ID LARG1_HUMAN Reviewed; 756 AA. AC O95461; B0QXZ7; O60348; Q17R80; Q9UGD1; Q9UGE7; Q9UGG3; Q9UGZ8; Q9UH22; DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 27-MAR-2024, entry version 190. DE RecName: Full=Xylosyl- and glucuronyltransferase LARGE1 {ECO:0000305}; DE EC=2.4.-.- {ECO:0000269|PubMed:22223806}; DE AltName: Full=Acetylglucosaminyltransferase-like 1A; DE AltName: Full=Glycosyltransferase-like protein; DE AltName: Full=LARGE xylosyl- and glucuronyltransferase 1 {ECO:0000312|HGNC:HGNC:6511}; DE Includes: DE RecName: Full=Alpha-1,3-xylosyltransferase LARGE1 {ECO:0000305}; DE EC=2.4.2.- {ECO:0000269|PubMed:22223806}; DE Includes: DE RecName: Full=Beta-1,3-glucuronyltransferase LARGE1 {ECO:0000305}; DE EC=2.4.1.- {ECO:0000269|PubMed:22223806, ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699}; GN Name=LARGE1 {ECO:0000312|HGNC:HGNC:6511}; Synonyms=KIAA0609, LARGE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=9892679; DOI=10.1073/pnas.96.2.598; RA Peyrard M., Seroussi E., Sandberg-Nordqvist A.-C., Xie Y.-G., Han F.-Y., RA Fransson I., Collins J.E., Dunham I., Kost-Alimova M., Imreh S., RA Dumanski J.P.; RT "The human LARGE gene from 22q12.3-q13.1 is a new, distinct member of the RT glycosyltransferase gene family."; RL Proc. Natl. Acad. Sci. U.S.A. 96:598-603(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15752776; DOI=10.1016/j.bbrc.2005.02.082; RA Fujimura K., Sawaki H., Sakai T., Hiruma T., Nakanishi N., Sato T., RA Ohkura T., Narimatsu H.; RT "LARGE2 facilitates the maturation of alpha-dystroglycan more effectively RT than LARGE."; RL Biochem. Biophys. Res. Commun. 329:1162-1171(2005). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=15958417; DOI=10.1093/glycob/cwi094; RA Grewal P.K., McLaughlan J.M., Moore C.J., Browning C.A., Hewitt J.E.; RT "Characterization of the LARGE family of putative glycosyltransferases RT associated with dystroglycanopathies."; RL Glycobiology 15:912-923(2005). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 242-GLY--GLY-244; RP 334-GLY--GLY-336 AND 563-GLY--GLY-565. RX PubMed=15661757; DOI=10.1093/hmg/ddi062; RA Brockington M., Torelli S., Prandini P., Boito C., Dolatshad N.F., RA Longman C., Brown S.C., Muntoni F.; RT "Localization and functional analysis of the LARGE family of RT glycosyltransferases: significance for muscular dystrophy."; RL Hum. Mol. Genet. 14:657-665(2005). RN [9] RP INTERACTION WITH B4GAT1. RX PubMed=19587235; DOI=10.1073/pnas.0904515106; RA Bao X., Kobayashi M., Hatakeyama S., Angata K., Gullberg D., Nakayama J., RA Fukuda M.N., Fukuda M.; RT "Tumor suppressor function of laminin-binding alpha-dystroglycan requires a RT distinct beta3-N-acetylglucosaminyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 106:12109-12114(2009). RN [10] RP FUNCTION. RX PubMed=21987822; DOI=10.1073/pnas.1114836108; RA Hara Y., Kanagawa M., Kunz S., Yoshida-Moriguchi T., Satz J.S., RA Kobayashi Y.M., Zhu Z., Burden S.J., Oldstone M.B., Campbell K.P.; RT "Like-acetylglucosaminyltransferase (LARGE)-dependent modification of RT dystroglycan at Thr-317/319 is required for laminin binding and arenavirus RT infection."; RL Proc. Natl. Acad. Sci. U.S.A. 108:17426-17431(2011). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 242-ASP--ASP-244 AND RP 563-ASP--ASP-565. RX PubMed=22223806; DOI=10.1126/science.1214115; RA Inamori K., Yoshida-Moriguchi T., Hara Y., Anderson M.E., Yu L., RA Campbell K.P.; RT "Dystroglycan function requires xylosyl- and glucuronyltransferase RT activities of LARGE."; RL Science 335:93-96(2012). RN [12] RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=23125099; DOI=10.1093/glycob/cws152; RA Inamori K., Hara Y., Willer T., Anderson M.E., Zhu Z., RA Yoshida-Moriguchi T., Campbell K.P.; RT "Xylosyl- and glucuronyltransferase functions of LARGE in alpha- RT dystroglycan modification are conserved in LARGE2."; RL Glycobiology 23:295-302(2013). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND PATHWAY. RX PubMed=25279699; DOI=10.7554/elife.03941; RA Willer T., Inamori K.I., Venzke D., Harvey C., Morgensen G., Hara Y., RA Beltran Valero de Bernabe D., Yu L., Wright K.M., Campbell K.P.; RT "The glucuronyltransferase B4GAT1 is required for initiation of LARGE- RT mediated alpha-dystroglycan functional glycosylation."; RL Elife 3:0-0(2014). RN [14] RP FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY. RX PubMed=25279697; DOI=10.7554/elife.03943; RA Praissman J.L., Live D.H., Wang S., Ramiah A., Chinoy Z.S., Boons G.J., RA Moremen K.W., Wells L.; RT "B4GAT1 is the priming enzyme for the LARGE-dependent functional RT glycosylation of alpha-dystroglycan."; RL Elife 3:0-0(2014). RN [15] RP FUNCTION, COFACTOR, AND CATALYTIC ACTIVITY. RX PubMed=25138275; DOI=10.1074/jbc.m114.597831; RA Inamori K., Willer T., Hara Y., Venzke D., Anderson M.E., Clarke N.F., RA Guicheney P., Bonnemann C.G., Moore S.A., Campbell K.P.; RT "Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for RT functional modification of alpha-dystroglycan in cells and tissues."; RL J. Biol. Chem. 289:28138-28148(2014). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32975514; DOI=10.7554/elife.61388; RA Walimbe A.S., Okuma H., Joseph S., Yang T., Yonekawa T., Hord J.M., RA Venzke D., Anderson M.E., Torelli S., Manzur A., Devereaux M., Cuellar M., RA Prouty S., Ocampo Landa S., Yu L., Xiao J., Dixon J.E., Muntoni F., RA Campbell K.P.; RT "POMK regulates dystroglycan function via LARGE1-mediated elongation of RT matriglycan."; RL Elife 9:0-0(2020). RN [17] RP VARIANT MDDGB6 LYS-509. RX PubMed=12966029; DOI=10.1093/hmg/ddg307; RA Longman C., Brockington M., Torelli S., Jimenez-Mallebrera C., Kennedy C., RA Khalil N., Feng L., Saran R.K., Voit T., Merlini L., Sewry C.A., RA Brown S.C., Muntoni F.; RT "Mutations in the human LARGE gene cause MDC1D, a novel form of congenital RT muscular dystrophy with severe mental retardation and abnormal RT glycosylation of alpha-dystroglycan."; RL Hum. Mol. Genet. 12:2853-2861(2003). RN [18] RP VARIANT MDDGA6 PHE-331. RX PubMed=19067344; DOI=10.1002/ana.21482; RA Clement E., Mercuri E., Godfrey C., Smith J., Robb S., Kinali M., RA Straub V., Bushby K., Manzur A., Talim B., Cowan F., Quinlivan R., RA Klein A., Longman C., McWilliam R., Topaloglu H., Mein R., Abbs S., RA North K., Barkovich A.J., Rutherford M., Muntoni F.; RT "Brain involvement in muscular dystrophies with defective dystroglycan RT glycosylation."; RL Ann. Neurol. 64:573-582(2008). RN [19] RP VARIANT MDDGA6 ARG-495. RX PubMed=19299310; DOI=10.1212/01.wnl.0000346518.68110.60; RA Mercuri E., Messina S., Bruno C., Mora M., Pegoraro E., Comi G.P., RA D'Amico A., Aiello C., Biancheri R., Berardinelli A., Boffi P., RA Cassandrini D., Laverda A., Moggio M., Morandi L., Moroni I., Pane M., RA Pezzani R., Pichiecchio A., Pini A., Minetti C., Mongini T., Mottarelli E., RA Ricci E., Ruggieri A., Saredi S., Scuderi C., Tessa A., Toscano A., RA Tortorella G., Trevisan C.P., Uggetti C., Vasco G., Santorelli F.M., RA Bertini E.; RT "Congenital muscular dystrophies with defective glycosylation of RT dystroglycan: a population study."; RL Neurology 72:1802-1809(2009). RN [20] RP VARIANT MDDGA6 TYR-443. RX PubMed=24709677; DOI=10.1097/nen.0000000000000065; RA Meilleur K.G., Zukosky K., Medne L., Fequiere P., Powell-Hamilton N., RA Winder T.L., Alsaman A., El-Hattab A.W., Dastgir J., Hu Y., Donkervoort S., RA Golden J.A., Eagle R., Finkel R., Scavina M., Hood I.C., Rorke-Adams L.B., RA Boennemann C.G.; RT "Clinical, pathologic, and mutational spectrum of dystroglycanopathy caused RT by LARGE mutations."; RL J. Neuropathol. Exp. Neurol. 73:425-441(2014). CC -!- FUNCTION: Bifunctional glycosyltransferase with both alpha-1,3- CC xylosyltransferase and beta-1,3-glucuronyltransferase activities CC involved in the maturation of alpha-dystroglycan (DAG1) by CC glycosylation leading to DAG1 binding to laminin G-like domain- CC containing extracellular proteins with high affinity (PubMed:22223806, CC PubMed:15752776, PubMed:15661757, PubMed:25279699, PubMed:25279697, CC PubMed:23125099, PubMed:21987822). Elongates the glucuronyl-beta-1,4- CC xylose-beta disaccharide primer structure initiated by B4GAT1 by adding CC repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a CC heteropolysaccharide (PubMed:22223806, PubMed:25279699, CC PubMed:25279697, PubMed:25138275, PubMed:32975514, PubMed:23125099). CC Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by CC POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide CC primer (PubMed:21987822). Plays a key role in skeletal muscle function CC and regeneration (By similarity). {ECO:0000250|UniProtKB:Q9Z1M7, CC ECO:0000269|PubMed:15661757, ECO:0000269|PubMed:15752776, CC ECO:0000269|PubMed:21987822, ECO:0000269|PubMed:22223806, CC ECO:0000269|PubMed:23125099, ECO:0000269|PubMed:25138275, CC ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699, CC ECO:0000269|PubMed:32975514}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-[beta-D-GlcA-(1->3)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3- CC beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr- CC [protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-Xyl-(1->3)-beta-D-GlcA- CC (1->4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)- CC beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + H(+) + UDP; CC Xref=Rhea:RHEA:57336, Rhea:RHEA-COMP:17482, Rhea:RHEA-COMP:17483, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57632, ChEBI:CHEBI:58223, CC ChEBI:CHEBI:177336, ChEBI:CHEBI:177352; CC Evidence={ECO:0000269|PubMed:22223806, ECO:0000269|PubMed:23125099, CC ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57337; CC Evidence={ECO:0000305|PubMed:22223806, ECO:0000305|PubMed:25279697, CC ECO:0000305|PubMed:25279699}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-{(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->](n)-4)-beta- CC D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc- CC (1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-alpha-D-glucuronate = CC 3-O-{beta-D-GlcA-(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->](n)-4)- CC beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D- CC GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + H(+) + UDP; CC Xref=Rhea:RHEA:67924, Rhea:RHEA-COMP:17484, Rhea:RHEA-COMP:17486, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, CC ChEBI:CHEBI:177354, ChEBI:CHEBI:177355; CC Evidence={ECO:0000269|PubMed:22223806, ECO:0000269|PubMed:23125099, CC ECO:0000269|PubMed:25138275, ECO:0000269|PubMed:25279697, CC ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:32975514}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67925; CC Evidence={ECO:0000305|PubMed:22223806, ECO:0000305|PubMed:25138275, CC ECO:0000305|PubMed:25279697, ECO:0000305|PubMed:25279699, CC ECO:0000305|PubMed:32975514}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-{beta-D-GlcA-(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA- CC (1->](n)-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc- CC (1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP- CC alpha-D-xylose = 3-O-{(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA- CC (1->](n+1)-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc- CC (1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + H(+) CC + UDP; Xref=Rhea:RHEA:68368, Rhea:RHEA-COMP:17485, Rhea:RHEA- CC COMP:17486, ChEBI:CHEBI:15378, ChEBI:CHEBI:57632, ChEBI:CHEBI:58223, CC ChEBI:CHEBI:177354, ChEBI:CHEBI:177355; CC Evidence={ECO:0000269|PubMed:22223806, ECO:0000269|PubMed:25279697, CC ECO:0000269|PubMed:25279699}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68369; CC Evidence={ECO:0000305|PubMed:22223806, ECO:0000305|PubMed:25279697, CC ECO:0000305|PubMed:25279699}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:25138275}; CC Note=Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds CC one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one CC Mn(2+). {ECO:0000269|PubMed:25138275}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 5 for xylosyltransferase activity. Optimum pH is from CC 5.5 to 8.0 for Beta-1,3-glucuronyltransferase activity. CC {ECO:0000269|PubMed:23125099}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699}. CC -!- SUBUNIT: Interacts with DAG1 (via the N-terminal domain of alpha-DAG1); CC the interaction increases binding of DAG1 to laminin (By similarity). CC Interacts with B4GAT1 (PubMed:19587235). {ECO:0000250|UniProtKB:Q9Z1M7, CC ECO:0000269|PubMed:19587235}. CC -!- INTERACTION: CC O95461-1; O43505: B4GAT1; NbExp=2; IntAct=EBI-15792998, EBI-6138697; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000269|PubMed:15661757, ECO:0000269|PubMed:15958417, CC ECO:0000269|PubMed:25279699}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:15661757, ECO:0000269|PubMed:15958417}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95461-1; Sequence=Displayed; CC Name=2; CC IsoId=O95461-2; Sequence=VSP_014536; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in heart, brain and CC skeletal muscle. {ECO:0000269|PubMed:15752776}. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with impaired CC intellectual development B6 (MDDGB6) [MIM:608840]: A congenital CC muscular dystrophy associated with profound intellectual disability, CC white matter changes and structural brain abnormalities. Skeletal CC muscle biopsies show reduced immunolabeling of alpha-dystroglycan. CC {ECO:0000269|PubMed:12966029}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain CC and eye anomalies A6 (MDDGA6) [MIM:613154]: An autosomal recessive CC disorder characterized by congenital muscular dystrophy associated with CC cobblestone lissencephaly and other brain anomalies, eye malformations, CC profound intellectual disability, and death usually in the first years CC of life. Included diseases are the more severe Walker-Warburg syndrome CC and the slightly less severe muscle-eye-brain disease. CC {ECO:0000269|PubMed:19067344, ECO:0000269|PubMed:19299310, CC ECO:0000269|PubMed:24709677}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC glycosyltransferase 49 family. {ECO:0000305}. CC -!- SIMILARITY: In the N-terminal section; belongs to the CC glycosyltransferase 8 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA25535.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; CC Note=Glycosyltransferase-like protein LARGE1; CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_549"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ007583; CAA07571.1; -; mRNA. DR EMBL; AB011181; BAA25535.3; ALT_INIT; mRNA. DR EMBL; CR456510; CAG30396.1; -; mRNA. DR EMBL; AL008630; CAI17950.1; -; Genomic_DNA. DR EMBL; AL008715; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI17950.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI17890.1; -; Genomic_DNA. DR EMBL; AL008630; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI17890.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI18784.1; -; Genomic_DNA. DR EMBL; AL008630; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI18784.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI18785.1; -; Genomic_DNA. DR EMBL; AL008630; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI18785.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI18772.1; -; Genomic_DNA. DR EMBL; AL008630; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI18772.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI18788.1; -; Genomic_DNA. DR EMBL; AL008630; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI18788.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI18769.1; -; Genomic_DNA. DR EMBL; AL008630; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI18769.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAI18754.1; -; Genomic_DNA. DR EMBL; AL008630; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAI18754.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ06856.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ06856.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ08281.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ08281.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ08801.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ08801.1; JOINED; Genomic_DNA. DR EMBL; AL008630; CAQ09323.1; -; Genomic_DNA. DR EMBL; AL008715; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ09323.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ09434.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ09434.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ09895.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ09895.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ10763.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ10763.1; JOINED; Genomic_DNA. DR EMBL; Z70288; CAQ11002.1; -; Genomic_DNA. DR EMBL; AL008630; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; AL008715; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; AL096754; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; Z68287; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; Z69042; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; Z69943; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; Z82173; CAQ11002.1; JOINED; Genomic_DNA. DR EMBL; BC117425; AAI17426.1; -; mRNA. DR EMBL; BC126404; AAI26405.1; -; mRNA. DR CCDS; CCDS13912.1; -. [O95461-1] DR CCDS; CCDS93153.1; -. [O95461-2] DR PIR; T00256; T00256. DR RefSeq; NP_004728.1; NM_004737.5. [O95461-1] DR RefSeq; NP_598397.1; NM_133642.3. [O95461-1] DR RefSeq; XP_005261888.1; XM_005261831.3. DR RefSeq; XP_005261889.1; XM_005261832.3. DR RefSeq; XP_011528812.1; XM_011530510.2. DR PDB; 7UI6; EM; 3.70 A; A/B=34-756. DR PDB; 7UI7; EM; 3.40 A; A/B=34-756. DR PDB; 7ZVJ; X-ray; 2.61 A; A/B=134-752. DR PDBsum; 7UI6; -. DR PDBsum; 7UI7; -. DR PDBsum; 7ZVJ; -. DR AlphaFoldDB; O95461; -. DR EMDB; EMD-14985; -. DR EMDB; EMD-14987; -. DR SMR; O95461; -. DR BioGRID; 114649; 23. DR DIP; DIP-48922N; -. DR IntAct; O95461; 7. DR STRING; 9606.ENSP00000347088; -. DR BindingDB; O95461; -. DR ChEMBL; CHEMBL2146300; -. DR CAZy; GT49; Glycosyltransferase Family 49. DR CAZy; GT8; Glycosyltransferase Family 8. DR GlyCosmos; O95461; 4 sites, No reported glycans. DR GlyGen; O95461; 4 sites. DR iPTMnet; O95461; -. DR PhosphoSitePlus; O95461; -. DR SwissPalm; O95461; -. DR BioMuta; LARGE1; -. DR EPD; O95461; -. DR jPOST; O95461; -. DR MassIVE; O95461; -. DR MaxQB; O95461; -. DR PaxDb; 9606-ENSP00000347088; -. DR PeptideAtlas; O95461; -. DR ProteomicsDB; 50896; -. [O95461-1] DR ProteomicsDB; 50897; -. [O95461-2] DR Antibodypedia; 25305; 175 antibodies from 29 providers. DR DNASU; 9215; -. DR Ensembl; ENST00000354992.7; ENSP00000347088.2; ENSG00000133424.22. [O95461-1] DR Ensembl; ENST00000397394.8; ENSP00000380549.2; ENSG00000133424.22. [O95461-1] DR Ensembl; ENST00000402320.6; ENSP00000385223.1; ENSG00000133424.22. [O95461-2] DR Ensembl; ENST00000413114.6; ENSP00000415546.2; ENSG00000133424.22. [O95461-1] DR Ensembl; ENST00000675416.1; ENSP00000502826.1; ENSG00000133424.22. [O95461-1] DR Ensembl; ENST00000676070.1; ENSP00000502152.1; ENSG00000133424.22. [O95461-1] DR Ensembl; ENST00000676132.1; ENSP00000501854.1; ENSG00000133424.22. [O95461-1] DR Ensembl; ENST00000676370.1; ENSP00000502238.1; ENSG00000133424.22. [O95461-1] DR GeneID; 9215; -. DR KEGG; hsa:9215; -. DR MANE-Select; ENST00000397394.8; ENSP00000380549.2; NM_133642.5; NP_598397.1. DR UCSC; uc010gwp.4; human. [O95461-1] DR AGR; HGNC:6511; -. DR CTD; 9215; -. DR DisGeNET; 9215; -. DR GeneCards; LARGE1; -. DR HGNC; HGNC:6511; LARGE1. DR HPA; ENSG00000133424; Low tissue specificity. DR MalaCards; LARGE1; -. DR MIM; 603590; gene. DR MIM; 608840; phenotype. DR MIM; 613154; phenotype. DR neXtProt; NX_O95461; -. DR OpenTargets; ENSG00000133424; -. DR Orphanet; 370968; Congenital muscular dystrophy with intellectual disability. DR Orphanet; 588; Muscle-eye-brain disease. DR Orphanet; 899; Walker-Warburg syndrome. DR PharmGKB; PA30296; -. DR VEuPathDB; HostDB:ENSG00000133424; -. DR eggNOG; KOG3765; Eukaryota. DR GeneTree; ENSGT00940000158497; -. DR HOGENOM; CLU_019238_3_2_1; -. DR InParanoid; O95461; -. DR OMA; GWNKVSY; -. DR OrthoDB; 1363389at2759; -. DR PhylomeDB; O95461; -. DR TreeFam; TF319168; -. DR BioCyc; MetaCyc:ENSG00000133424-MONOMER; -. DR BRENDA; 2.4.1.B80; 2681. DR BRENDA; 2.4.2.B18; 2681. DR PathwayCommons; O95461; -. DR Reactome; R-HSA-5083627; Defective LARGE causes MDDGA6 and MDDGB6. DR Reactome; R-HSA-5173105; O-linked glycosylation. DR SignaLink; O95461; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 9215; 12 hits in 1144 CRISPR screens. DR ChiTaRS; LARGE1; human. DR GeneWiki; LARGE; -. DR GenomeRNAi; 9215; -. DR Pharos; O95461; Tbio. DR PRO; PR:O95461; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; O95461; Protein. DR Bgee; ENSG00000133424; Expressed in heart left ventricle and 164 other cell types or tissues. DR ExpressionAtlas; O95461; baseline and differential. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; TAS:UniProtKB. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl. DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; TAS:ProtInc. DR GO; GO:0015020; F:glucuronosyltransferase activity; IDA:UniProtKB. DR GO; GO:0016757; F:glycosyltransferase activity; TAS:UniProtKB. DR GO; GO:0016758; F:hexosyltransferase activity; IDA:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB. DR GO; GO:0035252; F:UDP-xylosyltransferase activity; TAS:Reactome. DR GO; GO:0042285; F:xylosyltransferase activity; IDA:UniProtKB. DR GO; GO:0095500; P:acetylcholine receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl. DR GO; GO:0071711; P:basement membrane organization; IEA:Ensembl. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl. DR GO; GO:0060348; P:bone development; IEA:Ensembl. DR GO; GO:0055013; P:cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0061448; P:connective tissue development; IEA:Ensembl. DR GO; GO:0007010; P:cytoskeleton organization; IEA:Ensembl. DR GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0009101; P:glycoprotein biosynthetic process; TAS:UniProtKB. DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; TAS:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl. DR GO; GO:0051674; P:localization of cell; IEA:Ensembl. DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0032504; P:multicellular organism reproduction; IEA:Ensembl. DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISS:UniProtKB. DR GO; GO:0042552; P:myelination; IEA:Ensembl. DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; TAS:ProtInc. DR GO; GO:0021675; P:nerve development; IEA:Ensembl. DR GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl. DR GO; GO:0007274; P:neuromuscular synaptic transmission; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0007009; P:plasma membrane organization; IEA:Ensembl. DR GO; GO:0035129; P:post-embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0043687; P:post-translational protein modification; IEA:Ensembl. DR GO; GO:0071805; P:potassium ion transmembrane transport; IEA:Ensembl. DR GO; GO:0021740; P:principal sensory nucleus of trigeminal nerve development; IEA:Ensembl. DR GO; GO:0006486; P:protein glycosylation; IMP:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0006493; P:protein O-linked glycosylation; TAS:Reactome. DR GO; GO:0035269; P:protein O-linked mannosylation; IDA:UniProtKB. DR GO; GO:0006612; P:protein targeting to membrane; IEA:Ensembl. DR GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl. DR GO; GO:0150103; P:reactive gliosis; IEA:Ensembl. DR GO; GO:0009416; P:response to light stimulus; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0010842; P:retina layer formation; IEA:Ensembl. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl. DR GO; GO:0098528; P:skeletal muscle fiber differentiation; IEA:Ensembl. DR GO; GO:0060538; P:skeletal muscle organ development; ISS:UniProtKB. DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISS:UniProtKB. DR GO; GO:0055002; P:striated muscle cell development; IEA:Ensembl. DR GO; GO:0006941; P:striated muscle contraction; IEA:Ensembl. DR GO; GO:0051124; P:synaptic assembly at neuromuscular junction; IEA:Ensembl. DR GO; GO:0090659; P:walking behavior; IEA:Ensembl. DR GO; GO:0006833; P:water transport; IEA:Ensembl. DR CDD; cd06431; GT8_LARGE_C; 1. DR InterPro; IPR002495; Glyco_trans_8. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR PANTHER; PTHR12270; GLYCOSYLTRANSFERASE-RELATED; 1. DR PANTHER; PTHR12270:SF48; XYLOSYL- AND GLUCURONYLTRANSFERASE LARGE1; 1. DR Pfam; PF13896; Glyco_transf_49; 1. DR Pfam; PF01501; Glyco_transf_8; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. DR Genevisible; O95461; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; KW Congenital muscular dystrophy; Disease variant; Dystroglycanopathy; KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Lissencephaly; KW Manganese; Membrane; Metal-binding; Multifunctional enzyme; KW Reference proteome; Signal-anchor; Transferase; Transmembrane; KW Transmembrane helix. FT CHAIN 1..756 FT /note="Xylosyl- and glucuronyltransferase LARGE1" FT /id="PRO_0000206060" FT TOPO_DOM 1..10 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 11..31 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 32..756 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 43..69 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 81..109 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 138..413 FT /note="Xylosyltransferase activity" FT /evidence="ECO:0000305|PubMed:22223806" FT REGION 414..756 FT /note="Glucuronyltransferase activity" FT /evidence="ECO:0000305|PubMed:22223806" FT COILED 53..95 FT /evidence="ECO:0000255" FT BINDING 242 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000305, ECO:0000305|PubMed:25138275" FT BINDING 244 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000305, ECO:0000305|PubMed:25138275" FT BINDING 563 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000305, ECO:0000305|PubMed:25138275" FT BINDING 565 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000305, ECO:0000305|PubMed:25138275" FT CARBOHYD 97 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 122 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 148 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 378..429 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9628581" FT /id="VSP_014536" FT VARIANT 68 FT /note="R -> G (in dbSNP:rs470035)" FT /id="VAR_013685" FT VARIANT 68 FT /note="R -> P (in dbSNP:rs135311)" FT /id="VAR_013686" FT VARIANT 331 FT /note="S -> F (in MDDGA6; dbSNP:rs267607210)" FT /evidence="ECO:0000269|PubMed:19067344" FT /id="VAR_065064" FT VARIANT 443 FT /note="C -> Y (in MDDGA6)" FT /evidence="ECO:0000269|PubMed:24709677" FT /id="VAR_075304" FT VARIANT 495 FT /note="W -> R (in MDDGA6; dbSNP:rs267607209)" FT /evidence="ECO:0000269|PubMed:19299310" FT /id="VAR_065065" FT VARIANT 509 FT /note="E -> K (in MDDGB6; dbSNP:rs121908675)" FT /evidence="ECO:0000269|PubMed:12966029" FT /id="VAR_019811" FT VARIANT 665 FT /note="R -> H (in dbSNP:rs1046166)" FT /id="VAR_013687" FT MUTAGEN 242..244 FT /note="DTD->NNN: Loss of function, but does not abolish FT subcellular location." FT /evidence="ECO:0000269|PubMed:15661757" FT MUTAGEN 242..244 FT /note="DTD->NTN: Glucuronyltransferase activity is present FT while xylosyltransferase activity is abolished." FT /evidence="ECO:0000269|PubMed:22223806" FT MUTAGEN 334..336 FT /note="DQD->NNN: Loss of function, but does not abolish FT subcellular location." FT /evidence="ECO:0000269|PubMed:15661757" FT MUTAGEN 563..565 FT /note="DID->NIN: Xylosyltransferase activity is present FT while glucuronyltransferase activity is abolished." FT /evidence="ECO:0000269|PubMed:22223806" FT MUTAGEN 563..565 FT /note="DID->NNN: Loss of function and abolishes subcellular FT location." FT /evidence="ECO:0000269|PubMed:15661757" FT STRAND 138..144 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 147..163 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 168..174 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 176..189 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 194..201 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 202..207 FT /evidence="ECO:0007829|PDB:7ZVJ" FT TURN 208..210 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 213..215 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 218..222 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 223..226 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 227..230 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 237..241 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 245..247 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 251..257 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 258..260 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 267..271 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 276..278 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 295..303 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 304..309 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 312..326 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 327..332 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 334..344 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 346..348 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 349..352 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 354..356 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 357..359 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 394..405 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 409..413 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 426..436 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 444..450 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 474..481 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 482..486 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 487..494 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 499..505 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 507..518 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 521..525 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 528..535 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 538..540 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 543..552 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 555..561 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 566..568 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 572..582 FT /evidence="ECO:0007829|PDB:7ZVJ" FT TURN 583..587 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 590..593 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 596..599 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 610..618 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 621..624 FT /evidence="ECO:0007829|PDB:7ZVJ" FT TURN 626..629 FT /evidence="ECO:0007829|PDB:7ZVJ" FT TURN 632..634 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 639..644 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 649..651 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 661..664 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 676..679 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 680..690 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:7ZVJ" FT STRAND 703..705 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 713..716 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 721..741 FT /evidence="ECO:0007829|PDB:7ZVJ" FT HELIX 744..750 FT /evidence="ECO:0007829|PDB:7ZVJ" SQ SEQUENCE 756 AA; 88066 MW; B022E118379AA17C CRC64; MLGICRGRRK FLAASLSLLC IPAITWIYLF SGSFEDGKPV SLSPLESQAH SPRYTASSQR ERESLEVRMR EVEEENRALR RQLSLAQGRA PSHRRGNHSK TYSMEEGTGD SENLRAGIVA GNSSECGQQP VVEKCETIHV AIVCAGYNAS RDVVTLVKSV LFHRRNPLHF HLIADSIAEQ ILATLFQTWM VPAVRVDFYN ADELKSEVSW IPNKHYSGIY GLMKLVLTKT LPANLERVIV LDTDITFATD IAELWAVFHK FKGQQVLGLV ENQSDWYLGN LWKNHRPWPA LGRGYNTGVI LLLLDKLRKM KWEQMWRLTA ERELMGMLST SLADQDIFNA VIKQNPFLVY QLPCFWNVQL SDHTRSEQCY RDVSDLKVIH WNSPKKLRVK NKHVEFFRNL YLTFLEYDGN LLRRELFGCP SEADVNSENL QKQLSELDED DLCYEFRRER FTVHRTHLYF LHYEYEPAAD STDVTLVAQL SMDRLQMLEA ICKHWEGPIS LALYLSDAEA QQFLRYAQGS EVLMSRHNVG YHIVYKEGQF YPVNLLRNVA MKHISTPYMF LSDIDFLPMY GLYEYLRKSV IQLDLANTKK AMIVPAFETL RYRLSFPKSK AELLSMLDMG TLFTFRYHVW TKGHAPTNFA KWRTATTPYR VEWEADFEPY VVVRRDCPEY DRRFVGFGWN KVAHIMELDV QEYEFIVLPN AYMIHMPHAP SFDITKFRSN KQYRICLKTL KEEFQQDMSR RYGFAALKYL TAENNS //