title: Arylsulfatase D gene in Xp22.3 encodes two protein isoforms.
abstract: The human genome contains six arylsulfatase genes (ARSA-ARSF), of which four are clustered in a distal region of the short arm of the X chromosome (Xp22.3). They were probably generated by a series of evolutionary duplication events; their exon-intron boundaries are identical. Nevertheless, different transcript lengths and the absence of cross-hybridizations point to a specific function of each gene in human cell metabolism, and multiple transcripts suggest the coding of protein isoforms. We identified a novel protein isoform of the ARSD gene by isolation of a series of cDNA clones from a human testis cDNA library. The clones were only partially identical to another series of ARSD clones isolated earlier (now designated ARSDalpha clones). Their specific C-terminal region (1160 nt) encodes a novel ARSD peptide of 48 amino acids and was identified as part of intron 6 of the ARSD gene in Xp22.3. We therefore designate them ARSDbeta clones. Expression analyses of ARSDalpha and ARSDbeta by semiquantitative RT-PCR revealed the presence of both in multiple human tissues, although in different quantities. A physiologic substrate for arylsulfatase D proteins is not known. We therefore estimated their sulfatase activities in vitro with the aid of the 4-methylumbelliferyl sulfate (4-MUS) assay. Surprisingly, neither ARSD protein isoform demonstrated any sulfatase activity alone or in combination, although their catalytic peptide domain is strongly conserved in comparison with that of the other X-chromosomal arylsulfatase enzymes (ARSC, ARSE, ARSF), all of which are functionally active in the 4-MUS assay.
authors.affiliation: Institute of Human Genetics, University of Heidelberg, INF 328, D-69120 Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Urbitsch
authors.forename: M J
authors.initials: MJ
authors.lastname: Salzer
authors.forename: P
authors.initials: P
authors.lastname: Hirschmann
authors.forename: P H
authors.initials: PH
authors.lastname: Vogt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001192:Arylsulfatases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D020134:Catalytic Domain; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D015723:Gene Library; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000378:metabolism; D007438:Introns / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D014162:Transfection; D014960:X Chromosome / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; C019492:4-methylumbelliferyl sulfate; D006923:Hymecromone; D001192:Arylsulfatases