164
Natural variant291D → N in MLD; infantile-onset; causes a severe reduction of enzyme activity. Ref.57
Corresponds to variant rs199476346 [ dbSNP | Ensembl ].
VAR_054165
Natural variant301D → H in MLD; enzyme activity reduced to 2.4% of wild-type enzyme. Ref.60
Corresponds to variant rs199476340 [ dbSNP | Ensembl ].
VAR_054166
Natural variant321G → S in MLD; late-infantile form. Ref.45
Corresponds to variant rs199476350 [ dbSNP | Ensembl ].
VAR_054167
Natural variant521L → P in MLD; loss of enzymatic activity. Ref.61
Corresponds to variant rs199476357 [ dbSNP | Ensembl ].
VAR_067414
Natural variant681L → P in MLD; late-infantile form. Ref.45
Corresponds to variant rs199476351 [ dbSNP | Ensembl ].
VAR_054168
Natural variant761L → P. Ref.43
Corresponds to variant rs199476362 [ dbSNP | Ensembl ].
VAR_007243
Natural variant821P → L in MLD; late-infantile-onset. Ref.6 Ref.32
Corresponds to variant rs6151411 [ dbSNP | Ensembl ].
VAR_007244
Natural variant841R → Q in MLD; mild. Ref.22 Ref.60
Corresponds to variant rs74315458 [ dbSNP | Ensembl ].
VAR_007245
Natural variant841R → W in MLD; juvenile form. Ref.45
Corresponds to variant rs199476352 [ dbSNP | Ensembl ].
VAR_054169
Natural variant861G → 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. Ref.30 Ref.48
Corresponds to variant rs74315460 [ dbSNP | Ensembl ].
VAR_007246
Natural variant941P → A in MLD; adult form. Ref.45
Corresponds to variant rs199476353 [ dbSNP | Ensembl ].
VAR_054170
Natural variant951S → N in MLD. Ref.36
Corresponds to variant rs199476363 [ dbSNP | Ensembl ].
VAR_007247
Natural variant961S → F in MLD; severe. Ref.20
Corresponds to variant rs74315456 [ dbSNP | Ensembl ].
VAR_007248
Natural variant961S → L in MLD; severe; no enzyme residual activity. Ref.30
Corresponds to variant rs199476371 [ dbSNP | Ensembl ].
VAR_007249
Natural variant991G → D in MLD; adult type. Ref.19 Ref.63
Corresponds to variant rs74315455 [ dbSNP | Ensembl ].
VAR_007250
Natural variant991G → V in MLD; late-infantile form. Ref.45
Corresponds to variant rs74315455 [ dbSNP | Ensembl ].
VAR_054171
Natural variant1191G → R in MLD; juvenile-onset. Ref.36
Corresponds to variant rs199476364 [ dbSNP | Ensembl ].
VAR_007251
Natural variant1221G → S in MLD; adult type. Ref.26
Corresponds to variant rs74315461 [ dbSNP | Ensembl ].
VAR_007252
Natural variant1351L → P in MLD. Ref.38
Corresponds to variant rs121434215 [ dbSNP | Ensembl ].
VAR_007253
Natural variant1361P → L in MLD; severe late-infantile type; loss of enzymatic activity. Ref.31
Corresponds to variant rs74315462 [ dbSNP | Ensembl ].
VAR_007254
Natural variant1361P → S in MLD; late-infantile form. Ref.45 Ref.56
Corresponds to variant rs60504011 [ dbSNP | Ensembl ].
VAR_054172
Natural variant1371Missing in MLD. Ref.60
VAR_054173
Natural variant1381H → D in MLD; significantly lower activity than wild-type protein. Ref.61
Corresponds to variant rs199476358 [ dbSNP | Ensembl ].
VAR_067415
Natural variant1431R → G in MLD; juvenile/adult-onset; generates 5% as much activity as the parallel normal control. Ref.50
Corresponds to variant rs199476373 [ dbSNP | Ensembl ].
VAR_054174
Natural variant1481P → L in MLD; juvenile-onset. Ref.47
Corresponds to variant rs199476375 [ dbSNP | Ensembl ].
VAR_054175
Natural variant1521D → Y in MLD. Ref.36
Corresponds to variant rs199476365 [ dbSNP | Ensembl ].
VAR_007255
Natural variant1531Q → H in MLD; late-infantile form; no enzyme residual activity. Ref.33
Corresponds to variant rs199476377 [ dbSNP | Ensembl ].
VAR_054176
Natural variant1541G → D in MLD. Ref.60
Corresponds to variant rs74315463 [ dbSNP | Ensembl ].
VAR_007256
Natural variant1551P → L in MLD; juvenile-onset. Ref.55
Corresponds to variant rs74315464 [ dbSNP | Ensembl ].
VAR_054177
Natural variant1551P → R in MLD.
Corresponds to variant rs74315464 [ dbSNP | Ensembl ].
VAR_007257
Natural variant1561C → R in MLD; adult type; enzyme activity reduced to 50% of wild-type enzyme. Ref.57
Corresponds to variant rs199476348 [ dbSNP | Ensembl ].
VAR_054178
Natural variant1671P → R in MLD.
Corresponds to variant rs74315465 [ dbSNP | Ensembl ].
VAR_007258
Natural variant1691D → N in MLD.
Corresponds to variant rs74315466 [ dbSNP | Ensembl ].
VAR_007259
Natural variant1721C → Y in MLD; juvenile-onset. Ref.32
Corresponds to variant rs199476381 [ dbSNP | Ensembl ].
VAR_007260
Natural variant1791I → S in MLD; mild. Ref.38 Ref.46 Ref.57 Ref.60 Ref.62
Corresponds to variant rs74315457 [ dbSNP | Ensembl ].
VAR_007261
Natural variant1811L → Q in MLD; infantile form. Ref.55
Corresponds to variant rs199476378 [ dbSNP | Ensembl ].
VAR_054179
Natural variant1901Q → H in MLD; no enzyme residual activity. Ref.30
Corresponds to variant rs199476372 [ dbSNP | Ensembl ].
VAR_054180
Natural variant1911P → T in MLD; juvenile-onset. Ref.47
Corresponds to variant rs199476374 [ dbSNP | Ensembl ].
VAR_054181
Natural variant1931W → C. Ref.6 Ref.21 Ref.43 Ref.45 Ref.51 Ref.57
Corresponds to variant rs6151415 [ dbSNP | Ensembl ].
VAR_007262
Natural variant2011Y → C in MLD; juvenile-onset; results in higly reduced enzyme activity and stability; the mutant enzyme is kept in a prelysosomal compartment. Ref.32 Ref.48 Ref.60
Corresponds to variant rs199476345 [ dbSNP | Ensembl ].
VAR_007263
Natural variant2121A → P in MLD; loss of enzymatic activity. Ref.60 Ref.61
Corresponds to variant rs199476341 [ dbSNP | Ensembl ].
VAR_054182
Natural variant2121A → V in MLD. Ref.27 Ref.45 Ref.55
Corresponds to variant rs74315467 [ dbSNP | Ensembl ].
VAR_007264
Natural variant2171R → H in MLD; enzyme activity reduced to 15.6% of wild-type enzyme. Ref.60
Corresponds to variant rs148403406 [ dbSNP | Ensembl ].
VAR_054183
Natural variant2191F → V in MLD; enzyme activity reduced to less than 1% of normal activity. Ref.59
Corresponds to variant rs199476383 [ dbSNP | Ensembl ].
VAR_054184
Natural variant2241A → V in MLD. Ref.27
Corresponds to variant rs74315468 [ dbSNP | Ensembl ].
VAR_007265
Natural variant2271H → Y in MLD; late-infantile form. Ref.45
Corresponds to variant rs199476354 [ dbSNP | Ensembl ].
VAR_054185
Natural variant2311P → T in MLD.
Corresponds to variant rs74315469 [ dbSNP | Ensembl ].
VAR_007266
Natural variant2441R → C in MLD; juvenile-onset.
Corresponds to variant rs74315470 [ dbSNP | Ensembl ].
VAR_007267
Natural variant2441R → H in MLD; infantile-onset. Ref.36
Corresponds to variant rs199476366 [ dbSNP | Ensembl ].
VAR_007268
Natural variant2451G → R in MLD; severe. Ref.24
Corresponds to variant rs74315471 [ dbSNP | Ensembl ].
VAR_007269
Natural variant2471F → S in MLD. Ref.56 Ref.62
Corresponds to variant rs199476384 [ dbSNP | Ensembl ].
VAR_054186
Natural variant2501S → Y in MLD; infantile-onset. Ref.36
Corresponds to variant rs199476367 [ dbSNP | Ensembl ].
VAR_007270
Natural variant2531E → K in MLD; late-infantile. Ref.52 Ref.60
Corresponds to variant rs74315483 [ dbSNP | Ensembl ].
VAR_054187
Natural variant2551D → 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. Ref.45 Ref.48
Corresponds to variant rs80338819 [ dbSNP | Ensembl ].
VAR_054188
Natural variant2741T → M in MLD; severe; 35% of normal activity. Ref.28 Ref.30 Ref.34
Corresponds to variant rs74315472 [ dbSNP | Ensembl ].
VAR_007271
Natural variant2811D → Y in MLD. Ref.46
Corresponds to variant rs199476386 [ dbSNP | Ensembl ].
VAR_054189
Natural variant2821N → S in MLD; enzyme activity reduced to 0.6% of wild-type enzyme. Ref.60
Corresponds to variant rs199476342 [ dbSNP | Ensembl ].
VAR_054190
Natural variant2861T → P in MLD; adult type. Ref.49
Corresponds to variant rs28940894 [ dbSNP | Ensembl ].
VAR_054191
Natural variant2881R → C in MLD. Ref.62
Corresponds to variant rs74315473 [ dbSNP | Ensembl ].
VAR_007272
Natural variant2881R → H in MLD; adult form. Ref.45
Corresponds to variant rs199476355 [ dbSNP | Ensembl ].
VAR_054192
Natural variant2931G → D in MLD; late-onset. Ref.58
Corresponds to variant rs199476387 [ dbSNP | Ensembl ].
VAR_054193
Natural variant2931G → S in MLD; adult type; causes a severe reduction of enzyme activity. Ref.57
Corresponds to variant rs199476349 [ dbSNP | Ensembl ].
VAR_054194
Natural variant2941C → Y in MLD; juvenile-onset; causes a severe reduction of enzyme activity. Ref.57
Corresponds to variant rs199476347 [ dbSNP | Ensembl ].
VAR_054195
Natural variant2951S → Y in MLD; severe. Ref.27
Corresponds to variant rs74315474 [ dbSNP | Ensembl ].
VAR_007273
Natural variant2981L → S in MLD; late-infantile form; complete loss of enzyme activity. Ref.42
Corresponds to variant rs199476389 [ dbSNP | Ensembl ].
VAR_054196
Natural variant3001C → 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. Ref.44 Ref.53 Ref.54
Corresponds to variant rs74315484 [ dbSNP | Ensembl ].
VAR_008132
Natural variant3021K → N in MLD; enzyme activity reduced to 2.8% of wild-type enzyme. Ref.60
Corresponds to variant rs199476343 [ dbSNP | Ensembl ].
VAR_054197
Natural variant3041T → M in MLD; loss of enzymatic activity. Ref.61
Corresponds to variant rs199476359 [ dbSNP | Ensembl ].
VAR_067416
Natural variant3061Y → H in MLD; juvenile-onset. Ref.55
Corresponds to variant rs199476379 [ dbSNP | Ensembl ].
VAR_054198
Natural variant3071E → K in MLD; loss of enzymatic activity. Ref.61
Corresponds to variant rs199476360 [ dbSNP | Ensembl ].
VAR_067417
Natural variant3081G → D in MLD; late-infantile form. Ref.45
Corresponds to variant rs199476356 [ dbSNP | Ensembl ].
VAR_054199
Natural variant3081G → V in MLD; late-infantile form; no enzyme residual activity. Ref.33
Corresponds to variant rs199476356 [ dbSNP | Ensembl ].
VAR_054200
Natural variant3091G → S in MLD; severe; 13% of normal activity. Ref.23 Ref.57
Corresponds to variant rs74315459 [ dbSNP | Ensembl ].
VAR_007274
Natural variant3111R → Q in MLD; juvenile-onset. Ref.32
Corresponds to variant rs199476382 [ dbSNP | Ensembl ].
VAR_007275
Natural variant3121E → D in MLD; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme. Ref.48
Corresponds to variant rs199476390 [ dbSNP | Ensembl ].
VAR_054201
Natural variant3141A → T in MLD; infantile-onset. Ref.36
Corresponds to variant rs199476368 [ dbSNP | Ensembl ].
VAR_007276
Natural variant3251G → S in MLD; juvenile-onset. Ref.55
Corresponds to variant rs148092995 [ dbSNP | Ensembl ].
VAR_054202
Natural variant3271T → I in MLD; late-infantile form. Ref.45
VAR_054203
Natural variant3351D → V in MLD; late-infantile-onset; loss of enzymatic activity. Ref.32 Ref.34 Ref.47 Ref.55 Ref.62
Corresponds to variant rs74315475 [ dbSNP | Ensembl ].
VAR_007277
Natural variant3501N → 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. Ref.6 Ref.18 Ref.45 Ref.52 Ref.58
Corresponds to variant rs2071421 [ dbSNP | Ensembl ].
VAR_007278
Natural variant3561F → V. Ref.6
Corresponds to variant rs6151422 [ dbSNP | Ensembl ].
VAR_018838
Natural variant3671K → N in MLD. Ref.36
Corresponds to variant rs199476369 [ dbSNP | Ensembl ].
VAR_007279
Natural variant3701R → Q in MLD; mild.
Corresponds to variant rs74315477 [ dbSNP | Ensembl ].
VAR_007280
Natural variant3701R → W in MLD; severe; no enzyme residual activity. Ref.30 Ref.60
Corresponds to variant rs74315476 [ dbSNP | Ensembl ].
VAR_007281
Natural variant3761Y → N in MLD; enzyme activity reduced to 4.7% of wild-type enzyme. Ref.60
Corresponds to variant rs199476344 [ dbSNP | Ensembl ].
VAR_054204
Natural variant3771P → L in MLD; severe. Ref.45
Corresponds to variant rs74315478 [ dbSNP | Ensembl ].
VAR_007282
Natural variant3811D → E in MLD; early-infantile form. Ref.56
Corresponds to variant rs6151425 [ dbSNP | Ensembl ].
VAR_054205
Natural variant3821E → K in MLD; intermediate. Ref.62
Corresponds to variant rs74315479 [ dbSNP | Ensembl ].
VAR_007283
Natural variant3841R → C in MLD. Ref.36
Corresponds to variant rs199476370 [ dbSNP | Ensembl ].
VAR_007284
Natural variant3901R → Q in MLD; juvenile-onset. Ref.41 Ref.62
Corresponds to variant rs199476391 [ dbSNP | Ensembl ].
VAR_007285
Natural variant3901R → W in MLD; late-infantile and juvenile-onset. Ref.32 Ref.60 Ref.62
Corresponds to variant rs74315480 [ dbSNP | Ensembl ].
VAR_007286
Natural variant3911T → S. Ref.5 Ref.6 Ref.8 Ref.21 Ref.43 Ref.45 Ref.49 Ref.51 Ref.52 Ref.57
Corresponds to variant rs743616 [ dbSNP | Ensembl ].
VAR_007287
Natural variant3971H → Y in MLD; adult-onset. Ref.41 Ref.47 Ref.62
Corresponds to variant rs199476376 [ dbSNP | Ensembl ].
VAR_007288
Natural variant3981Missing in MLD.
VAR_007289
Natural variant406 – 4083Missing in MLD; late-infantile-onset.
VAR_007290
Natural variant4061S → G in MLD; loss of enzymatic activity. Ref.61
Corresponds to variant rs199476361 [ dbSNP | Ensembl ].
VAR_067418
Natural variant4081T → I in MLD; adult type. Ref.51
Corresponds to variant rs28940895 [ dbSNP | Ensembl ].
VAR_054206
Natural variant4091T → I in MLD; mild. Ref.29 Ref.63
Corresponds to variant rs74315481 [ dbSNP | Ensembl ].
VAR_054207
Natural variant4251P → 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. Ref.44 Ref.53 Ref.54
Corresponds to variant rs74315485 [ dbSNP | Ensembl ].
VAR_008133
Natural variant4261P → L in MLD; juvenile/adult-onset; mild; common mutation. Ref.21 Ref.25 Ref.47 Ref.52 Ref.55 Ref.56 Ref.57 Ref.62
Corresponds to variant rs28940893 [ dbSNP | Ensembl ].
VAR_007291
Natural variant4281L → P in MLD; late-infantile form. Ref.35 Ref.60
Corresponds to variant rs199476392 [ dbSNP | Ensembl ].
VAR_054208
Natural variant4291Y → S in MLD; adult-onset. Ref.55
Corresponds to variant rs199476380 [ dbSNP | Ensembl ].
VAR_054209
Natural variant4401N → S. Ref.6
Corresponds to variant rs6151427 [ dbSNP | Ensembl ].
VAR_018839
Natural variant4641A → V. Ref.43
VAR_007292
Natural variant4691A → G in MLD; early-infantile form. Ref.56
Corresponds to variant rs199476385 [ dbSNP | Ensembl ].
VAR_054210
Natural variant4891C → G in MLD; late-onset. Ref.58
Corresponds to variant rs199476388 [ dbSNP | Ensembl ].
VAR_054211
Natural variant4961R → H. Ref.6 Ref.36 Ref.40
Corresponds to variant rs6151428 [ dbSNP | Ensembl ].
VAR_007293

Experimental info

Mutagenesis691C → A: Abolishes enzyme activity. Ref.14
Mutagenesis691C → S: Strongly decreases enzyme activity. Ref.14
Sequence conflict2901S → P in AK098659. Ref.5

Secondary structure

......................................................................................... 507
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1991. Version 3.
Checksum: 3DDBE1378B4176A6

FASTA50753,588
        10         20         30         40         50         60 
MGAPRSLLLA LAAGLAVARP PNIVLIFADD LGYGDLGCYG HPSSTTPNLD QLAAGGLRFT 

        70         80         90        100        110        120 
DFYVPVSLCT PSRAALLTGR LPVRMGMYPG VLVPSSRGGL PLEEVTVAEV LAARGYLTGM 

       130        140        150        160        170        180 
AGKWHLGVGP EGAFLPPHQG FHRFLGIPYS HDQGPCQNLT CFPPATPCDG GCDQGLVPIP 

       190        200        210        220        230        240 
LLANLSVEAQ PPWLPGLEAR YMAFAHDLMA DAQRQDRPFF LYYASHHTHY PQFSGQSFAE 

       250        260        270        280        290        300 
RSGRGPFGDS LMELDAAVGT LMTAIGDLGL LEETLVIFTA DNGPETMRMS RGGCSGLLRC 

       310        320        330        340        350        360 
GKGTTYEGGV REPALAFWPG HIAPGVTHEL ASSLDLLPTL AALAGAPLPN VTLDGFDLSP 

       370        380        390        400        410        420 
LLLGTGKSPR QSLFFYPSYP DEVRGVFAVR TGKYKAHFFT QGSAHSDTTA DPACHASSSL 

       430        440        450        460        470        480 
TAHEPPLLYD LSKDPGENYN LLGGVAGATP EVLQALKQLQ LLKAQLDAAV TFGPSQVARG 

       490        500 
EDPALQICCH PGCTPRPACC HCPDPHA 

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Isoform 2 [UniParc].

Checksum: D67E0EE072BEC7BB
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FASTA42344,881

References

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[1]"Cloning and expression of human arylsulfatase A."
Stein C., Gieselmann V., Kreysing J., Schmidt B., Pohlmann R., Waheed A., Meyer H.E., O'Brien J.S., von Figura K.
J. Biol. Chem. 264:1252-1259(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Structure of the arylsulfatase A gene."
Kreysing J., von Figura K., Gieselmann V.
Eur. J. Biochem. 191:627-631(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Characterization of the arylsulfatase I (ARSI) gene preferentially expressed in the human retinal pigment epithelium cell line ARPE-19."
Oshikawa M., Usami R., Kato S.
Mol. Vis. 15:482-494(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT SER-391.
Tissue: Testis.
[6]NIEHS SNPs program
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-82; CYS-193; SER-350; VAL-356; SER-391; SER-440 AND HIS-496.
[7]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-391.
Tissue: B-cell.
[9]"Proteolytic processing of human lysosomal arylsulfatase A."
Fujii T., Kobayashi T., Honke K., Gasa S., Ishikawa M., Shimizu T., Makita A.
Biochim. Biophys. Acta 1122:93-98(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-33 AND 434-479, SUBUNIT.
[10]"A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency."
Schmidt B., Selmer T., Ingendoh A., von Figura K.
Cell 82:271-278(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, OXOALANINE AT CYS-69, ABSENCE OF OXOALANINE IN MSD.
[11]"Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency."
Cosma M.P., Pepe S., Parenti G., Settembre C., Annunziata I., Wade-Martins R., Domenico C.D., Natale P.D., Mankad A., Cox B., Uziel G., Mancini G.M., Zammarchi E., Donati M.A., Kleijer W.J., Filocamo M., Carrozzo R., Carella M., Ballabio A.
Hum. Mutat. 23:576-581(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MSD.
[12]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-158 AND ASN-350.
Tissue: Liver.
[13]"Crystal structure of human arylsulfatase A: the aldehyde function and the metal ion at the active site suggest a novel mechanism for sulfate ester hydrolysis."
Lukatela G., Krauss N., Theis K., Selmer T., Gieselmann V., von Figura K., Saenger W.
Biochemistry 37:3654-3664(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), OLIGOMERIZATION.
[14]"Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis."
von Buelow R., Schmidt B., Dierks T., von Figura K., Uson I.
J. Mol. Biol. 305:269-277(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS), MUTAGENESIS OF CYS-69.
[15]"Crystal structure of a covalent intermediate of endogenous human arylsulfatase A."
Chruszcz M., Laidler P., Monkiewicz M., Ortlund E., Lebioda L., Lewinski K.
J. Inorg. Biochem. 96:386-392(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 19-507, SUBUNIT, GLYCOSYLATION AT ASN-158 AND ASN-184, ACTIVE SITE, ENZYME REGULATION, CALCIUM-BINDING, COFACTOR.
[16]"A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme."
Roeser D., Preusser-Kunze A., Schmidt B., Gasow K., Wittmann J.G., Dierks T., von Figura K., Rudolph M.G.
Proc. Natl. Acad. Sci. U.S.A. 103:81-86(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 69-73 IN COMPLEX WITH SUMF1.
[17]"Molecular genetics of metachromatic leukodystrophy."
Gieselmann V., Zlotogora J., Harris A., Wenger D.A., Morris C.P.
Hum. Mutat. 4:233-242(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON MLD VARIANTS.
[18]"Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site."
Gieselmann V., Polten A., Kreysing J., von Figura K.
Proc. Natl. Acad. Sci. U.S.A. 86:9436-9440(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-350, ASSOCIATION WITH ARYLSULFATASE A PSEUDODEFICIENCY.
[19]"Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy."
Kondo R., Wakamatsu N., Yoshino H., Fukuhara N., Miyatake T., Tsuji S.
Am. J. Hum. Genet. 48:971-978(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD ASP-99.
[20]"Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy."
Gieselmann V., Fluharty A.L., Toennesen T., von Figura K.
Am. J. Hum. Genet. 49:407-413(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD PHE-96.
[21]"Molecular basis of different forms of metachromatic leukodystrophy."
Polten A., Fluharty A.L., Fluharty C.B., Kappler J., von Figura K., Gieselmann V.
N. Engl. J. Med. 324:18-22(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD LEU-426, VARIANTS CYS-193 AND SER-391.
[22]"Late-onset metachromatic leukodystrophy: molecular pathology in two siblings."
Kappler J., von Figura K., Gieselmann V.
Ann. Neurol. 31:256-261(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD GLN-84.
[23]"High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy."
Kreysing J., Bohne W., Bosenberg C., Marchesini S., Turpin J.C., Baumann N., von Figura K., Gieselmann V.
Am. J. Hum. Genet. 53:339-346(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD SER-309.
[24]"Mutations in the arylsulfatase A gene of Japanese patients with metachromatic leukodystrophy."
Hasegawa Y., Kawame H., Eto Y.
DNA Cell Biol. 12:493-498(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD ARG-245.
[25]"Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain."
Barth M.L., Fensom A., Harris A.
Hum. Genet. 91:73-77(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD LEU-426.
[26]"An adult-type metachromatic leukodystrophy caused by substitution of serine for glycine-122 in arylsulfatase A."
Honke K., Kobayashi T., Fujii T., Gasa S., Xu M., Takamaru Y., Kondo R., Tsuji S., Makita A.
Hum. Genet. 92:451-456(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD SER-122.
[27]"Missense mutations in the arylsulphatase A genes of metachromatic leukodystrophy patients."
Barth M.L., Fensom A., Harris A.
Hum. Mol. Genet. 2:2117-2121(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD VAL-212; VAL-224 AND TYR-295.
[28]"An arylsulfatase A (ARSA) missense mutation (T274M) causing late-infantile metachromatic leukodystrophy."
Harvey J.S., Nelson P.V., Carey W.F., Robertson E.F., Morris C.P.
Hum. Mutat. 2:261-267(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD MET-274.
[29]"Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing."
Hasegawa Y., Kawame H., Ida H., Ohashi T., Eto Y.
Hum. Genet. 93:415-420(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD ILE-409.
[30]"Multiple mutations are responsible for the high frequency of metachromatic leukodystrophy in a small geographic area."
Heinisch U., Zlotogora J., Kafert S., Gieselmann V.
Am. J. Hum. Genet. 56:51-57(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASP-86; LEU-96; HIS-190; MET-274 AND TRP-370, CHARACTERIZATION OF VARIANTS MLD ASP-86; LEU-96; HIS-190; MET-274 AND TRP-370.
[31]"A missense mutation P136L in the arylsulfatase A gene causes instability and loss of activity of the mutant enzyme."
Kafert S., Heinisch U., Zlotogora J., Gieselmann V.
Hum. Genet. 95:201-204(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD LEU-136.
[32]"Identification of seven novel mutations associated with metachromatic leukodystrophy."
Barth M.L., Fensom A., Harris A.
Hum. Mutat. 6:170-176(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD LEU-82; TYR-172; CYS-201; GLN-311; VAL-335 AND TRP-390.
[33]"Two novel mutations in a Japanese patient with the late-infantile form of metachromatic leukodystrophy."
Tsuda T., Hasegawa Y., Eto Y.
Brain Dev. 18:400-403(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD HIS-153 AND VAL-308, CHARACTERIZATION OF VARIANTS MLD HIS-153 AND VAL-308.
[34]"Characterization of two arylsulfatase A missense mutations D335V and T274M causing late infantile metachromatic leukodystrophy."
Hess B., Kafert S., Heinisch U., Wenger D.A., Zlotogora J., Gieselmann V.
Hum. Mutat. 7:311-317(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS MET-274 AND VAL-335.
[35]"A T > C transition causing a Leu > Pro substitution in a conserved region of the arylsulfatase A gene in a late infantile metachromatic leukodystrophy patient."
Regis S., Filocamo M., Stroppiano M., Corsolini F., Gatti R.
Clin. Genet. 52:65-67(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD PRO-428.
[36]"Metachromatic leukodystrophy: identification of the first deletion in exon 1 and of nine novel point mutations in the arylsulfatase A gene."
Draghia R., Letourneur F., Drugan C., Manicom J., Blanchot C., Kahn A., Poenaru L., Caillaud C.
Hum. Mutat. 9:234-242(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASN-95; ARG-119; TYR-152; HIS-244; TYR-250; THR-314; ASN-367 AND CYS-384, VARIANT HIS-496.
[37]"A 9-bp deletion (2320del9) on the background of the arylsulfatase A pseudodeficiency allele in a metachromatic leukodystrophy patient and in a patient with nonprogressive neurological symptoms."
Regis S., Filocamo M., Stroppiano M., Corsolini F., Caroli F., Gatti R.
Hum. Genet. 102:50-53(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD 406-SER--THR-408 DEL.
[38]"Molecular genetic characterization of two metachromatic leukodystrophy patients who carry the T799G mutation and show different phenotypes; description of a novel null-type mutation."
Gomez-Lira M., Perusi C., Mottes M., Pignatti P.F., Manfredi M., Rizzuto N., Salviati A.
Hum. Genet. 102:459-463(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD PRO-135 AND SER-179.
[39]Erratum
Gomez-Lira M., Perusi C., Mottes M., Pignatti P.F., Manfredi M., Rizzuto N., Salviati A.
Hum. Genet. 102:602-602(1998)
[40]"The R496H mutation of arylsulfatase A does not cause metachromatic leukodystrophy."
Ricketts M.H., Poretz R.D., Manowitz P.
Hum. Mutat. 12:238-239(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-496.
[41]"Two novel mutations in the arylsulfatase A gene associated with juvenile (R390Q) and adult onset (H397Y) metachromatic leukodystrophy."
Coulter-Mackie M.B., Gagnier L.
Hum. Mutat. Suppl. 1:S254-S256(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD GLN-390 AND TYR-397.
[42]"Prevalence of arylsulphatase A mutations in 11 Japanese patients with metachromatic leukodystrophy: identification of two novel mutations."
Kurosawa K., Ida H., Eto Y.
J. Inherit. Metab. Dis. 21:781-782(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD SER-298, CHARACTERIZATION OF VARIANT MLD SER-298.
[43]"Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity."
Berger J., Gmach M., Mayr U., Molzer B., Bernheimer H.
Hum. Mutat. 13:61-68(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRO-76; CYS-193; SER-391 AND VAL-464.
[44]"Metachromatic leucodystrophy in Portugal-finding of four new molecular lesions: C300F, P425T, g.1190-1191insC, and g.2408delC."
Marcao A., Amaral O., Pinto E., Pinto R., Sa Miranda M.C.
Hum. Mutat. 13:337-338(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD PHE-300 AND THR-425.
[45]"Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients."
Gort L., Coll M.J., Chabas A.
Hum. Mutat. 14:240-248(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD SER-32; PRO-68; TRP-84; ALA-94; VAL-99; SER-136; VAL-212; TYR-227; HIS-255; HIS-288; ASP-308; ILE-327 AND LEU-377, VARIANTS CYS-193; SER-350 AND SER-391.
[46]"Metachromatic leucodystrophy: a newly identified mutation in arylsulphatase A, D281Y, found as a compound heterozygote with I179L in an adult onset case."
Halsall D.J., Halligan E.P., Elsey T.S., Cox T.M.
Hum. Mutat. 14:447-447(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD SER-179 AND TYR-281.
[47]"Metachromatic leukodystrophy: subtype genotype/phenotype correlations and identification of novel missense mutations (P148L and P191T) causing the juvenile-onset disease."
Qu Y., Shapira E., Desnick R.J.
Mol. Genet. Metab. 67:206-212(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD LEU-148; THR-191; VAL-335; TYR-397 AND LEU-426.
[48]"Characterization of four arylsulfatase A missense mutations G86D, Y201C, D255H, and E312D causing metachromatic leukodystrophy."
Hermann S., Schestag F., Polten A., Kafert S., Penzien J., Zlotogora J., Baumann N., Gieselmann V.
Am. J. Med. Genet. 91:68-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASP-86; CYS-201; HIS-255 AND ASP-312, CHARACTERIZATION OF VARIANTS MLD ASP-86; CYS-201; HIS-255 AND ASP-312.
[49]"Adult-onset MLD: a gene mutation with isolated polyneuropathy."
Felice K.J., Gomez Lira M., Natowicz M., Grunnet M.L., Tsongalis G.J., Sima A.A.F., Kaplan R.F.
Neurology 55:1036-1039(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD PRO-286, VARIANT SER-391.
[50]"Variable onset of metachromatic leukodystrophy in a Vietnamese family."
Arbour L.T., Silver K., Hechtman P., Treacy E.P., Coulter-Mackie M.B.
Pediatr. Neurol. 23:173-176(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD GLY-143, CHARACTERIZATION OF VARIANT MLD GLY-143.
[51]"Late-onset metachromatic leukodystrophy clinically presenting as isolated peripheral neuropathy: compound heterozygosity for the IVS2+1G-->A mutation and a newly identified missense mutation (Thr408Ile) in a Spanish family."
Comabella M., Waye J.S., Raguer N., Eng B., Dominguez C., Navarro C., Borras C., Krivit W., Montalban X.
Ann. Neurol. 50:108-112(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD ILE-408, VARIANTS CYS-193 AND SER-391.
[52]"Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severity."
Regis S., Corsolini F., Stroppiano M., Cusano R., Filocamo M.
Hum. Genet. 110:351-355(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD LYS-253, VARIANTS SER-350; SER-391 AND LEU-426.
[53]"Biochemical characterization of two (C300F, P425T) arylsulfatase A missense mutations."
Marcao A., Simonis H., Schestag F., Sa Miranda M.C., Gieselmann V.
Am. J. Med. Genet. A 116:238-242(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS MLD PHE-300 AND THR-425.
[54]"Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T."
Marcao A., Azevedo J.E., Gieselmann V., Sa Miranda M.C.
Biochem. Biophys. Res. Commun. 306:293-297(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS MLD PHE-300 AND THR-425.
[55]"Identification of nine novel arylsulfatase A (ARSA) gene mutations in patients with metachromatic leukodystrophy (MLD)."
Eng B., Nakamura L.N., O'Reilly N., Schokman N., Nowaczyk M.M.J., Krivit W., Waye J.S.
Hum. Mutat. 22:418-419(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD LEU-155; GLN-181; VAL-212; HIS-306; SER-325; VAL-335; LEU-426 AND SER-429.
[56]"Novel mutations in arylsulfatase A gene in three Ukrainian families with metachromatic leukodystrophy."
Olkhovich N.V., Takamura N., Pichkur N.A., Gorovenko N.G., Aoyagi K., Yamashita S.
Mol. Genet. Metab. 80:360-363(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD SER-136; SER-247; GLU-381 LEU-426 AND GLY-469.
[57]"Novel mutations associated with metachromatic leukodystrophy: phenotype and expression studies in nine Czech and Slovak patients."
Berna L., Gieselmann V., Poupetova H., Hrebicek M., Elleder M., Ledvinova J.
Am. J. Med. Genet. A 129:277-281(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASN-29; ARG-156; SER-179; SER-293; TYR-294; SER-309 AND LEU-426, VARIANTS CYS-193 AND SER-391, CHARACTERIZATION OF VARIANTS MLD ASN-29; ARG-156; SER-293 AND TYR-294.
[58]"Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene."
Gallo S., Randi D., Bertelli M., Salviati A., Pandolfo M.
J. Neurol. Neurosurg. Psych. 75:655-657(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASP-293 AND GLY-489, VARIANT SER-350.
[59]"Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene."
Marcao A.M., Wiest R., Schindler K., Wiesmann U., Weis J., Schroth G., Miranda M.C.S., Sturzenegger M., Gieselmann V.
Arch. Neurol. 62:309-313(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD VAL-219, CHARACTERIZATION OF VARIANT MLD VAL-219.
[60]"Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles."
Grossi S., Regis S., Rosano C., Corsolini F., Uziel G., Sessa M., Di Rocco M., Parenti G., Deodato F., Leuzzi V., Biancheri R., Filocamo M.
Hum. Mutat. 29:E220-E230(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASP-18; HIS-30; GLN-84; PRO-137 DEL; ASP-154; SER-179; CYS-201; PRO-212; HIS-217; LYS-253; SER-282; ASN-302; TRP-370; ASN-376; TRP-390 AND PRO-428, CHARACTERIZATION OF VARIANTS MLD ASP-18; HIS-30; PRO-212; HIS-217; SER-282; ASN-302; TRP-370 AND ASN-376.
[61]"Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy."
Cesani M., Capotondo A., Plati T., Sergi L.S., Fumagalli F., Roncarolo M.G., Naldini L., Comi G., Sessa M., Biffi A.
Hum. Mutat. 30:E936-E945(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD PRO-52; ASP-138; PRO-212; MET-304; LYS-307 AND GLY-406, CHARACTERIZATION OF VARIANTS MLD PRO-52; ASP-138; PRO-212; MET-304; LYS-307 AND GLY-406.
[62]"Molecular bases of metachromatic leukodystrophy in Polish patients."
Lugowska A., Ploski R., Wlodarski P., Tylki-Szymanska A.
J. Hum. Genet. 55:394-396(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD SER-179; SER-247; CYS-288; VAL-335; LYS-382; GLN-390; TRP-390; TYR-397 AND LEU-426.
[63]"Adult-type metachromatic leukodystrophy with compound heterozygous ARSA mutations: a case report and phenotypic comparison with a previously reported case."
Hayashi T., Nakamura M., Ichiba M., Matsuda M., Kato M., Shiokawa N., Shimo H., Tomiyasu A., Mori S., Tomiyasu Y., Ishizuka T., Inamori Y., Okamoto Y., Umehara F., Arimura K., Nakabeppu Y., Sano A.
Psychiatry Clin. Neurosci. 65:105-108(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLD ASP-99 AND ILE-409.
+Additional computationally mapped references.

Web resources

GeneReviews
NIEHS-SNPs
Wikipedia

Arylsulfatase A entry

Arylsulfatase A (ARSA)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52151 mRNA. Translation: CAA36399.1.
X52150 Genomic DNA. Translation: CAA36398.1.
AB448736 mRNA. Translation: BAH11167.1. Different initiation.
CR456383 mRNA. Translation: CAG30269.1.
AK098659 mRNA. No translation available.
AK315011 mRNA. Translation: BAG37503.1.
AY271820 Genomic DNA. Translation: AAP03431.1.
U62317 Genomic DNA. Translation: AAB03341.1. Different initiation.
BC014210 mRNA. Translation: AAH14210.2.
PIRKJHUAA. S11031.
RefSeqNP_000478.3. NM_000487.5.
NP_001078894.2. NM_001085425.2.
NP_001078895.2. NM_001085426.2.
NP_001078896.2. NM_001085427.2.
NP_001078897.1. NM_001085428.2.
UniGeneHs.731715.
Hs.88251.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP15289.
SMRP15289. Positions 19-504.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106903. 4 interactions.
IntActP15289. 5 interactions.
STRING9606.ENSP00000216124.

Chemistry

ChEMBLCHEMBL2193.
DrugBankDB01141. Micafungin.

PTM databases

UniCarbKBP15289.

Proteomic databases

PaxDbP15289.
PRIDEP15289.

Protocols and materials databases

DNASU410.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216124; ENSP00000216124; ENSG00000100299.
ENST00000356098; ENSP00000348406; ENSG00000100299.
ENST00000395619; ENSP00000378981; ENSG00000100299.
ENST00000395621; ENSP00000378983; ENSG00000100299.
ENST00000453344; ENSP00000412542; ENSG00000100299. [P15289-2]
ENST00000547307; ENSP00000448440; ENSG00000100299. [P15289-1]
ENST00000547805; ENSP00000448932; ENSG00000100299. [P15289-1]
GeneID410.
KEGGhsa:410.
UCSCuc003bmz.5. human. [P15289-1]

Organism-specific databases

CTD410.
GeneCardsGC22M051063.
HGNCHGNC:713. ARSA.
HPACAB025183.
HPA005554.
MIM250100. phenotype.
272200. phenotype.
607574. gene.
neXtProtNX_P15289.
Orphanet309271. Metachromatic leukodystrophy, adult form.
309263. Metachromatic leukodystrophy, juvenile form.
309256. Metachromatic leukodystrophy, late infantile form.
751. Pseudoarylsulfatase A deficiency.
PharmGKBPA25005.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3119.
HOGENOMHOG000135352.
HOVERGENHBG004283.
InParanoidP15289.
KOK01134.
OrthoDBEOG7QZG9J.
PhylomeDBP15289.

Enzyme and pathway databases

BRENDA3.1.6.8. 2681.
ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.

Gene expression databases

BgeeP15289.
CleanExHS_ARSA.
GenevestigatorP15289.

Family and domain databases

Gene3D3.40.720.10. 1 hit.
InterProIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR000917. Sulfatase.
IPR024607. Sulfatase_CS.
[Graphical view]
PfamPF00884. Sulfatase. 1 hit.
[Graphical view]
SUPFAMSSF53649. SSF53649. 1 hit.
PROSITEPS00523. SULFATASE_1. 1 hit.
PS00149. SULFATASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP15289.
GeneWikiArylsulfatase_A.
GenomeRNAi410.
NextBio1725.
PMAP-CutDBP15289.
PROP15289.
SOURCESearch...

Entry information

Entry nameARSA_HUMAN
AccessionPrimary (citable) accession number: P15289
Secondary accession number(s): B2RCA6 expand/collapse secondary AC list , B7XD04, F8WCC8, Q6ICI5, Q96CJ0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 163 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM