Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Biosynthesis of dermatan sulfate: Chondroitin glucuronate C5-epimerase is identical to SART2.

Maccarana, Marco LU ; Olander, Benny ; Malmström, Johan LU orcid ; Tiedemann, Kerstin LU ; Aebersold, Ruedi ; Lindahl, Ulf ; Li, Jin-Ping and Malmström, Anders LU orcid (2006) In Journal of Biological Chemistry 281(17). p.11560-11568
Abstract
We identified the gene encoding chondroitin-glucuronate C5-epimerase (EC 5.1.3.19 [EC] ) that converts D-glucuronic acid to L-iduronic acid residues in dermatan sulfate biosynthesis. The enzyme was solubilized from bovine spleen, and an ~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... (More)
We identified the gene encoding chondroitin-glucuronate C5-epimerase (EC 5.1.3.19 [EC] ) that converts D-glucuronic acid to L-iduronic acid residues in dermatan sulfate biosynthesis. The enzyme was solubilized from bovine spleen, and an ~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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
17
pages
11560 - 11568
publisher
ASBMB
external identifiers
  • wos:000236988100018
  • scopus:33744960214
ISSN
1083-351X
DOI
10.1074/jbc.M513373200
language
English
LU publication?
yes
id
5b8ef3c3-ece8-4137-bfb3-baca6312bf2d (old id 154919)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16505484&dopt=Abstract
date added to LUP
2016-04-01 11:53:41
date last changed
2021-10-06 02:47:48
@article{5b8ef3c3-ece8-4137-bfb3-baca6312bf2d,
  abstract     = {We identified the gene encoding chondroitin-glucuronate C5-epimerase (EC 5.1.3.19 [EC] ) that converts D-glucuronic acid to L-iduronic acid residues in dermatan sulfate biosynthesis. The enzyme was solubilized from bovine spleen, and an ~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.},
  author       = {Maccarana, Marco and Olander, Benny and Malmström, Johan and Tiedemann, Kerstin and Aebersold, Ruedi and Lindahl, Ulf and Li, Jin-Ping and Malmström, Anders},
  issn         = {1083-351X},
  language     = {eng},
  number       = {17},
  pages        = {11560--11568},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Biosynthesis of dermatan sulfate: Chondroitin glucuronate C5-epimerase is identical to SART2.},
  url          = {https://lup.lub.lu.se/search/ws/files/2691025/625379.pdf},
  doi          = {10.1074/jbc.M513373200},
  volume       = {281},
  year         = {2006},
}