P15289 (ARSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	507 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.14
Enzyme regulation	Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine. Ref.14
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.8 Ref.12 Ref.14
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	Defects in ARSA are a cause of leukodystrophy metachromatic (MLD) [MIM:250100]. MLD is a disease due to a lysosomal storage defect. It is 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. Ref.18 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.34 Ref.35 Ref.36 Ref.37 Ref.40 Ref.41 Ref.43 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 Arylsulfatase A activity is defective in 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=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.9 Ref.10
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.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Ichthyosis Leukodystrophy Metachromatic leukodystrophy
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	glycosphingolipid metabolic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular component	lysosomal lumen Traceable author statement. Source: Reactome
Molecular function	arylsulfatase activity Traceable author statement Ref.1. Source: ProtInc calcium ion binding Inferred from direct assay Ref.14. Source: UniProtKB cerebroside-sulfatase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.8

Chain

19 – 507

489

Arylsulfatase A

PRO_0000033417

Chain

19 – 444

426

Arylsulfatase A component B

PRO_0000033418

Chain

448 – 507

60

Arylsulfatase A component C

PRO_0000033419

Sites

Active site

125

1

Ref.14

Metal binding

29

1

Calcium

Metal binding

30

1

Calcium

Metal binding

69

1

Calcium; via 3-oxoalanine

Metal binding

281

1

Calcium

Metal binding

282

1

Calcium

Binding site

123

1

Substrate

Binding site

150

1

Substrate

Binding site

229

1

Substrate

Binding site

302

1

Substrate

Amino acid modifications

Modified residue

69

1

3-oxoalanine (Cys)

Glycosylation

158

1

N-linked (GlcNAc...) Ref.11 Ref.14

Glycosylation

184

1

N-linked (GlcNAc...) Ref.14

Glycosylation

350

1

N-linked (GlcNAc...) Ref.11

Disulfide bond

156 ↔ 172

Disulfide bond

161 ↔ 168

Disulfide bond

300 ↔ 414

Disulfide bond

488 ↔ 500

Disulfide bond

489 ↔ 502

Disulfide bond

493 ↔ 499

Natural variations

Natural variant

18

1

A → D in MLD; enzyme activity reduced to 5% of wild-type enzyme. Ref.59

VAR_054164

Natural variant

29

1

D → N in MLD; infantile-onset; causes a severe reduction of enzyme activity. Ref.56

VAR_054165

Natural variant

30

1

D → H in MLD; enzyme activity reduced to 2.4% of wild-type enzyme. Ref.59

VAR_054166

Natural variant

32

1

G → S in MLD; late-infantile form. Ref.44

VAR_054167

Natural variant

52

1

L → P in MLD; loss of enzymatic activity. Ref.60

VAR_067414

Natural variant

68

1

L → P in MLD; late-infantile form. Ref.44

VAR_054168

Natural variant

76

1

L → P. Ref.42

VAR_007243

Natural variant

82

1

P → L in MLD; late-infantile-onset. Ref.5 Ref.31
Corresponds to variant rs6151411 [ dbSNP | Ensembl ].

VAR_007244

Natural variant

84

1

R → Q in MLD; mild. Ref.21 Ref.59
Corresponds to variant rs74315458 [ dbSNP | Ensembl ].

VAR_007245

Natural variant

84

1

R → W in MLD; juvenile form. Ref.44

VAR_054169

Natural variant

86

1

G → 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.29 Ref.47
Corresponds to variant rs74315460 [ dbSNP | Ensembl ].

VAR_007246

Natural variant

94

1

P → A in MLD; adult form. Ref.44

VAR_054170

Natural variant

95

1

S → N in MLD. Ref.35

VAR_007247

Natural variant

96

1

S → F in MLD; severe. Ref.19
Corresponds to variant rs74315456 [ dbSNP | Ensembl ].

VAR_007248

Natural variant

96

1

S → L in MLD; severe; no enzyme residual activity. Ref.29

VAR_007249

Natural variant

99

1

G → D in MLD; adult type. Ref.18 Ref.62
Corresponds to variant rs74315455 [ dbSNP | Ensembl ].

VAR_007250

Natural variant

99

1

G → V in MLD; late-infantile form. Ref.44

VAR_054171

Natural variant

119

1

G → R in MLD; juvenile-onset. Ref.35

VAR_007251

Natural variant

122

1

G → S in MLD; adult type; rs74315461. Ref.25

VAR_007252

Natural variant

135

1

L → P in MLD. Ref.37
Corresponds to variant rs121434215 [ dbSNP | Ensembl ].

VAR_007253

Natural variant

136

1

P → L in MLD; severe late-infantile type; loss of enzymatic activity. Ref.30
Corresponds to variant rs74315462 [ dbSNP | Ensembl ].

VAR_007254

Natural variant

136

1

P → S in MLD; late-infantile form. Ref.44 Ref.55

VAR_054172

Natural variant

137

1

Missing in MLD. Ref.59

VAR_054173

Natural variant

138

1

H → D in MLD; significantly lower activity than wild-type protein. Ref.60

VAR_067415

Natural variant

143

1

R → G in MLD; juvenile/adult-onset; generates 5% as much activity as the parallel normal control. Ref.49

VAR_054174

Natural variant

148

1

P → L in MLD; juvenile-onset. Ref.46

VAR_054175

Natural variant

152

1

D → Y in MLD. Ref.35

VAR_007255

Natural variant

153

1

Q → H in MLD; late-infantile form; no enzyme residual activity. Ref.32

VAR_054176

Natural variant

154

1

G → D in MLD. Ref.59
Corresponds to variant rs74315463 [ dbSNP | Ensembl ].

VAR_007256

Natural variant

155

1

P → L in MLD; juvenile-onset. Ref.54

VAR_054177

Natural variant

155

1

P → R in MLD.
Corresponds to variant rs74315464 [ dbSNP | Ensembl ].

VAR_007257

Natural variant

156

1

C → R in MLD; adult type; enzyme activity reduced to 50% of wild-type enzyme. Ref.56

VAR_054178

Natural variant

167

1

P → R in MLD.
Corresponds to variant rs74315465 [ dbSNP | Ensembl ].

VAR_007258

Natural variant

169

1

D → N in MLD.
Corresponds to variant rs74315466 [ dbSNP | Ensembl ].

VAR_007259

Natural variant

172

1

C → Y in MLD; juvenile-onset. Ref.31

VAR_007260

Natural variant

179

1

I → S in MLD; mild. Ref.37 Ref.45 Ref.56 Ref.59 Ref.61
Corresponds to variant rs74315457 [ dbSNP | Ensembl ].

VAR_007261

Natural variant

181

1

L → Q in MLD; infantile form. Ref.54

VAR_054179

Natural variant

190

1

Q → H in MLD; no enzyme residual activity. Ref.29

VAR_054180

Natural variant

191

1

P → T in MLD; juvenile-onset. Ref.46

VAR_054181

Natural variant

193

1

W → C. Ref.5 Ref.20 Ref.42 Ref.44 Ref.50 Ref.56
Corresponds to variant rs6151415 [ dbSNP | Ensembl ].

VAR_007262

Natural variant

201

1

Y → C in MLD; juvenile-onset; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme; causes an arrest of the mutant enzyme polypeptide in a prelysosomal compartment. Ref.31 Ref.47 Ref.59

VAR_007263

Natural variant

212

1

A → P in MLD; loss of enzymatic activity. Ref.59 Ref.60

VAR_054182

Natural variant

212

1

A → V in MLD. Ref.26 Ref.44 Ref.54
Corresponds to variant rs74315467 [ dbSNP | Ensembl ].

VAR_007264

Natural variant

217

1

R → H in MLD; enzyme activity reduced to 15.6% of wild-type enzyme. Ref.59
Corresponds to variant rs148403406 [ dbSNP | Ensembl ].

VAR_054183

Natural variant

219

1

F → V in MLD; enzyme activity reduced to less than 1% of normal activity. Ref.58

VAR_054184

Natural variant

224

1

A → V in MLD. Ref.26
Corresponds to variant rs74315468 [ dbSNP | Ensembl ].

VAR_007265

Natural variant

227

1

H → Y in MLD; late-infantile form. Ref.44

VAR_054185

Natural variant

231

1

P → T in MLD.
Corresponds to variant rs74315469 [ dbSNP | Ensembl ].

VAR_007266

Natural variant

244

1

R → C in MLD; juvenile-onset.
Corresponds to variant rs74315470 [ dbSNP | Ensembl ].

VAR_007267

Natural variant

244

1

R → H in MLD; infantile-onset. Ref.35

VAR_007268

Natural variant

245

1

G → R in MLD; severe. Ref.23
Corresponds to variant rs74315471 [ dbSNP | Ensembl ].

VAR_007269

Natural variant

247

1

F → S in MLD. Ref.55 Ref.61

VAR_054186

Natural variant

250

1

S → Y in MLD; infantile-onset. Ref.35

VAR_007270

Natural variant

253

1

E → K in MLD; late-infantile. Ref.51 Ref.59
Corresponds to variant rs74315483 [ dbSNP | Ensembl ].

VAR_054187

Natural variant

255

1

D → 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.44 Ref.47
Corresponds to variant rs80338819 [ dbSNP | Ensembl ].

VAR_054188

Natural variant

274

1

T → M in MLD; severe; 35% of normal activity. Ref.27 Ref.29 Ref.33
Corresponds to variant rs74315472 [ dbSNP | Ensembl ].

VAR_007271

Natural variant

281

1

D → Y in MLD. Ref.45

VAR_054189

Natural variant

282

1

N → S in MLD; enzyme activity reduced to 0.6% of wild-type enzyme. Ref.59

VAR_054190

Natural variant

286

1

T → P in MLD; adult type. Ref.48
Corresponds to variant rs28940894 [ dbSNP | Ensembl ].

VAR_054191

Natural variant

288

1

R → C in MLD. Ref.61
Corresponds to variant rs74315473 [ dbSNP | Ensembl ].

VAR_007272

Natural variant

288

1

R → H in MLD; adult form. Ref.44

VAR_054192

Natural variant

293

1

G → D in MLD; late-onset. Ref.57

VAR_054193

Natural variant

293

1

G → S in MLD; adult type; causes a severe reduction of enzyme activity. Ref.56

VAR_054194

Natural variant

294

1

C → Y in MLD; juvenile-onset; causes a severe reduction of enzyme activity. Ref.56

VAR_054195

Natural variant

295

1

S → Y in MLD; severe. Ref.26
Corresponds to variant rs74315474 [ dbSNP | Ensembl ].

VAR_007273

Natural variant

298

1

L → S in MLD; late-infantile form; complete loss of enzyme activity. Ref.41

VAR_054196

Natural variant

300

1

C → F in MLD; late-infantile-onset; enzyme activity reduced to less than 1%; the mutant protein is unstable; results in more rapid enzyme degradation in lysosomes; addition of the cysteine protease inhibitor leupeptin does not increase the amount of the enzyme activity; strongly interferes with the octamerization process of the enzyme at low pH. Ref.43 Ref.52 Ref.53

VAR_008132

Natural variant

302

1

K → N in MLD; enzyme activity reduced to 2.8% of wild-type enzyme. Ref.59

VAR_054197

Natural variant

304

1

T → M in MLD; loss of enzymatic activity. Ref.60

VAR_067416

Natural variant

306

1

Y → H in MLD; juvenile-onset. Ref.54

VAR_054198

Natural variant

307

1

E → K in MLD; loss of enzymatic activity. Ref.60

VAR_067417

Natural variant

308

1

G → D in MLD; late-infantile form. Ref.44

VAR_054199

Natural variant

308

1

G → V in MLD; late-infantile form; no enzyme residual activity. Ref.32

VAR_054200

Natural variant

309

1

G → S in MLD; severe; 13% of normal activity. Ref.22 Ref.56
Corresponds to variant rs74315459 [ dbSNP | Ensembl ].

VAR_007274

Natural variant

311

1

R → Q in MLD; juvenile-onset. Ref.31

VAR_007275

Natural variant

312

1

E → D in MLD; low amounts of residual enzyme activity; leads to a decreased stability of the mutant enzyme. Ref.47

VAR_054201

Natural variant

314

1

A → T in MLD; infantile-onset. Ref.35

VAR_007276

Natural variant

325

1

G → S in MLD; juvenile-onset. Ref.54
Corresponds to variant rs148092995 [ dbSNP | Ensembl ].

VAR_054202

Natural variant

327

1

T → I in MLD; late-infantile form. Ref.44

VAR_054203

Natural variant

335

1

D → V in MLD; late-infantile-onset; loss of enzymatic activity. Ref.31 Ref.33 Ref.46 Ref.54 Ref.61
Corresponds to variant rs74315475 [ dbSNP | Ensembl ].

VAR_007277

Natural variant

350

1

N → 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.5 Ref.17 Ref.44 Ref.51 Ref.57
Corresponds to variant rs2071421 [ dbSNP | Ensembl ].

VAR_007278

Natural variant

356

1

F → V. Ref.5
Corresponds to variant rs6151422 [ dbSNP | Ensembl ].

VAR_018838

Natural variant

367

1

K → N in MLD. Ref.35

VAR_007279

Natural variant

370

1

R → Q in MLD; mild.
Corresponds to variant rs74315477 [ dbSNP | Ensembl ].

VAR_007280

Natural variant

370

1

R → W in MLD; severe; no enzyme residual activity. Ref.29 Ref.59
Corresponds to variant rs74315476 [ dbSNP | Ensembl ].

VAR_007281

Natural variant

376

1

Y → N in MLD; enzyme activity reduced to 4.7% of wild-type enzyme. Ref.59

VAR_054204

Natural variant

377

1

P → L in MLD; severe. Ref.44
Corresponds to variant rs74315478 [ dbSNP | Ensembl ].

VAR_007282

Natural variant

381

1

D → E in MLD; early-infantile form. Ref.55

VAR_054205

Natural variant

382

1

E → K in MLD; intermediate. Ref.61
Corresponds to variant rs74315479 [ dbSNP | Ensembl ].

VAR_007283

Natural variant

384

1

R → C in MLD. Ref.35

VAR_007284

Natural variant

390

1

R → Q in MLD; juvenile-onset. Ref.40 Ref.61

VAR_007285

Natural variant

390

1

R → W in MLD; late-infantile and juvenile-onset. Ref.31 Ref.59 Ref.61
Corresponds to variant rs74315480 [ dbSNP | Ensembl ].

VAR_007286

Natural variant

391

1

T → S. Ref.5 Ref.7 Ref.20 Ref.42 Ref.44 Ref.48 Ref.50 Ref.51 Ref.56
Corresponds to variant rs743616 [ dbSNP | Ensembl ].

VAR_007287

Natural variant

397

1

H → Y in MLD; adult-onset. Ref.40 Ref.46 Ref.61

VAR_007288

Natural variant

398

1

Missing in MLD.

VAR_007289

Natural variant

406 – 408

3

Missing in MLD; late-infantile-onset.

VAR_007290

Natural variant

406

1

S → G in MLD; loss of enzymatic activity. Ref.60

VAR_067418

Natural variant

408

1

T → I in MLD; adult type. Ref.50
Corresponds to variant rs28940895 [ dbSNP | Ensembl ].

VAR_054206

Natural variant

409

1

T → I in MLD; mild. Ref.28 Ref.62
Corresponds to variant rs74315481 [ dbSNP | Ensembl ].

VAR_054207

Natural variant

425

1

P → 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.43 Ref.52 Ref.53
Corresponds to variant rs74315485 [ dbSNP | Ensembl ].

VAR_008133

Natural variant

426

1

P → L in MLD; juvenile/adult-onset; mild; common mutation. Ref.20 Ref.24 Ref.46 Ref.51 Ref.54 Ref.55 Ref.56 Ref.61
Corresponds to variant rs28940893 [ dbSNP | Ensembl ].

VAR_007291

Natural variant

428

1

L → P in MLD; late-infantile form. Ref.34 Ref.59

VAR_054208

Natural variant

429

1

Y → S in MLD; adult-onset. Ref.54

VAR_054209

Natural variant

440

1

N → S. Ref.5
Corresponds to variant rs6151427 [ dbSNP | Ensembl ].

VAR_018839

Natural variant

464

1

A → V. Ref.42

VAR_007292

Natural variant

469

1

A → G in MLD; early-infantile form. Ref.55

VAR_054210

Natural variant

489

1

C → G in MLD; late-onset. Ref.57

VAR_054211

Natural variant

496

1

R → H. Ref.5 Ref.35 Ref.39
Corresponds to variant rs6151428 [ dbSNP | Ensembl ].

VAR_007293

Experimental info

Mutagenesis

69

1

C → A: Abolishes enzyme activity. Ref.13

Mutagenesis

69

1

C → S: Strongly decreases enzyme activity. Ref.13

Secondary structure

1

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507

Helix Strand Turn

Details...

Beta strand

22 – 30

9

Helix

37 – 39

3

Helix

47 – 54

8

Beta strand

56 – 63

8

Beta strand

65 – 68

4

Helix

69 – 78

10

Helix

82 – 85

4

Helix

107 – 112

6

Turn

113 – 115

3

Beta strand

117 – 122

6

Helix

130 – 132

3

Helix

136 – 139

4

Beta strand

142 – 146

5

Beta strand

153 – 155

3

Beta strand

159 – 162

4

Turn

163 – 165

3

Beta strand

181 – 183

3

Beta strand

186 – 191

6

Helix

194 – 196

3

Helix

197 – 214

18

Beta strand

219 – 224

6

Beta strand

229 – 231

3

Turn

236 – 241

6

Beta strand

242 – 244

3

Helix

245 – 267

23

Helix

271 – 273

3

Beta strand

274 – 282

9

Helix

286 – 291

6

Beta strand

304 – 306

3

Helix

307 – 310

4

Beta strand

315 – 317

3

Turn

319 – 321

3

Beta strand

324 – 327

4

Helix

333 – 335

3

Helix

336 – 343

8

Helix

359 – 363

5

Beta strand

372 – 375

4

Turn

382 – 384

3

Beta strand

387 – 391

5

Beta strand

394 – 400

7

Helix

404 – 406

3

Helix

412 – 414

3

Beta strand

421 – 430

10

Turn

431 – 433

3

Helix

450 – 469

20

Helix

477 – 479

3

Helix

483 – 485

3

Turn

496 – 499

4

Sequences

	Sequence		Length	Mass (Da)
	P15289 [UniParc]. Last modified February 1, 1991. Version 3. Checksum: 3DDBE1378B4176A6	FASTA	507	53,588
	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

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: 2562955] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of the arylsulfatase A gene." Kreysing J., von Figura K., Gieselmann V. Eur. J. Biochem. 191:627-631(1990) [PubMed: 1975241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	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.
[6]	"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. , 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: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-391. Tissue: B-cell.
[8]	"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: 1352993] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-33 AND 434-479, SUBUNIT.
[9]	"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: 7628016] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, OXOALANINE AT CYS-69, ABSENCE OF OXOALANINE IN MSD.
[10]	"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: 15146462] [Abstract] Cited for: INVOLVEMENT IN MSD.
[11]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-158 AND ASN-350, MASS SPECTROMETRY. Tissue: Liver.
[12]	"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: 9521684] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), OLIGOMERIZATION.
[13]	"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: 11124905] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS), MUTAGENESIS OF CYS-69.
[14]	"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: 12888274] [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.
[15]	"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: 16368756] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 69-73 IN COMPLEX WITH SUMF1.
[16]	"Molecular genetics of metachromatic leukodystrophy." Gieselmann V., Zlotogora J., Harris A., Wenger D.A., Morris C.P. Hum. Mutat. 4:233-242(1994) [PubMed: 7866401] [Abstract] Cited for: REVIEW ON MLD VARIANTS.
[17]	"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: 2574462] [Abstract] Cited for: VARIANT SER-350, ASSOCIATION WITH ARYLSULFATASE A PSEUDODEFICIENCY.
[18]	"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: 1673291] [Abstract] Cited for: VARIANT MLD ASP-99.
[19]	"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: 1678251] [Abstract] Cited for: VARIANT MLD PHE-96.
[20]	"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: 1670590] [Abstract] Cited for: VARIANT MLD LEU-426, VARIANTS CYS-193 AND SER-391.
[21]	"Late-onset metachromatic leukodystrophy: molecular pathology in two siblings." Kappler J., von Figura K., Gieselmann V. Ann. Neurol. 31:256-261(1992) [PubMed: 1353340] [Abstract] Cited for: VARIANT MLD GLN-84.
[22]	"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: 8101038] [Abstract] Cited for: VARIANT MLD SER-309.
[23]	"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: 8101083] [Abstract] Cited for: VARIANT MLD ARG-245.
[24]	"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: 8095918] [Abstract] Cited for: VARIANT MLD LEU-426.
[25]	"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: 7902317] [Abstract] Cited for: VARIANT MLD SER-122.
[26]	"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: 7906588] [Abstract] Cited for: VARIANTS MLD VAL-212; VAL-224 AND TYR-295.
[27]	"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: 8104633] [Abstract] Cited for: VARIANT MLD MET-274.
[28]	"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: 7909527] [Abstract] Cited for: VARIANT MLD ILE-409.
[29]	"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: 7825603] [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.
[30]	"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: 7860068] [Abstract] Cited for: VARIANT MLD LEU-136.
[31]	"Identification of seven novel mutations associated with metachromatic leukodystrophy." Barth M.L., Fensom A., Harris A. Hum. Mutat. 6:170-176(1995) [PubMed: 7581401] [Abstract] Cited for: VARIANTS MLD LEU-82; TYR-172; CYS-201; GLN-311; VAL-335 AND TRP-390.
[32]	"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: 8891236] [Abstract] Cited for: VARIANTS MLD HIS-153 AND VAL-308, CHARACTERIZATION OF VARIANTS MLD HIS-153 AND VAL-308.
[33]	"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: 8723680] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS MET-274 AND VAL-335.
[34]	"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: 9272717] [Abstract] Cited for: VARIANT MLD PRO-428.
[35]	"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: 9090526] [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.
[36]	"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: 9490297] [Abstract] Cited for: VARIANT MLD 406-SER--THR-408 DEL.
[37]	"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: 9600244] [Abstract] Cited for: VARIANTS MLD PRO-135 AND SER-179.
[38]	Erratum Gomez-Lira M., Perusi C., Mottes M., Pignatti P.F., Manfredi M., Rizzuto N., Salviati A. Hum. Genet. 102:602-602(1998)
[39]	"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: 9744473] [Abstract] Cited for: VARIANT HIS-496.
[40]	"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: 9452102] [Abstract] Cited for: VARIANTS MLD GLN-390 AND TYR-397.
[41]	"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: 9819708] [Abstract] Cited for: VARIANT MLD SER-298, CHARACTERIZATION OF VARIANT MLD SER-298.
[42]	"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: 9888390] [Abstract] Cited for: VARIANTS PRO-76; CYS-193; SER-391 AND VAL-464.
[43]	"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: 10220151] [Abstract] Cited for: VARIANTS MLD PHE-300 AND THR-425.
[44]	"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: 10477432] [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.
[45]	"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: 10533072] [Abstract] Cited for: VARIANTS MLD SER-179 AND TYR-281.
[46]	"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: 10381328] [Abstract] Cited for: VARIANTS MLD LEU-148; THR-191; VAL-335; TYR-397 AND LEU-426.
[47]	"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: 10751093] [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.
[48]	"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: 11061266] [Abstract] Cited for: VARIANT MLD PRO-286, VARIANT SER-391.
[49]	"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: 11020646] [Abstract] Cited for: VARIANT MLD GLY-143, CHARACTERIZATION OF VARIANT MLD GLY-143.
[50]	"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: 11456299] [Abstract] Cited for: VARIANT MLD ILE-408, VARIANTS CYS-193 AND SER-391.
[51]	"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: 11941485] [Abstract] Cited for: VARIANT MLD LYS-253, VARIANTS SER-350; SER-391 AND LEU-426.
[52]	"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: 12503099] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS MLD PHE-300 AND THR-425.
[53]	"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: 12788103] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS MLD PHE-300 AND THR-425.
[54]	"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: 14517960] [Abstract] Cited for: VARIANTS MLD LEU-155; GLN-181; VAL-212; HIS-306; SER-325; VAL-335; LEU-426 AND SER-429.
[55]	"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: 14680985] [Abstract] Cited for: VARIANTS MLD SER-136; SER-247; GLU-381 LEU-426 AND GLY-469.
[56]	"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: 15326627] [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.
[57]	"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: 15026521] [Abstract] Cited for: VARIANTS MLD ASP-293 AND GLY-489, VARIANT SER-350.
[58]	"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: 15710861] [Abstract] Cited for: VARIANT MLD VAL-219, CHARACTERIZATION OF VARIANT MLD VAL-219.
[59]	"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: 18693274] [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.
[60]	"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: 19606494] [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.
[61]	"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: 20339381] [Abstract] Cited for: VARIANTS MLD SER-179; SER-247; CYS-288; VAL-335; LYS-382; GLN-390; TRP-390; TYR-397 AND LEU-426.
[62]	"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: 21265945] [Abstract] Cited for: VARIANTS MLD ASP-99 AND ILE-409.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Wikipedia

Arylsulfatase A entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52151 mRNA. Translation: CAA36399.1.
X52150 Genomic DNA. Translation: CAA36398.1.
CR456383 mRNA. Translation: CAG30269.1.
AK315011 mRNA. Translation: BAG37503.1.
AY271820 Genomic DNA. Translation: AAP03431.1.
U62317 Genomic DNA. Translation: AAB03341.1. Different initiation.
BC014210 mRNA. Translation: AAH14210.2.

IPI

IPI00744184.

PIR

KJHUAA. S11031.

RefSeq

NP_000478.3. NM_000487.5.
NP_001078894.2. NM_001085425.2.
NP_001078895.2. NM_001085426.2.
NP_001078896.2. NM_001085427.2.

UniGene

Hs.731715.
Hs.88251.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AUK	X-ray	2.10	A	19-507	[»]
1E1Z	X-ray	2.40	P	19-507	[»]
1E2S	X-ray	2.35	P	19-507	[»]
1E33	X-ray	2.50	P	19-507	[»]
1E3C	X-ray	2.65	P	19-507	[»]
1N2K	X-ray	2.75	A	19-507	[»]
1N2L	X-ray	3.20	A	19-507	[»]
2AIJ	X-ray	1.55	P	69-73	[»]
2AIK	X-ray	1.73	P	68-74	[»]

ProteinModelPortal

P15289.

SMR

P15289. Positions 19-504.

ModBase

Search...

Protein-protein interaction databases

IntAct

P15289. 4 interactions.

STRING

P15289.

PTM databases

GlycoSuiteDB

P15289.

Proteomic databases

PRIDE

P15289.

Protocols and materials databases

DNASU

410.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216124; ENSP00000216124; ENSG00000100299.
ENST00000356098; ENSP00000348406; ENSG00000100299.
ENST00000395619; ENSP00000378981; ENSG00000100299.
ENST00000395621; ENSP00000378983; ENSG00000100299.
ENST00000395624; ENSP00000378986; ENSG00000100299.

GeneID

410.

KEGG

hsa:410.

UCSC

uc003bna.4. human.

Organism-specific databases

CTD

410.

GeneCards

GC22M051063.

H-InvDB

HIX0016620.

HGNC

HGNC:713. ARSA.

HPA

CAB025183.
HPA005554.

MIM

250100. phenotype.
272200. phenotype.
607574. gene.

neXtProt

NX_P15289.

Orphanet

512. Metachromatic leukodystrophy.
751. Pseudoarylsulfatase A deficiency.

PharmGKB

PA25005.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3119.

GeneTree

ENSGT00560000076940.

HOGENOM

HOG000135352.

HOVERGEN

HBG004283.

InParanoid

P15289.

KO

K01134.

OrthoDB

EOG4MKNG4.

PhylomeDB

P15289.

Enzyme and pathway databases

BRENDA

3.1.6.8. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P15289.

Bgee

P15289.

CleanEx

HS_ARSA.

Genevestigator

P15289.

GermOnline

ENSG00000100299. Homo sapiens.

Family and domain databases

Gene3D

G3DSA:3.40.720.10. Alk_phosphtse. 1 hit.

InterPro

IPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR000917. Sulfatase.
IPR024607. Sulfatase_CS.
[Graphical view]

Pfam

PF00884. Sulfatase. 1 hit.
[Graphical view]

SUPFAM

SSF53649. Alkaline_phosphatase_core. 1 hit.

PROSITE

PS00523. SULFATASE_1. 1 hit.
PS00149. SULFATASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01141. Micafungin.

EvolutionaryTrace

P15289.

NextBio

1725.

PMAP-CutDB

P15289.

SOURCE

Search...

Entry information

Entry name

ARSA_HUMAN

Accession

Primary (citable) accession number: P15289
Secondary accession number(s): B2RCA6, Q6ICI5, Q96CJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	February 1, 1991
Last modified:	May 16, 2012
This is version 143 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.