CoChat
Sign Up
Cited by 66

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions

Pedersen, Nis Borbye, Wang, Shengjun, Narimatsu, Yoshiki, Yang, Zhang, Halim, Adnan, Schjoldager, Katrine Ter-Borch Gram, Madsen, Thomas Daugbjerg, Seidah, Nabil G., Bennett, Eric Paul, Levery, Steven B., Clausen, Henrik·2014·Journal of Biological Chemistry
DOI 10.1074/jbc.m113.545053
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/jbc.m113.545053

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Glycosylation within the LDLR ligand binding domain enhances the ligand binding affinity of the LDLR.

    “Glycosylation (both N-linked and O-linked) within the ligand binding domain has been shown to enhance the ligand binding affinity of the LDLR [19–21].”

    From Post-translational regulation of the low-density lipoprotein receptor provides new targets for cholesterol regulation (2024) · cites this paper as [20]

    The Abstract reports O-glycosylation in linker regions of the LDLR ligand-binding domain, and the Results identify potential N-glycosylation sites in the same region. The paper does not show that either type enhances ligand-binding affinity; it says the functional role of the O-glycans remains unclear. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Modification by O-glycosylation enhances binding of apolipoprotein ligands to LDLR, likely largely mediated by the GalNAc-transferase GalNAc-T1.

    “Modification by O-glycosylation enhances binding of apolipoprotein ligands to LDLR, likely largely mediated by the GalNAc-transferase GalNaC-T1179,92.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [92]

    The Abstract reports O-glycosylation in LDLR’s ligand-binding domain and evidence that GalNAc-T11—not GalNAc-T1—plays a major role in glycosylating its linker regions. It says the biological significance of these glycans is not yet clear; it does not establish that they enhance apolipoprotein-ligand binding. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The ligand binding domain of LDLR has also been shown to be O-glycosylated.

    “In addition to the glycosylated region near the transmembrane domain, the ligand binding domain of LDLR has also been shown to be O-glycosylated79,92.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [92]

  • O-glycosylated chains of mLDLR are predominantly present close to the C-terminal transmembrane domain but are also found in linker regions separating the N-terminal repeat domains of the LDLR.

    “The latter are predominantly present close to the C-terminal transmembrane domain but are also found in the linker regions separating the N-terminal repeat domains of the LDLR (22).”

    From Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR cleaved by furin (2021) · cites this paper as [22]

  • Wildtype ASGR1 binds both immature non-O-glycosylated iLDLR (approximately 110 kDa) and mature mLDLR (approximately 150 kDa).

    “Immunoprecipitation with Flag antibody (ASGR1-Flag) and WB with antibodies for ASGR1 or LDLR (Fig. 8C; left panel) revealed that WT ASGR1 binds to both immature iLDLR (non-O-glycosylated; ∼110 kDa) and mature mLDLR (N- and O-glycosylated; ∼150 kDa) (22).”

    From Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR cleaved by furin (2021) · cites this paper as [22]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 59

  1. Goldstein, 2009, The LDL receptor, Arterioscler. Thromb. Vasc. Biol, 29, 431, 10.1161/ATVBAHA.108.179564 · DOI · Paper page
  2. Dieckmann, 2010, Lipoprotein receptors: an evolutionarily ancient multifunctional receptor family, Biol. Chem, 391, 1341, 10.1515/bc.2010.129 · DOI
  3. Chappell, 1992, The low density lipoprotein receptor-related protein/α2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase, J. Biol. Chem, 267, 25764, 10.1016/S0021-9258(18)35675-8 · DOI · Paper page
  4. Nykjaer, 1993, The α2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and β-migrating very low density lipoprotein associated with the lipase, J. Biol. Chem, 268, 15048, 10.1016/S0021-9258(18)82436-X · DOI
  5. Kounnas, 1995, The cellular internalization and degradation of hepatic lipase is mediated by low density lipoprotein receptor-related protein and requires cell surface proteoglycans, J. Biol. Chem, 270, 9307, 10.1074/jbc.270.16.9307 · DOI
  6. Vergés, 2004, Endocytosis of hepatic lipase and lipoprotein lipase into rat liver hepatocytes in vivo is mediated by the low density lipoprotein receptor-related protein, J. Biol. Chem, 279, 9030, 10.1074/jbc.M312908200 · DOI
  7. Jeon, 2005, Structure and physiologic function of the low-density lipoprotein receptor, Annu. Rev. Biochem, 74, 535, 10.1146/annurev.biochem.74.082803.133354 · DOI · Paper page
  8. Bu, 2001, The roles of receptor-associated protein (RAP) as a molecular chaperone for members of the LDL receptor family, Int. Rev. Cytol, 209, 79, 10.1016/S0074-7696(01)09011-8 · DOI
  9. Jensen, 2006, Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif, J. Mol. Biol, 362, 700, 10.1016/j.jmb.2006.07.013 · DOI
  10. Andersen, 2000, Specific binding of α-macroglobulin to complement-type repeat CR4 of the low-density lipoprotein receptor-related protein, Biochemistry, 39, 10627, 10.1021/bi000498h · DOI
  11. Iijima, 1998, Expression and characterization of a very low density lipoprotein receptor variant lacking the O-linked sugar region generated by alternative splicing, J. Biochem, 124, 747, 10.1093/oxfordjournals.jbchem.a022175 · DOI
  12. Kozarsky, 1988, Use of a mutant cell line to study the kinetics and function of O-linked glycosylation of low density lipoprotein receptors, Proc. Natl. Acad. Sci. U.S.A, 85, 4335, 10.1073/pnas.85.12.4335 · DOI
  13. Kingsley, 1986, Reversible defects in O-linked glycosylation and LDL receptor expression in a UDP-Gal/UDP-GalNAc 4-epimerase deficient mutant, Cell, 44, 749, 10.1016/0092-8674(86)90841-X · DOI
  14. Davis, 1986, Deletion of clustered O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibroblasts, J. Biol. Chem, 261, 2828, 10.1016/S0021-9258(17)35862-3 · DOI
  15. Seguchi, 1991, The dysfunctional LDL receptor in a monensin-resistant mutant of Chinese hamster ovary cells lacks selected O-linked oligosaccharides, Arch. Biochem. Biophys, 284, 245, 10.1016/0003-9861(91)90292-Q · DOI
  16. Yoshimura, 1987, Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chinese hamster ovary cells, J. Biol. Chem, 262, 13299, 10.1016/S0021-9258(18)45201-5 · DOI
  17. Tomita, 1987, Chinese hamster ovary cell mutant with defective down-regulation of low density lipoprotein receptors, J. Biol. Chem, 262, 1398, 10.1016/S0021-9258(19)75799-8 · DOI
  18. Steentoft, 2013, Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology, EMBO J, 32, 1478, 10.1038/emboj.2013.79 · DOI · Paper page
  19. Steentoft, 2011, Mining the O-glycoproteome using zinc-finger nuclease-glycoengineered SimpleCell lines, Nat. Methods, 8, 977, 10.1038/nmeth.1731 · DOI
  20. Vakhrushev, 2013, Enhanced mass spectrometric mapping of the human GalNAc-type O-glycoproteome with SimpleCells, Mol. Cell Proteomics, 12, 932, 10.1074/mcp.O112.021972 · DOI
  21. Ju, 2005, Protein glycosylation: chaperone mutation in Tn syndrome, Nature, 437, 1252, 10.1038/4371252a · DOI
  22. Canuel, 2013, Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1), PLoS One, 8, e64145, 10.1371/journal.pone.0064145 · DOI · Paper page
  23. Liu, 2007, Bacterial glycosidases for the production of universal red blood cells, Nat. Biotechnol, 25, 454, 10.1038/nbt1298 · DOI
  24. Tarp, 2007, Identification of a novel cancer-specific immunodominant glycopeptide epitope in the MUC1 tandem repeat, Glycobiology, 17, 197, 10.1093/glycob/cwl061 · DOI
  25. Schwientek, 2002, Functional conservation of subfamilies of putative UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases in Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of l(2)35Aa is essential in Drosophila, J. Biol. Chem, 277, 22623, 10.1074/jbc.M202684200 · DOI · Paper page
  26. Schjoldager, 2012, Probing isoform-specific functions of polypeptide GalNAc-transferases using zinc finger nuclease glycoengineered SimpleCells, Proc. Natl. Acad. Sci. U.S.A, 109, 9893, 10.1073/pnas.1203563109 · DOI
  27. Cummings, 1983, Biosynthesis of N- and O-linked oligosaccharides of the low density lipoprotein receptor, J. Biol. Chem, 258, 15261, 10.1016/S0021-9258(17)43802-6 · DOI
  28. Liu, 2005, Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry, J. Proteome Res, 4, 2070, 10.1021/pr0502065 · DOI
  29. Zhang, 2003, Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry, Nat. Biotechnol, 21, 660, 10.1038/nbt827 · DOI
  30. Chen, 2009, Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry, J. Proteome Res, 8, 651, 10.1021/pr8008012 · DOI
  31. Bennett, 2012, Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family, Glycobiology, 22, 736, 10.1093/glycob/cwr182 · DOI · Paper page
  32. Tran, 2013, Mucin-type O-glycosylation during development, J. Biol. Chem, 288, 6921, 10.1074/jbc.R112.418558 · DOI
  33. Nilsson, 2009, Enrichment of glycopeptides for glycan structure and attachment site identification, Nat. Methods, 6, 809, 10.1038/nmeth.1392 · DOI
  34. Darula, 2012, How to dig deeper? Improved enrichment methods for mucin core-1 type glycopeptides, Mol. Cell. Proteomics, 11, 10.1074/mcp.O111.016774 · DOI
  35. Rudenko, 2002, Structure of the LDL receptor extracellular domain at endosomal pH, Science, 298, 2353, 10.1126/science.1078124 · DOI · Paper page
  36. Gerken, 2011, Emerging paradigms for the initiation of mucin-type protein O-glycosylation by the polypeptide GalNAc transferase family of glycosyltransferases, J. Biol. Chem, 286, 14493, 10.1074/jbc.M111.218701 · DOI
  37. Gerken, 2008, Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs, Glycobiology, 18, 861, 10.1093/glycob/cwn073 · DOI
  38. Gerken, 2006, Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferases T1 and T2 derived from oriented random peptide substrates, J. Biol. Chem, 281, 32403, 10.1074/jbc.M605149200 · DOI
  39. Takeuchi, 2010, Role of glycosylation of Notch in development, Semin. Cell Dev. Biol, 21, 638, 10.1016/j.semcdb.2010.03.003 · DOI
  40. Julenius, 2005, Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites, Glycobiology, 15, 153, 10.1093/glycob/cwh151 · DOI
  41. Lewis, 2013, Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome, Nat. Biotechnol, 31, 759, 10.1038/nbt.2624 · DOI · Paper page
  42. Zhang, 2003, Cloning and characterization of a new human UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase, designated pp-GalNAc-T13, that is specifically expressed in neurons and synthesizes GalNAc α-serine/threonine antigen, J. Biol. Chem, 278, 573, 10.1074/jbc.M203094200 · DOI
  43. Tenno, 2007, Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity, Mol. Cell Biol, 27, 8783, 10.1128/MCB.01204-07 · DOI
  44. Ichikawa, 2009, Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression, Endocrinology, 150, 2543, 10.1210/en.2008-0877 · DOI
  45. Gill, 2011, Location, location, location: new insights into O-GalNAc protein glycosylation, Trends Cell Biol, 21, 149, 10.1016/j.tcb.2010.11.004 · DOI
  46. Topaz, 2004, Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis, Nat. Genet, 36, 579, 10.1038/ng1358 · DOI
  47. Kato, 2006, Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation, J. Biol. Chem, 281, 18370, 10.1074/jbc.M602469200 · DOI
  48. Fakhro, 2011, Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning, Proc. Natl. Acad. Sci. U.S.A, 108, 2915, 10.1073/pnas.1019645108 · DOI
  49. Boskovski, 2013, The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality, Nature, 504, 456, 10.1038/nature12723 · DOI
  50. Bennett, 2010, Rescue of Drosophila melanogaster l(2)35Aa lethality is only mediated by polypeptide GalNAc-transferase pgant35A, but not by the evolutionary conserved human ortholog GalNAc-transferase-T11, Glycoconj. J, 27, 435, 10.1007/s10719-010-9290-5 · DOI
  51. Tian, 2007, A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is required for epithelial tube formation, J. Biol. Chem, 282, 606, 10.1074/jbc.M606268200 · DOI
  52. Parra-Peralbo, 2011, Drosophila lipophorin receptors mediate the uptake of neutral lipids in oocytes and imaginal disc cells by an endocytosis-independent mechanism, PLoS Genet, 7, e1001297, 10.1371/journal.pgen.1001297 · DOI
  53. Rodenburg, 2006, Sequence analysis of the non-recurring C-terminal domains shows that insect lipoprotein receptors constitute a distinct group of LDL receptor family members, Insect. Biochem. Mol. Biol, 36, 250, 10.1016/j.ibmb.2006.01.003 · DOI
  54. Fisher, 2006, Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors, Mol. Cell, 22, 277, 10.1016/j.molcel.2006.02.021 · DOI · Paper page
  55. Davignon, 2010, The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosis, Curr. Atheroscler. Rep, 12, 308, 10.1007/s11883-010-0123-6 · DOI
  56. Zhang, 2008, Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor, Proc. Natl. Acad. Sci. U.S.A, 105, 13045, 10.1073/pnas.0806312105 · DOI · Paper page
  57. Olofsson, 2005, Glycoconjugate glycans as viral receptors, Ann. Med, 37, 154, 10.1080/07853890510007340 · DOI
  58. Finkelshtein, 2013, LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus, Proc. Natl. Acad. Sci. U.S.A, 110, 7306, 10.1073/pnas.1214441110 · DOI · Paper page
  59. Molina, 2007, The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus, J. Hepatol, 46, 411, 10.1016/j.jhep.2006.09.024 · DOI

Cited by

Sorted by citations

Metadata

Authors
Pedersen, N. B., Wang, S., Narimatsu, Y., Yang, Z., Halim, A., Schjoldager, K. T.-B. G., Madsen, T. D., Seidah, N. G., Bennett, E. P., Levery, S. B., & Clausen, H.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2014-06
Volume
289
Issue
25
Pages
17312-17324
ISSN
0021-9258
DOI
10.1074/jbc.m113.545053
Cited by
66
References
3
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review