• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Nov 1990; 87(21): 8531–8535.
PMCID: PMC54990

Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA.

Abstract

Iduronate 2-sulfatase (IDS, EC 3.1.6.13) is required for the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations causing IDS deficiency in humans result in the lysosomal storage of these glycosaminoglycans and Hunter syndrome, an X chromosome-linked disease. We have isolated and sequenced a 2.3-kilobase cDNA clone coding for the entire sequence of human IDS. Analysis of the deduced 550-amino acid IDS precursor sequence indicates that IDS has a 25-amino acid amino-terminal signal sequence, followed by 8 amino acids that are removed from the proprotein. An internal proteolytic cleavage occurs to produce the mature IDS present in human liver shown to contain a 42-kDa polypeptide N-terminal to a 14-kDa polypeptide. The IDS sequence has strong sequence homology with other sulfatases (such as sea urchin arylsulfatase, human arylsulfatases A, B, and C, and human glucosamine 6-sulfatase), suggesting that the sulfatases comprise an evolutionarily related family of genes that arose by gene duplication and divergent evolution. The arylsulfatases have a greater homology with each other than with the non-arylsulfatases (IDS and glucosamine 6-sulfatase). The IDS cDNA detected RNA species of 5.7, 5.4, 2.1, and 1.4 kilobases in human placental RNA and revealed structural alterations and gross deletions of the IDS gene in many of the clinically severe Hunter syndrome patients studied.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Nelson PV, Carey WF, Morris CP, Pollard AC. Cystic fibrosis: prenatal diagnosis and carrier detection by DNA analysis. Med J Aust. 1989 Aug 7;151(3):126–131. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Bray Jeremy. Better safe than sorry. Nature. 1985 Mar 28;314(6009):310–310. [PubMed]
  • Lipman DJ, Altschul SF, Kececioglu JD. A tool for multiple sequence alignment. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4412–4415. [PMC free article] [PubMed]
  • Maruyama T, Gojobori T, Aota S, Ikemura T. Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res. 1986;14 (Suppl):r151–r197. [PMC free article] [PubMed]
  • Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. [PMC free article] [PubMed]
  • von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. [PMC free article] [PubMed]
  • Stein C, Gieselmann V, Kreysing J, Schmidt B, Pohlmann R, Waheed A, Meyer HE, O'Brien JS, von Figura K. Cloning and expression of human arylsulfatase A. J Biol Chem. 1989 Jan 15;264(2):1252–1259. [PubMed]
  • Peters C, Schmidt B, Rommerskirch W, Rupp K, Zühlsdorf M, Vingron M, Meyer HE, Pohlmann R, von Figura K. Phylogenetic conservation of arylsulfatases. cDNA cloning and expression of human arylsulfatase B. J Biol Chem. 1990 Feb 25;265(6):3374–3381. [PubMed]
  • Yen PH, Marsh B, Allen E, Tsai SP, Ellison J, Connolly L, Neiswanger K, Shapiro LJ. The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: evidence for an inversion of the Y chromosome during primate evolution. Cell. 1988 Dec 23;55(6):1123–1135. [PubMed]
  • Oshima A, Kyle JW, Miller RD, Hoffmann JW, Powell PP, Grubb JH, Sly WS, Tropak M, Guise KS, Gravel RA. Cloning, sequencing, and expression of cDNA for human beta-glucuronidase. Proc Natl Acad Sci U S A. 1987 Feb;84(3):685–689. [PMC free article] [PubMed]
  • Morreau H, Galjart NJ, Gillemans N, Willemsen R, van der Horst GT, d'Azzo A. Alternative splicing of beta-galactosidase mRNA generates the classic lysosomal enzyme and a beta-galactosidase-related protein. J Biol Chem. 1989 Dec 5;264(34):20655–20663. [PubMed]
  • Robertson DA, Freeman C, Nelson PV, Morris CP, Hopwood JJ. Human glucosamine-6-sulfatase cDNA reveals homology with steroid sulfatase. Biochem Biophys Res Commun. 1988 Nov 30;157(1):218–224. [PubMed]
  • Yen PH, Allen E, Marsh B, Mohandas T, Wang N, Taggart RT, Shapiro LJ. Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange. Cell. 1987 May 22;49(4):443–454. [PubMed]
  • Stein C, Hille A, Seidel J, Rijnbout S, Waheed A, Schmidt B, Geuze H, von Figura K. Cloning and expression of human steroid-sulfatase. Membrane topology, glycosylation, and subcellular distribution in BHK-21 cells. J Biol Chem. 1989 Aug 15;264(23):13865–13872. [PubMed]
  • Sasaki H, Yamada K, Akasaka K, Kawasaki H, Suzuki K, Saito A, Sato M, Shimada H. cDNA cloning, nucleotide sequence and expression of the gene for arylsulfatase in the sea urchin (Hemicentrotus pulcherrimus) embryo. Eur J Biochem. 1988 Oct 15;177(1):9–13. [PubMed]
  • Lee GD, van Etten RL. Evidence of an essential histidine residue in rabbit liver aryl sulfatase A. Arch Biochem Biophys. 1975 Dec;171(2):424–434. [PubMed]
  • James GT. Essential arginine residues in human liver arylsulfatase A. Arch Biochem Biophys. 1979 Oct 1;197(1):57–62. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    Compound
    PubChem Compound links
  • Gene
    Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM
    OMIM record citing PubMed
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...