LARGE1

Summary

Gene Symbol: LARGE1
Description: LARGE xylosyl- and glucuronyltransferase 1
Alias: LARGE, MDC1D, MDDGA6, MDDGB6, LARGE xylosyl- and glucuronyltransferase 1, acetylglucosaminyltransferase-like 1A, acetylglucosaminyltransferase-like protein, glycosyltransferase-like protein LARGE1
Species: human
Products:     LARGE1

Top Publications

  1. Michele D, Barresi R, Kanagawa M, Saito F, Cohn R, Satz J, et al. Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies. Nature. 2002;418:417-22 pubmed
  2. Inamori K, Yoshida Moriguchi T, Hara Y, Anderson M, Yu L, Campbell K. Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science. 2012;335:93-6 pubmed publisher
    Posttranslational modification of alpha-dystroglycan (?-DG) by the like-acetylglucosaminyltransferase (LARGE) is required for it to function as an extracellular matrix (ECM) receptor...
  3. Fujimura K, Sawaki H, Sakai T, Hiruma T, Nakanishi N, Sato T, et al. LARGE2 facilitates the maturation of alpha-dystroglycan more effectively than LARGE. Biochem Biophys Res Commun. 2005;329:1162-71 pubmed
    The LARGE gene is thought to encode a putative glycosyltransferase because of its typical topology...
  4. Brockington M, Torelli S, Prandini P, Boito C, Dolatshad N, Longman C, et al. Localization and functional analysis of the LARGE family of glycosyltransferases: significance for muscular dystrophy. Hum Mol Genet. 2005;14:657-65 pubmed
    ..The LARGE glycosyltransferase is mutated in both the myodystrophy mouse and congenital muscular dystrophy type 1D (MDC1D)...
  5. Barresi R, Michele D, Kanagawa M, Harper H, Dovico S, Satz J, et al. LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nat Med. 2004;10:696-703 pubmed
    ..putative glycosyltransferase mutated both in Large(myd) mice and in humans with congenital muscular dystrophy 1D (MDC1D)...
  6. Kanagawa M, Saito F, Kunz S, Yoshida Moriguchi T, Barresi R, Kobayashi Y, et al. Molecular recognition by LARGE is essential for expression of functional dystroglycan. Cell. 2004;117:953-64 pubmed
    ..Posttranslational modification of alpha-dystroglycan by glycosyltransferase, LARGE, occurs within the mucin-like domain, but the N-terminal domain interacts with LARGE, defining an intracellular ..
  7. Peyrard M, Seroussi E, Sandberg Nordqvist A, Xie Y, Han F, Fransson I, et al. The human LARGE gene from 22q12.3-q13.1 is a new, distinct member of the glycosyltransferase gene family. Proc Natl Acad Sci U S A. 1999;96:598-603 pubmed
    ..We characterized a new member of the N-acetylglucosaminyltransferase gene family, the LARGE gene. It occupies >664 kilobases and is one of the largest human genes...
  8. Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B, et al. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain. 2007;130:2725-35 pubmed
    ..define the mutation frequency and phenotypes associated with mutations in the other five genes, we studied a large cohort of patients with evidence of a dystroglycanopathy...
  9. Longman C, Brockington M, Torelli S, Jimenez Mallebrera C, Kennedy C, Khalil N, et al. Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Hum Mol Genet. 2003;12:2853-61 pubmed
    ..Another putative glycosyltransferase, Large, is mutated in the myodystrophy mouse...

More Information

Publications28

  1. Grewal P, McLaughlan J, Moore C, Browning C, Hewitt J. Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies. Glycobiology. 2005;15:912-23 pubmed
    ..We suggest that vertebrate LARGE orthologs be referred to as LARGE1. RT-PCR, dot-blot, and northern analysis indicated that LARGE2 has a more restricted tissue-expression profile ..
  2. Hara Y, Kanagawa M, Kunz S, Yoshida Moriguchi T, Satz J, Kobayashi Y, et al. Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection. Proc Natl Acad Sci U S A. 2011;108:17426-31 pubmed publisher
    ..Like-acetylglucosaminyltransferase (LARGE) is a key molecule that binds to the N-terminal domain of ?-dystroglycan and attaches ligand-binding moieties to ..
  3. Praissman J, Live D, Wang S, Ramiah A, Chinoy Z, Boons G, et al. B4GAT1 is the priming enzyme for the LARGE-dependent functional glycosylation of α-dystroglycan. elife. 2014;3: pubmed publisher
    ..The dual-activity LARGE enzyme is capable of extending products of B4GAT1 and we provide experimental evidence that B4GAT1 is the priming ..
  4. Inamori K, Willer T, Hara Y, Venzke D, Anderson M, Clarke N, et al. Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of ?-dystroglycan in cells and tissues. J Biol Chem. 2014;289:28138-48 pubmed publisher
    Mutations in the LARGE gene have been identified in congenital muscular dystrophy (CMD) patients with brain abnormalities...
  5. Kapoor M, Wang J, Wetherill L, Le N, Bertelsen S, Hinrichs A, et al. Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families. Drug Alcohol Depend. 2014;142:56-62 pubmed publisher
    ..The present study evaluated whether single nucleotide polymorphisms (SNPs) can influence the age at onset of AD in large high-risk families from the Collaborative Study on the Genetics of Alcoholism (COGA)...
  6. Mercuri E, Messina S, Bruno C, Mora M, Pegoraro E, Comi G, et al. Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. Neurology. 2009;72:1802-9 pubmed publisher
    ..study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and alpha-DG reduction on muscle biopsy (n = 76) or with a phenotype ..
  7. Meilleur K, Zukosky K, Medne L, Fequiere P, Powell Hamilton N, Winder T, et al. Clinical, pathologic, and mutational spectrum of dystroglycanopathy caused by LARGE mutations. J Neuropathol Exp Neurol. 2014;73:425-41 pubmed publisher
    ..dystroglycanopathy genes affect a specific glycoepitope on α-dystroglycan; of the 14 genes implicated to date, LARGE encodes the glycosyltransferase that adds the final xylose and glucuronic acid, allowing α-dystroglycan to bind ..
  8. Gao G, Johnson S, Vasmatzis G, Pauley C, Tombers N, Kasperbauer J, et al. Common fragile sites (CFS) and extremely large CFS genes are targets for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma. Genes Chromosomes Cancer. 2017;56:59-74 pubmed publisher
    ..1Mb), LRP1B (1.9Mb), and LARGE1 (0.7Mb)...
  9. de la Morena Barrio M, Buil A, Antón A, Martínez Martínez I, Minano A, Gutiérrez Gallego R, et al. Identification of antithrombin-modulating genes. Role of LARGE, a gene encoding a bifunctional glycosyltransferase, in the secretion of proteins?. PLoS ONE. 2013;8:e64998 pubmed publisher
    ..This validation study suggested LARGE, a gene encoding a protein with xylosyltransferase and glucuronyltransferase activities that forms heparin-like ..
  10. Vuillaumier Barrot S, Bouchet Seraphin C, Chelbi M, Eude Caye A, Charluteau E, Besson C, et al. Intragenic rearrangements in LARGE and POMGNT1 genes in severe dystroglycanopathies. Neuromuscul Disord. 2011;21:782-90 pubmed publisher
    ..To date, six distinct genes, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE and recently in one case DPM3, have been shown to be involved in dystroglycanopathies...
  11. Goddeeris M, Wu B, Venzke D, Yoshida Moriguchi T, Saito F, Matsumura K, et al. LARGE glycans on dystroglycan function as a tunable matrix scaffold to prevent dystrophy. Nature. 2013;503:136-40 pubmed publisher
    ..of the polysaccharide repeating unit [-3-xylose-?1,3-glucuronic acid-?1-]n by like-acetylglucosaminyltransferase (LARGE) is required for the glycoprotein dystroglycan to function as a receptor for proteins in the extracellular matrix...
  12. He J, Kelly T, Zhao Q, Li H, Huang J, Wang L, et al. Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese. Circ Cardiovasc Genet. 2013;6:598-607 pubmed publisher
    ..Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline. ..
  13. Clarke N, Maugenre S, Vandebrouck A, Urtizberea J, Willer T, Peat R, et al. Congenital muscular dystrophy type 1D (MDC1D) due to a large intragenic insertion/deletion, involving intron 10 of the LARGE gene. Eur J Hum Genet. 2011;19:452-7 pubmed publisher
    ..We report further a family with MDC1D due to a complex genomic rearrangement that was not apparent on standard sequencing of LARGE...
  14. Zhang H, Xia X, Zhu F, Shen H, Song K, Shang Z. Correlation of deregulated like-acetylglucosaminyl transferase and aberrant ?-dystroglycan expression with human tongue cancer metastasis. J Oral Maxillofac Surg. 2014;72:1106-18 pubmed publisher
    ..study examined the correlation of ?-dystroglycan (?-DG) expression and like-acetylglucosaminyl transferase (LARGE) with metastasis of human tongue cancer...
  15. de Bernabe D, Inamori K, Yoshida Moriguchi T, Weydert C, Harper H, Willer T, et al. Loss of alpha-dystroglycan laminin binding in epithelium-derived cancers is caused by silencing of LARGE. J Biol Chem. 2009;284:11279-84 pubmed publisher
    ..cell membrane but lacks laminin binding as a result of the silencing of the like-acetylglucosaminyltransferase (LARGE) gene in a cohort of highly metastatic epithelial cell lines derived from breast, cervical, and lung cancers...
  16. Willer T, Inamori K, Venzke D, Harvey C, Morgensen G, Hara Y, et al. The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated α-dystroglycan functional glycosylation. elife. 2014;3: pubmed publisher
    ..acid β1,4-xylose disaccharide synthesized by B4GAT1 acts as an acceptor primer that can be elongated by LARGE with the ligand-binding heteropolysaccharide...
  17. van Reeuwijk J, Grewal P, Salih M, Beltran Valero de Bernabe D, McLaughlan J, Michielse C, et al. Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome. Hum Genet. 2007;121:685-90 pubmed
    Intragenic homozygous deletions in the Large gene are associated with a severe neuromuscular phenotype in the myodystrophy (myd) mouse. These mutations result in a virtual lack of glycosylation of alpha-dystroglycan...
  18. Brockington M, Torelli S, Sharp P, Liu K, Cirak S, Brown S, et al. Transgenic overexpression of LARGE induces α-dystroglycan hyperglycosylation in skeletal and cardiac muscle. PLoS ONE. 2010;5:e14434 pubmed publisher
    b>LARGE is one of seven putative or demonstrated glycosyltransferase enzymes defective in a common group of muscular dystrophies with reduced glycosylation of α-dystroglycan...