Iduronate-2-sulfatase explained

Iduronate 2-sulfatase (EC 3.1.6.13; systematic name L-iduronate-2-sulfate 2-sulfohydrolase) is a sulfatase enzyme associated with Hunter syndrome. It catalyses hydrolysis of the 2-sulfate groups of the L-iduronate 2-sulfate units of dermatan sulfate, heparan sulfate and heparin.

Function

Iduronate 2-sulfatase is required for the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this X-chromosome gene that result in enzymatic deficiency lead to the sex-linked mucopolysaccharidosis type II, also known as Hunter syndrome. At least 174 disease-causing mutations in this gene have been discovered.^[1] Iduronate-2-sulfatase has a strong sequence homology with human arylsulfatases A, B, and C, and human glucosamine-6-sulfatase. A splice variant of this gene has been described.^[2]

See also

• Idursulfase

References

Further reading

• Hopwood JJ, Bunge S, Morris CP, Wilson PJ, Steglich C, Beck M, Schwinger E, Gal A . Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate-2-sulphatase gene . Human Mutation . 2 . 6 . 435–42 . 1994 . 8111411 . 10.1002/humu.1380020603 . 19516545 . free .
• Gort L, Chabás A, Coll MJ . Hunter disease in the Spanish population: molecular analysis in 31 families . Journal of Inherited Metabolic Disease . 21 . 6 . 655–61 . Aug 1998 . 9762601 . 10.1023/A:1005432600871 . 3091580 .
• Crotty PL, Braun SE, Anderson RA, Whitley CB . Mutation R468W of the iduronate-2-sulfatase gene in mild Hunter syndrome (mucopolysaccharidosis type II) confirmed by in vitro mutagenesis and expression . Human Molecular Genetics . 1 . 9 . 755–7 . Dec 1992 . 1284597 . 10.1093/hmg/1.9.755 .
• Bunge S, Steglich C, Beck M, Rosenkranz W, Schwinger E, Hopwood JJ, Gal A . Mutation analysis of the iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II (Hunter syndrome) . Human Molecular Genetics . 1 . 5 . 335–9 . Aug 1992 . 1303211 . 10.1093/hmg/1.5.335 . free .
• Beck M, Steglich C, Zabel B, Dahl N, Schwinger E, Hopwood JJ, Gal A . Deletion of the Hunter gene and both DXS466 and DXS304 in a patient with mucopolysaccharidosis type II . American Journal of Medical Genetics . 44 . 1 . 100–3 . Sep 1992 . 1355630 . 10.1002/ajmg.1320440123 .
• Sukegawa K, Tomatsu S, Tamai K, Ikeda M, Sasaki T, Masue M, Fukuda S, Yamada Y, Orii T . Intermediate form of mucopolysaccharidosis type II (Hunter disease): a C1327 to T substitution in the iduronate sulfatase gene . Biochemical and Biophysical Research Communications . 183 . 2 . 809–13 . Mar 1992 . 1550586 . 10.1016/0006-291X(92)90555-Y .
• Flomen RH, Green PM, Bentley DR, Giannelli F, Green EP . Detection of point mutations and a gross deletion in six Hunter syndrome patients . Genomics . 13 . 3 . 543–50 . Jul 1992 . 1639384 . 10.1016/0888-7543(92)90123-A .
• Wilson PJ, Suthers GK, Callen DF, Baker E, Nelson PV, Cooper A, Wraith JE, Sutherland GR, Morris CP, Hopwood JJ . Grant Robert Sutherland . Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome . Human Genetics . 86 . 5 . 505–8 . Mar 1991 . 1901826 . 10.1007/BF00194643 . 12618996 .
• Wraith JE, Cooper A, Thornley M, Wilson PJ, Nelson PV, Morris CP, Hopwood JJ . The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome) . Human Genetics . 87 . 2 . 205–6 . Jun 1991 . 1906048 . 10.1007/BF00204183 . 44338173 .
• Wilson PJ, Morris CP, Anson DS, Occhiodoro T, Bielicki J, Clements PR, Hopwood JJ . Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA . Proceedings of the National Academy of Sciences of the United States of America . 87 . 21 . 8531–5 . Nov 1990 . 2122463 . 54990 . 10.1073/pnas.87.21.8531 . 1990PNAS...87.8531W . free .
• Bielicki J, Freeman C, Clements PR, Hopwood JJ . Human liver iduronate-2-sulphatase. Purification, characterization and catalytic properties . The Biochemical Journal . 271 . 1 . 75–86 . Oct 1990 . 2222422 . 1149515 . 10.1042/bj2710075.
• Daniele A, Di Natale P . Hunter syndrome: presence of material cross-reacting with antibodies against iduronate sulfatase . Human Genetics . 75 . 3 . 234–8 . Mar 1987 . 3104200 . 10.1007/BF00281065 . 13349788 .
• Mossman J, Blunt S, Stephens R, Jones EE, Pembrey M . Hunter's disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene . Archives of Disease in Childhood . 58 . 11 . 911–5 . Nov 1983 . 6418082 . 1628393 . 10.1136/adc.58.11.911 .
• Sukegawa K, Tomatsu S, Fukao T, Iwata H, Song XQ, Yamada Y, Fukuda S, Isogai K, Orii T . Mucopolysaccharidosis type II (Hunter disease): identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients . Human Mutation . 6 . 2 . 136–43 . 1995 . 7581397 . 10.1002/humu.1380060206 . 10038064 . free .
• Li P, Huffman P, Thompson JN . Mutations of the iduronate-2-sulfatase gene on a T146T background in three patients with Hunter syndrome . Human Mutation . 5 . 3 . 272–4 . 1995 . 7599640 . 10.1002/humu.1380050314 . 30284511 .
• Popowska E, Rathmann M, Tylki-Szymanska A, Bunge S, Steglich C, Schwinger E, Gal A . Mutations of the iduronate-2-sulfatase gene in 12 Polish patients with mucopolysaccharidosis type II (Hunter syndrome) . Human Mutation . 5 . 1 . 97–100 . 1995 . 7728156 . 10.1002/humu.1380050114 . 2348885 . free .
• Ben Simon-Schiff E, Bach G, Hopwood JJ, Abeliovich D . Mutation analysis of Jewish Hunter patients in Israel . Human Mutation . 4 . 4 . 263–70 . 1995 . 7866405 . 10.1002/humu.1380040406 . 23243913 . free .
• Jonsson JJ, Aronovich EL, Braun SE, Whitley CB . Molecular diagnosis of mucopolysaccharidosis type II (Hunter syndrome) by automated sequencing and computer-assisted interpretation: toward mutation mapping of the iduronate-2-sulfatase gene . American Journal of Human Genetics . 56 . 3 . 597–607 . Mar 1995 . 7887413 . 1801163 .
• Schröder W, Wulff K, Wehnert M, Seidlitz G, Herrmann FH . Mutations of the iduronate-2-sulfatase (IDS) gene in patients with Hunter syndrome (mucopolysaccharidosis II) . Human Mutation . 4 . 2 . 128–31 . 1994 . 7981716 . 10.1002/humu.1380040206 . 42344223 . free .

External links

• GeneReviews/NIH/NCBI/UW entry on Mucopolysaccharidosis Type II

Notes and References

1. Šimčíková D, Heneberg P . Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases . Scientific Reports . 9 . 1 . 18577 . December 2019 . 31819097 . 6901466 . 10.1038/s41598-019-54976-4. 2019NatSR...918577S .
2. Web site: Entrez Gene: IDS iduronate 2-sulfatase (Hunter syndrome).