NCU-G1 is a highly glycosylated integral membrane protein of the lysosome.

Schieweck O, Damme M, Schröder B, Hasilik A, Schmidt B, Lübke T (2009)
Biochemical Journal 422(1): 83-90.

Journal Article | Published | English

No fulltext has been uploaded

; ; ; ; ;
Until recently, a modest number of approx. 40 lysosomal membrane proteins had been identified and even fewer were characterized in their function. In a proteomic study, using lysosomal membranes from human placenta we identified several candidate lysosomal membrane proteins and proved the lysosomal localization of two of them. In the present study, we demonstrate the lysosomal localization of the mouse orthologue of the human C1orf85 protein, which has been termed kidney-predominant protein NCU-G1 (GenBank accession number: AB027141). NCU-G1 encodes a 404 amino acid protein with a calculated molecular mass of 39 kDa. The bioinformatics analysis of its amino acid sequence suggests it is a type I transmembrane protein containing a single tyrosine-based consensus lysosomal sorting motif at position 400 within the 12-residue C-terminal tail. Its lysosomal localization was confirmed using immunofluorescence with a C-terminally His-tagged NCU-G1 and the lysosomal marker LAMP-1 (lysosome-associated membrane protein-1) as a reference, and by subcellular fractionation of mouse liver after a tyloxapol-induced density shift of the lysosomal fraction using an anti-NCU-G1 antiserum. In transiently transfected HT1080 and HeLa cells, the His-tagged NCU-G1 was detected in two molecular forms with apparent protein sizes of 70 and 80 kDa, and in mouse liver the endogenous wild-type NCU-G1 was detected as a 75 kDa protein. The remarkable difference between the apparent and the calculated molecular masses of NCU-G1 was shown, by digesting the protein with N-glycosidase F, to be due to an extensive glycosylation. The lysosomal localization was impaired by mutational replacement of an alanine residue for the tyrosine residue within the putative sorting motif.
Publishing Year

Cite this

Schieweck O, Damme M, Schröder B, Hasilik A, Schmidt B, Lübke T. NCU-G1 is a highly glycosylated integral membrane protein of the lysosome. Biochemical Journal. 2009;422(1):83-90.
Schieweck, O., Damme, M., Schröder, B., Hasilik, A., Schmidt, B., & Lübke, T. (2009). NCU-G1 is a highly glycosylated integral membrane protein of the lysosome. Biochemical Journal, 422(1), 83-90.
Schieweck, O., Damme, M., Schröder, B., Hasilik, A., Schmidt, B., and Lübke, T. (2009). NCU-G1 is a highly glycosylated integral membrane protein of the lysosome. Biochemical Journal 422, 83-90.
Schieweck, O., et al., 2009. NCU-G1 is a highly glycosylated integral membrane protein of the lysosome. Biochemical Journal, 422(1), p 83-90.
O. Schieweck, et al., “NCU-G1 is a highly glycosylated integral membrane protein of the lysosome.”, Biochemical Journal, vol. 422, 2009, pp. 83-90.
Schieweck, O., Damme, M., Schröder, B., Hasilik, A., Schmidt, B., Lübke, T.: NCU-G1 is a highly glycosylated integral membrane protein of the lysosome. Biochemical Journal. 422, 83-90 (2009).
Schieweck, Oliver, Damme, Markus, Schröder, Bernd, Hasilik, Andrey, Schmidt, Bernhard, and Lübke, Torben. “NCU-G1 is a highly glycosylated integral membrane protein of the lysosome.”. Biochemical Journal 422.1 (2009): 83-90.
This data publication is cited in the following publications:
This publication cites the following data publications:

11 Citations in Europe PMC

Data provided by Europe PubMed Central.

The Arabidopsis tonoplast is almost devoid of glycoproteins with complex N-glycans, unlike the rat lysosomal membrane.
Pedrazzini E, Caprera A, Fojadelli I, Stella A, Rocchetti A, Bassin B, Martinoia E, Vitale A., J. Exp. Bot. 67(6), 2016
PMID: 26748395
Lack of the Lysosomal Membrane Protein, GLMP, in Mice Results in Metabolic Dysregulation in Liver.
Kong XY, Kase ET, Herskedal A, Schjalm C, Damme M, Nesset CK, Thoresen GH, Rustan AC, Eskild W., PLoS ONE 10(6), 2015
PMID: 26047317
Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease.
Peters J, Rittger A, Weisner R, Knabbe J, Zunke F, Rothaug M, Damme M, Berkovic SF, Blanz J, Saftig P, Schwake M., Biochem. Biophys. Res. Commun. 457(3), 2015
PMID: 25576872
Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells.
Kong XY, Nesset CK, Damme M, Loberg EM, Lubke T, Mæhlen J, Andersson KB, Lorenzo PI, Roos N, Thoresen GH, Rustan AC, Kase ET, Eskild W., Dis Model Mech 7(3), 2014
PMID: 24487409
Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease.
Damme M, Brandenstein L, Fehr S, Jankowiak W, Bartsch U, Schweizer M, Hermans-Borgmeyer I, Storch S., Neurobiol. Dis. 65(), 2014
PMID: 24423645
An extended proteome map of the lysosomal membrane reveals novel potential transporters.
Chapel A, Kieffer-Jaquinod S, Sagne C, Verdon Q, Ivaldi C, Mellal M, Thirion J, Jadot M, Bruley C, Garin J, Gasnier B, Journet A., Mol. Cell Proteomics 12(6), 2013
PMID: 23436907
Lysosomal membrane proteins and their central role in physiology.
Schwake M, Schroder B, Saftig P., Traffic 14(7), 2013
PMID: 23387372
TM7SF1 (GPR137B): a novel lysosome integral membrane protein.
Gao J, Xia L, Lu M, Zhang B, Chen Y, Xu R, Wang L., Mol. Biol. Rep. 39(9), 2012
PMID: 22729905
Disrupted in renal carcinoma 2 (DIRC2), a novel transporter of the lysosomal membrane, is proteolytically processed by cathepsin L.
Savalas LR, Gasnier B, Damme M, Lubke T, Wrocklage C, Debacker C, Jezegou A, Reinheckel T, Hasilik A, Saftig P, Schroder B., Biochem. J. 439(1), 2011
PMID: 21692750
Classification of subcellular location by comparative proteomic analysis of native and density-shifted lysosomes.
Della Valle MC, Sleat DE, Zheng H, Moore DF, Jadot M, Lobel P., Mol. Cell Proteomics 10(4), 2011
PMID: 21252268
The proteome of lysosomes.
Schroder BA, Wrocklage C, Hasilik A, Saftig P., Proteomics 10(22), 2010
PMID: 20957757

44 References

Data provided by Europe PubMed Central.

Lysosomes and autophagy in cell death control.
Kroemer G, Jaattela M., Nat. Rev. Cancer 5(11), 2005
PMID: 16239905
Cathepsin-regulated apoptosis.
Chwieralski CE, Welte T, Buhling F., Apoptosis 11(2), 2006
PMID: 16502253
Intracellular localization of p40, a protein identified in a preparation of lysosomal membranes.
Boonen M, Hamer I, Boussac M, Delsaute AF, Flamion B, Garin J, Jadot M., Biochem. J. 395(1), 2006
PMID: 16367739
Demonstration of lysosomal localization for the mammalian ependymin-related protein using classical approaches combined with a novel density shift method.
Della Valle MC, Sleat DE, Sohar I, Wen T, Pintar JE, Jadot M, Lobel P., J. Biol. Chem. 281(46), 2006
PMID: 16954209
Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).
Fan X, Zhang H, Zhang S, Bagshaw RD, Tropak MB, Callahan JW, Mahuran DJ., Am. J. Hum. Genet. 79(4), 2006
PMID: 16960811
Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).
Hrebicek M, Mrazova L, Seyrantepe V, Durand S, Roslin NM, Noskova L, Hartmannova H, Ivanek R, Cizkova A, Poupetova H, Sikora J, Urinovska J, Stranecky V, Zeman J, Lepage P, Roquis D, Verner A, Ausseil J, Beesley CE, Maire I, Poorthuis BJ, van de Kamp J, van Diggelen OP, Wevers RA, Hudson TJ, Fujiwara TM, Majewski J, Morgan K, Kmoch S, Pshezhetsky AV., Am. J. Hum. Genet. 79(5), 2006
PMID: 17033958
The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter.
Siintola E, Topcu M, Aula N, Lohi H, Minassian BA, Paterson AD, Liu XQ, Wilson C, Lahtinen U, Anttonen AK, Lehesjoki AE., Am. J. Hum. Genet. 81(1), 2007
PMID: 17564970
Integral and associated lysosomal membrane proteins.
Schroder B, Wrocklage C, Pan C, Jager R, Kosters B, Schafer H, Elsasser HP, Mann M, Hasilik A., Traffic 8(12), 2007
PMID: 17897319
Human NCU-G1 can function as a transcription factor and as a nuclear receptor co-activator.
Steffensen KR, Bouzga M, Skjeldal F, Kasi C, Karahasan A, Matre V, Bakke O, Guerin S, Eskild W., BMC Mol. Biol. 8(), 2007
PMID: 18021396
LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.
Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, Brondyk W, Van Patten S, Edmunds T, Saftig P., Cell 131(4), 2007
PMID: 18022370
TMEM74, a lysosome and autophagosome protein, regulates autophagy.
Yu C, Wang L, Lv B, Lu Y, Zeng L, Chen Y, Ma D, Shi T, Wang L., Biochem. Biophys. Res. Commun. 369(2), 2008
PMID: 18294959
Molecular physiology and pathophysiology of lysosomal membrane transporters
Sagné, Journal of Inherited Metabolic Disease 31(2), 2008
Proteomics of the lysosome.
Lubke T, Lobel P, Sleat DE., Biochim. Biophys. Acta 1793(4), 2009
PMID: 18977398
Sorting of lysosomal proteins.
Braulke T, Bonifacino JS., Biochim. Biophys. Acta 1793(4), 2009
PMID: 19046998
Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism.
Rutsch F, Gailus S, Miousse IR, Suormala T, Sagne C, Toliat MR, Nurnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Hohne W, Gasnier B, Rosenblatt DS, Fowler B, Nurnberg P., Nat. Genet. 41(2), 2009
PMID: 19136951
Molecular characterization and gene disruption of mouse lysosomal putative serine carboxypeptidase 1.
Kollmann K, Damme M, Deuschl F, Kahle J, D'Hooge R, Lullmann-Rauch R, Lubke T., FEBS J. 276(5), 2009
PMID: 19187242
Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner.
Autefage H, Albinet V, Garcia V, Berges H, Nicolau ML, Therville N, Altie MF, Caillaud C, Levade T, Andrieu-Abadie N., J. Biol. Chem. 284(17), 2009
PMID: 19246452
A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, Science (), 2009


0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®


PMID: 19489740
PubMed | Europe PMC

Search this title in

Google Scholar