Document Detail


Biosynthesis of dermatan sulfate: chondroitin-glucuronate C5-epimerase is identical to SART2.
MedLine Citation:
PMID:  16505484     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We identified the gene encoding chondroitin-glucuronate C5-epimerase (EC 5.1.3.19) that converts D-glucuronic acid to L-iduronic acid residues in dermatan sulfate biosynthesis. The enzyme was solubilized from bovine spleen, and an approximately 43,000-fold purified preparation containing a major 89-kDa candidate component was subjected to mass spectrometry analysis of tryptic peptides. SART2 (squamous cell carcinoma antigen recognized by T cell 2), a protein with unknown function highly expressed in cancer cells and tissues, was identified by 18 peptides covering 26% of the sequence. Transient expression of cDNA resulted in a 22-fold increase in epimerase activity in 293HEK cell lysate. Moreover, overexpressing cells produced dermatan sulfate chains with 20% of iduronic acid-containing disaccharide units, as compared with 5% for mock-transfected cells. The iduronic acid residues were preferentially clustered in blocks, as in naturally occurring dermatan sulfate. Given the discovered identity, we propose to rename SART2 (Nakao, M., Shichijo, S., Imaizumi, T., Inoue, Y., Matsunaga, K., Yamada, A., Kikuchi, M., Tsuda, N., Ohta, K., Takamori, S., Yamana, H., Fujita, H., and Itoh, K. (2000) J. Immunol. 164, 2565-2574) with a functional designation, chondroitin-glucuronate C5-epimerase (or DS epimerase). DS epimerase activity is ubiquitously present in normal tissues, although with marked quantitative differences. It is highly homologous to part of the NCAG1 protein, encoded by the C18orf4 gene, genetically linked to bipolar disorder. NCAG1 also contains a putative chondroitin sulfate sulfotransferase domain and thus may be involved in dermatan sulfate biosynthesis. The functional relation between dermatan sulfate and cancer is unknown but may involve known iduronic acid-dependent interactions with growth factors, selectins, cytokines, or coagulation inhibitors.
Authors:
Marco Maccarana; Benny Olander; Johan Malmström; Kerstin Tiedemann; Ruedi Aebersold; Ulf Lindahl; Jin-Ping Li; Anders Malmström
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-24     Completed Date:  2006-07-05     Revised Date:  2007-07-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11560-8     Citation Subset:  IM    
Affiliation:
Department of Experimental Medical Science, Lund University, BMC C13, SE-221 84 Lund, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antigens, Neoplasm / chemistry*,  metabolism
Carbohydrate Epimerases / genetics,  isolation & purification,  metabolism*
Cattle
Cells, Cultured
DNA, Complementary
DNA-Binding Proteins / chemistry*,  metabolism
Dermatan Sulfate / biosynthesis*
Humans
Iduronic Acid / metabolism
Kidney / metabolism
Mass Spectrometry
Molecular Sequence Data
Muscles / metabolism
Neoplasm Proteins / chemistry*,  metabolism
Rats
Sequence Homology, Amino Acid
Spleen / enzymology
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/DNA, Complementary; 0/DNA-Binding Proteins; 0/Neoplasm Proteins; 24967-94-0/Dermatan Sulfate; 3402-98-0/Iduronic Acid; EC 5.1.3.-/Carbohydrate Epimerases; EC 5.1.3.-/chondroitin D-glucuronosyl 5-epimerase; EC 5.1.3.19/DSE protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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