LARG1_HUMAN
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 03-AUG-2022, entry version 181.
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";
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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 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 AlphaFoldDB; O95461; -.
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 GlyGen; O95461; 4 sites.
DR iPTMnet; O95461; -.
DR PhosphoSitePlus; O95461; -.
DR BioMuta; LARGE1; -.
DR EPD; O95461; -.
DR jPOST; O95461; -.
DR MassIVE; O95461; -.
DR MaxQB; O95461; -.
DR PaxDb; O95461; -.
DR PeptideAtlas; O95461; -.
DR PRIDE; O95461; -.
DR ProteomicsDB; 50896; -. [O95461-1]
DR ProteomicsDB; 50897; -. [O95461-2]
DR Antibodypedia; 25305; 169 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 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; WNIQLSD; -.
DR PhylomeDB; O95461; -.
DR TreeFam; TF319168; -.
DR BioCyc; MetaCyc:ENSG00000133424-MON; -.
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 1065 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 162 other tissues.
DR ExpressionAtlas; O95461; baseline and differential.
DR Genevisible; O95461; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030173; C:integral component of Golgi membrane; TAS:UniProtKB.
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:0009101; P:glycoprotein biosynthetic process; TAS:UniProtKB.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; TAS:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISS:UniProtKB.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; TAS:ProtInc.
DR GO; GO:0006486; P:protein glycosylation; IMP:UniProtKB.
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:0060538; P:skeletal muscle organ development; ISS:UniProtKB.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISS:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR002495; Glyco_trans_8.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF01501; Glyco_transf_8; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Congenital muscular dystrophy;
KW Disease variant; Dystroglycanopathy; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Lissencephaly; Manganese; Membrane; Metal-binding;
KW Multifunctional enzyme; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; 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"
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
