Reviewed, UniProtKB/Swiss-Prot O95461 (LARGE_HUMAN)

Names and origin

Protein names

Recommended name:
    Glycosyltransferase-like protein LARGE1
    EC=2.4.-.-
Alternative name(s):
    Acetylglucosaminyltransferase-like 1A

Gene names

Name:	LARGE
Synonyms:	KIAA0609, LARGE1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Glycosyltransferase which participates in glycosylation of alpha-dystroglycan. May carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. May be involved in the addition of a repeated disaccharide unit.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein.
Tissue specificity	Ubiquitous. Highest expression in heart, brain and skeletal muscle.
Involvement in disease	Defects in LARGE are the cause of congenital muscular dystrophy type 1D (MDC1D) [MIM:608840]. The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessive disorders presenting in infancy with muscle weakness, contractures, and dystrophic changes on skeletal muscle biopsy. Structural brain defects, with or without mental retardation, are additional features of several CMD syndromes. MDC1D presented with congenital muscular dystrophy, profound mental retardation, and white matter changes and subtle structural abnormalities on brain MRI. Patient skeletal muscle biopsy showed reduced immunolabeling of alpha-dystroglycan.
Sequence similarities	Belongs to the glycosyltransferase 8 family.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital muscular dystrophy Disease mutation
Domain	Coiled coil Signal-anchor Transmembrane
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	N-acetylglucosamine metabolic process Ref.1 Traceable author statement. Source: ProtInc glycosphingolipid biosynthetic process Ref.1 Traceable author statement. Source: UniProtKB muscle maintenance Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid glycosylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to Golgi membrane Ref.1 Traceable author statement. Source: UniProtKB
Molecular function	acetylglucosaminyltransferase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95461-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95461-2)

The sequence of this isoform differs from the canonical sequence as follows:
     378-429: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 756	756	Glycosyltransferase-like protein LARGE1		PRO_0000206060
Regions
	Topological domain	1 – 10	10	Cytoplasmic Potential
	Transmembrane	11 – 31	21	Signal-anchor for type II membrane protein Potential
	Topological domain	32 – 756	725	Lumenal Potential
	Coiled coil	53 – 95	43	Potential
Amino acid modifications
	Glycosylation	97	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	148	1	N-linked (GlcNAc...) Potential
	Glycosylation	272	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	378 – 429	52	Missing in isoform 2.		VSP_014536
	Natural variant	68	1	R → G: dbSNP rs470035.		VAR_013685
	Natural variant	68	1	R → P: dbSNP rs135311.		VAR_013686
	Natural variant	509	1	E → K in MDC1D.		VAR_019811
	Natural variant	665	1	R → H: dbSNP rs1046166.		VAR_013687
Experimental info
	Mutagenesis	242 – 244	3	DTD → NNN: Loss of function, but does not abolish subcellular location
	Mutagenesis	334 – 336	3	DQD → NNN: Loss of function, but does not abolish subcellular location
	Mutagenesis	563 – 565	3	DID → NNN: Loss of function and abolishes subcellular location

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: B022E118379AA17C	FASTA	756	88,066
	10 20 30 40 50 60 MLGICRGRRK FLAASLSLLC IPAITWIYLF SGSFEDGKPV SLSPLESQAH SPRYTASSQR 70 80 90 100 110 120 ERESLEVRMR EVEEENRALR RQLSLAQGRA PSHRRGNHSK TYSMEEGTGD SENLRAGIVA 130 140 150 160 170 180 GNSSECGQQP VVEKCETIHV AIVCAGYNAS RDVVTLVKSV LFHRRNPLHF HLIADSIAEQ 190 200 210 220 230 240 ILATLFQTWM VPAVRVDFYN ADELKSEVSW IPNKHYSGIY GLMKLVLTKT LPANLERVIV 250 260 270 280 290 300 LDTDITFATD IAELWAVFHK FKGQQVLGLV ENQSDWYLGN LWKNHRPWPA LGRGYNTGVI 310 320 330 340 350 360 LLLLDKLRKM KWEQMWRLTA ERELMGMLST SLADQDIFNA VIKQNPFLVY QLPCFWNVQL 370 380 390 400 410 420 SDHTRSEQCY RDVSDLKVIH WNSPKKLRVK NKHVEFFRNL YLTFLEYDGN LLRRELFGCP 430 440 450 460 470 480 SEADVNSENL QKQLSELDED DLCYEFRRER FTVHRTHLYF LHYEYEPAAD STDVTLVAQL 490 500 510 520 530 540 SMDRLQMLEA ICKHWEGPIS LALYLSDAEA QQFLRYAQGS EVLMSRHNVG YHIVYKEGQF 550 560 570 580 590 600 YPVNLLRNVA MKHISTPYMF LSDIDFLPMY GLYEYLRKSV IQLDLANTKK AMIVPAFETL 610 620 630 640 650 660 RYRLSFPKSK AELLSMLDMG TLFTFRYHVW TKGHAPTNFA KWRTATTPYR VEWEADFEPY 670 680 690 700 710 720 VVVRRDCPEY DRRFVGFGWN KVAHIMELDV QEYEFIVLPN AYMIHMPHAP SFDITKFRSN 730 740 750 KQYRICLKTL KEEFQQDMSR RYGFAALKYL TAENNS
	Isoform 2 [UniParc]. Checksum: 9CCD42064004C7FF		704	81,846
	10 20 30 40 50 60 MLGICRGRRK FLAASLSLLC IPAITWIYLF SGSFEDGKPV SLSPLESQAH SPRYTASSQR 70 80 90 100 110 120 ERESLEVRMR EVEEENRALR RQLSLAQGRA PSHRRGNHSK TYSMEEGTGD SENLRAGIVA 130 140 150 160 170 180 GNSSECGQQP VVEKCETIHV AIVCAGYNAS RDVVTLVKSV LFHRRNPLHF HLIADSIAEQ 190 200 210 220 230 240 ILATLFQTWM VPAVRVDFYN ADELKSEVSW IPNKHYSGIY GLMKLVLTKT LPANLERVIV 250 260 270 280 290 300 LDTDITFATD IAELWAVFHK FKGQQVLGLV ENQSDWYLGN LWKNHRPWPA LGRGYNTGVI 310 320 330 340 350 360 LLLLDKLRKM KWEQMWRLTA ERELMGMLST SLADQDIFNA VIKQNPFLVY QLPCFWNVQL 370 380 390 400 410 420 SDHTRSEQCY RDVSDLKLQK QLSELDEDDL CYEFRRERFT VHRTHLYFLH YEYEPAADST 430 440 450 460 470 480 DVTLVAQLSM DRLQMLEAIC KHWEGPISLA LYLSDAEAQQ FLRYAQGSEV LMSRHNVGYH 490 500 510 520 530 540 IVYKEGQFYP VNLLRNVAMK HISTPYMFLS DIDFLPMYGL YEYLRKSVIQ LDLANTKKAM 550 560 570 580 590 600 IVPAFETLRY RLSFPKSKAE LLSMLDMGTL FTFRYHVWTK GHAPTNFAKW RTATTPYRVE 610 620 630 640 650 660 WEADFEPYVV VRRDCPEYDR RFVGFGWNKV AHIMELDVQE YEFIVLPNAY MIHMPHAPSF 670 680 690 700 DITKFRSNKQ YRICLKTLKE EFQQDMSRRY GFAALKYLTA ENNS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human LARGE gene from 22q12.3-q13.1 is a new, distinct member of the glycosyltransferase gene family." Peyrard M., Seroussi E., Sandberg-Nordqvist A.-C., Xie Y.-G., Han F.-Y., Fransson I., Collins J.E., Dunham I., Kost-Alimova M., Imreh S., Dumanski J.P. Proc. Natl. Acad. Sci. U.S.A. 96:598-603(1999) [PubMed: 9892679] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[6]	"LARGE2 facilitates the maturation of alpha-dystroglycan more effectively than LARGE." Fujimura K., Sawaki H., Sakai T., Hiruma T., Nakanishi N., Sato T., Ohkura T., Narimatsu H. Biochem. Biophys. Res. Commun. 329:1162-1171(2005) [PubMed: 15752776] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]	"Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies." Grewal P.K., McLaughlan J.M., Moore C.J., Browning C.A., Hewitt J.E. Glycobiology 15:912-923(2005) [PubMed: 15958417] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Localization and functional analysis of the LARGE family of glycosyltransferases: significance for muscular dystrophy." Brockington M., Torelli S., Prandini P., Boito C., Dolatshad N.F., Longman C., Brown S.C., Muntoni F. Hum. Mol. Genet. 14:657-665(2005) [PubMed: 15661757] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 242-GLY--GLY-244; 334-GLY--GLY-336 AND 563-GLY--GLY-565.
[9]	"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." Longman C., Brockington M., Torelli S., Jimenez-Mallebrera C., Kennedy C., Khalil N., Feng L., Saran R.K., Voit T., Merlini L., Sewry C.A., Brown S.C., Muntoni F. Hum. Mol. Genet. 12:2853-2861(2003) [PubMed: 12966029] [Abstract] Cited for: VARIANT MDC1D LYS-509.
+	Additional computationally mapped references.

Web resources

GeneReviews

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Glycosyltransferase-like protein LARGE1

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ007583 mRNA. Translation: CAA07571.1. AB011181 mRNA. Translation: BAA25535.3. Different initiation. CR456510 mRNA. Translation: CAG30396.1. AL008630 , AL008715, AL096754, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI17950.1. AL008715 , AL008630, AL096754, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI17890.1. AL096754 , AL008630, AL008715, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI18784.1. Z68287 , AL008630, AL008715, AL096754, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI18785.1. Z69042 , AL008630, AL008715, AL096754, Z68287, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI18772.1. Z69943 , AL008630, AL008715, AL096754, Z68287, Z69042, Z70288, Z82173 Genomic DNA. Translation: CAI18788.1. Z70288 , AL008630, AL008715, AL096754, Z68287, Z69042, Z69943, Z82173 Genomic DNA. Translation: CAI18769.1. Z82173 , AL008630, AL008715, AL096754, Z68287, Z69042, Z69943, Z70288 Genomic DNA. Translation: CAI18754.1. BC117425 mRNA. Translation: AAI17426.1. BC126404 mRNA. Translation: AAI26405.1.
PIR	T00256.
RefSeq	NP_004728.1. NP_598397.1.
UniGene	Hs.474667
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000133424. Homo sapiens. [Contig view]
GeneID	9215.
KEGG	hsa:9215.
Organism-specific databases
H-InvDB	HIX0016409.
HGNC	HGNC:6511. LARGE.
MIM	603590. gene. 608840. phenotype.
Orphanet	98894. Muscular dystrophy congenital, type 1d. 899. Walker-Warburg syndrome.
PharmGKB	PA30296.
HUGE	Search...
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	O95461.
Gene expression databases
ArrayExpress	O95461.
CleanEx	HS_LARGE.
GermOnline	ENSG00000133424. Homo sapiens.
Family and domain databases
InterPro	IPR002495. Glyco_trans_8. [Graphical view]
Pfam	PF01501. Glyco_transf_8. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	34547.
SOURCE	Search...

Entry information

Entry name

LARGE_HUMAN

Accession

Primary (citable) accession number: O95461
Secondary accession number(s): O60348 , Q17R80, Q9UGD1, Q9UGE7, Q9UGG3, Q9UGZ8, Q9UH22

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 26, 2002
Last sequence update:	May 1, 1999
Last modified:	November 4, 2008
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)