Linked Life Data

9988767

Source:http://linkedlifedata.com/resource/pubmed/id/9988767

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1999-3-18
pubmed:databankReference
pubmed:abstractText
3-O-Sulfated glucosaminyl residues are rare constituents of heparan sulfate and are essential for the activity of anticoagulant heparan sulfate. Cellular production of the critical active structure is controlled by the rate-limiting enzyme, heparan sulfate D-glucosaminyl 3-O-sulfotransferase-1 (3-OST-1) (EC 2.8.2.23). We have probed the expressed sequence tag data base with the carboxyl-terminal sulfotransferase domain of 3-OST-1 to reveal three novel, incomplete human cDNAs. These were utilized in library screens to isolate full-length cDNAs. Clones corresponding to predominant transcripts were obtained for the 367-, 406-, and 390-amino acid enzymes 3-OST-2, 3-OST-3A, and 3-OST-3B, respectively. These type II integral membrane proteins are comprised of a divergent amino-terminal region and a very homologous carboxyl-terminal sulfotransferase domain of approximately 260 residues. Also recovered were partial length clones for 3-OST-4. Expression of the full-length enzymes confirms the 3-O-sulfation of specific glucosaminyl residues within heparan sulfate (Liu, J., Shworak, N. W., Sinaÿ, P., Schwartz, J. J. Zhang, L., Fritze, L. M. S., and Rosenberg, R. D. (1999) J. Biol. Chem. 274, 5185-5192). Southern analyses suggest the human 3OST1, 3OST2, and 3OST4 genes, and the corresponding mouse isologs, are single copy. However, 3OST3A and 3OST3B genes are each duplicated in humans and show at least one copy each in mice. Intriguingly, the entire sulfotransferase domain sequence of the 3-OST-3B cDNA (774 base pairs) was 99.2% identical to the same region of 3-OST-3A. Together, these data argue that the structure of this functionally important region is actively maintained by gene conversion between 3OST3A and 3OST3B loci. Interspecific mouse back-cross analysis identified the loci for mouse 3Ost genes and syntenic assignments of corresponding human isologs were confirmed by the identification of mapped sequence-tagged site markers. Northern blot analyses indicate brain exclusive and brain predominant expression of 3-OST-4 and 3-OST-2 transcripts, respectively; whereas, 3-OST-3A and 3-OST-3B isoforms show widespread expression of multiple transcripts. The reiteration and conservation of the 3-OST sulfotransferase domain suggest that this structure is a self-contained functional unit. Moreover, the extensive number of 3OST genes with diverse expression patterns of multiple transcripts suggests that the novel 3-OST enzymes, like 3-OST-1, regulate important biologic properties of heparan sulfate proteoglycans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5170-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9988767-Amino Acid Sequence, pubmed-meshheading:9988767-Animals, pubmed-meshheading:9988767-Base Sequence, pubmed-meshheading:9988767-Blotting, Northern, pubmed-meshheading:9988767-Blotting, Southern, pubmed-meshheading:9988767-Chromosome Mapping, pubmed-meshheading:9988767-Cloning, Molecular, pubmed-meshheading:9988767-DNA, Complementary, pubmed-meshheading:9988767-Female, pubmed-meshheading:9988767-Humans, pubmed-meshheading:9988767-Isoenzymes, pubmed-meshheading:9988767-Male, pubmed-meshheading:9988767-Mice, pubmed-meshheading:9988767-Mice, Inbred C57BL, pubmed-meshheading:9988767-Molecular Sequence Data, pubmed-meshheading:9988767-Multigene Family, pubmed-meshheading:9988767-Protein Conformation, pubmed-meshheading:9988767-Sequence Homology, Amino Acid, pubmed-meshheading:9988767-Sulfotransferases
pubmed:year
1999
pubmed:articleTitle
Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase. Isolation, characterization, and expression of human cdnas and identification of distinct genomic loci.
pubmed:affiliation
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. nshworak@caregroup.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't