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. 1995 Dec 5;92(25):11766–11770. doi: 10.1073/pnas.92.25.11766

Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme.

M Misago 1, Y F Liao 1, S Kudo 1, S Eto 1, M G Mattei 1, K W Moremen 1, M N Fukuda 1
PMCID: PMC40483  PMID: 8524845

Abstract

Golgi alpha-mannosidase II (alpha-MII) is an enzyme involved in the processing of N-linked glycans. Using a previously isolated murine cDNA clone as a probe, we have isolated cDNA clones encompassing the human alpha-MII cDNA open reading frame and initiated isolation of human genomic clones. During the isolation of genomic clones, genes related to that encoding alpha-MII were isolated. One such gene was found to encode an isozyme, designated alpha-MIIx. A 5-kb cDNA clone encoding alpha-MIIx was then isolated from a human melanoma cDNA library. However, comparison between alpha-MIIx and alpha-MII cDNAs suggested that the cloned cDNA encodes a truncated polypeptide with 796 amino acid residues, while alpha-MII consists of 1144 amino acid residues. To reevaluate the sequence of alpha-MIIx cDNA, polymerase chain reaction (PCR) was performed with lymphocyte mRNAs. Comparison of the sequence of PCR products with the alpha-MIIx genomic sequence revealed that alternative splicing of the alpha-MIIx transcript can result in an additional transcript encoding a 1139-amino acid polypeptide. Northern analysis showed transcription of alpha-MIIx in various tissues, suggesting that the alpha-MIIx gene is a housekeeping gene. COS cells transfected with alpha-MIIx cDNA containing the full-length open reading frame showed an increase of alpha-mannosidase activity. The alpha-MIIx gene was mapped to human chromosome 15q25, whereas the alpha-MII gene was mapped to 5q21-22.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bause E., Bieberich E., Rolfs A., Völker C., Schmidt B. Molecular cloning and primary structure of Man9-mannosidase from human kidney. Eur J Biochem. 1993 Oct 15;217(2):535–540. doi: 10.1111/j.1432-1033.1993.tb18274.x. [DOI] [PubMed] [Google Scholar]
  2. Bischoff J., Moremen K., Lodish H. F. Isolation, characterization, and expression of cDNA encoding a rat liver endoplasmic reticulum alpha-mannosidase. J Biol Chem. 1990 Oct 5;265(28):17110–17117. [PubMed] [Google Scholar]
  3. Camirand A., Heysen A., Grondin B., Herscovics A. Glycoprotein biosynthesis in Saccharomyces cerevisiae. Isolation and characterization of the gene encoding a specific processing alpha-mannosidase. J Biol Chem. 1991 Aug 15;266(23):15120–15127. [PubMed] [Google Scholar]
  4. Crookston J. H., Crookston M. C., Burnie K. L., Francombe W. H., Dacie J. V., Davis J. A., Lewis S. M. Hereditary erythroblastic multinuclearity associated with a positive acidified-serum test: a type of congenital dyserythropoietic anaemia. Br J Haematol. 1969 Jul;17(1):11–26. doi: 10.1111/j.1365-2141.1969.tb05660.x. [DOI] [PubMed] [Google Scholar]
  5. Daniel P. F., Winchester B., Warren C. D. Mammalian alpha-mannosidases--multiple forms but a common purpose? Glycobiology. 1994 Oct;4(5):551–566. doi: 10.1093/glycob/4.5.551. [DOI] [PubMed] [Google Scholar]
  6. Fukuda M. N., Gaetani G. F., Izzo P., Scartezzini P., Dell A. Incompletely processed N-glycans of serum glycoproteins in congenital dyserythropoietic anaemia type II (HEMPAS). Br J Haematol. 1992 Dec;82(4):745–752. doi: 10.1111/j.1365-2141.1992.tb06953.x. [DOI] [PubMed] [Google Scholar]
  7. Fukuda M. N. HEMPAS disease: genetic defect of glycosylation. Glycobiology. 1990 Sep;1(1):9–15. doi: 10.1093/glycob/1.1.9. [DOI] [PubMed] [Google Scholar]
  8. Fukuda M. N., Klier G., Yu J., Scartezzini P. Anomalous clustering of underglycosylated band 3 in erythrocytes and their precursor cells in congenital dyserythropoietic anemia type II. Blood. 1986 Aug;68(2):521–529. [PubMed] [Google Scholar]
  9. Fukuda M. N., Masri K. A., Dell A., Luzzatto L., Moremen K. W. Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7443–7447. doi: 10.1073/pnas.87.19.7443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Herscovics A., Schneikert J., Athanassiadis A., Moremen K. W. Isolation of a mouse Golgi mannosidase cDNA, a member of a gene family conserved from yeast to mammals. J Biol Chem. 1994 Apr 1;269(13):9864–9871. [PubMed] [Google Scholar]
  11. Kornfeld R., Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. doi: 10.1146/annurev.bi.54.070185.003215. [DOI] [PubMed] [Google Scholar]
  12. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  13. Lal A., Schutzbach J. S., Forsee W. T., Neame P. J., Moremen K. W. Isolation and expression of murine and rabbit cDNAs encoding an alpha 1,2-mannosidase involved in the processing of asparagine-linked oligosaccharides. J Biol Chem. 1994 Apr 1;269(13):9872–9881. [PubMed] [Google Scholar]
  14. Metzler M., Gertz A., Sarkar M., Schachter H., Schrader J. W., Marth J. D. Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development. EMBO J. 1994 May 1;13(9):2056–2065. doi: 10.1002/j.1460-2075.1994.tb06480.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moremen K. W. Isolation of a rat liver Golgi mannosidase II clone by mixed oligonucleotide-primed amplification of cDNA. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5276–5280. doi: 10.1073/pnas.86.14.5276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moremen K. W., Robbins P. W. Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans. J Cell Biol. 1991 Dec;115(6):1521–1534. doi: 10.1083/jcb.115.6.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moremen K. W., Touster O. Biosynthesis and modification of Golgi mannosidase II in HeLa and 3T3 cells. J Biol Chem. 1985 Jun 10;260(11):6654–6662. [PubMed] [Google Scholar]
  18. Moremen K. W., Touster O., Robbins P. W. Novel purification of the catalytic domain of Golgi alpha-mannosidase II. Characterization and comparison with the intact enzyme. J Biol Chem. 1991 Sep 5;266(25):16876–16885. [PubMed] [Google Scholar]
  19. Moremen K. W., Trimble R. B., Herscovics A. Glycosidases of the asparagine-linked oligosaccharide processing pathway. Glycobiology. 1994 Apr;4(2):113–125. doi: 10.1093/glycob/4.2.113. [DOI] [PubMed] [Google Scholar]
  20. Nebes V. L., Schmidt M. C. Human lysosomal alpha-mannosidase: isolation and nucleotide sequence of the full-length cDNA. Biochem Biophys Res Commun. 1994 Apr 15;200(1):239–245. doi: 10.1006/bbrc.1994.1440. [DOI] [PubMed] [Google Scholar]
  21. Nguyen C., Mattei M. G., Mattei J. F., Santoni M. J., Goridis C., Jordan B. R. Localization of the human NCAM gene to band q23 of chromosome 11: the third gene coding for a cell interaction molecule mapped to the distal portion of the long arm of chromosome 11. J Cell Biol. 1986 Mar;102(3):711–715. doi: 10.1083/jcb.102.3.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schatzle J., Bush J., Cardelli J. Molecular cloning and characterization of the structural gene coding for the developmentally regulated lysosomal enzyme, alpha-mannosidase, in Dictyostelium discoideum. J Biol Chem. 1992 Feb 25;267(6):4000–4007. [PubMed] [Google Scholar]
  24. Velasco A., Hendricks L., Moremen K. W., Tulsiani D. R., Touster O., Farquhar M. G. Cell type-dependent variations in the subcellular distribution of alpha-mannosidase I and II. J Cell Biol. 1993 Jul;122(1):39–51. doi: 10.1083/jcb.122.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]

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