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O95461 (LARGE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycosyltransferase-like protein LARGE1

EC=2.4.-.-
Alternative name(s):
Acetylglucosaminyltransferase-like 1A
Gene names
Name:LARGE
Synonyms:KIAA0609, LARGE1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length756 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.6 Ref.8

Pathway

Protein modification; protein glycosylation.

Subunit structure

Interacts with DAG1 (via the N-terminal domain of alpha-DAG1); the interaction increases binding of DAG1 to laminin By similarity.

Subcellular location

Golgi apparatus membrane; Single-pass type II membrane protein Ref.7 Ref.8.

Tissue specificity

Ubiquitous. Highest expression in heart, brain and skeletal muscle. Ref.6

Involvement in disease

Muscular dystrophy-dystroglycanopathy congenital with mental retardation B6 (MDDGB6) [MIM:608840]: A congenital muscular dystrophy associated with profound mental retardation, white matter changes and structural brain abnormalities. Skeletal muscle biopsies show reduced immunolabeling of alpha-dystroglycan.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6 (MDDGA6) [MIM:613154]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the glycosyltransferase 8 family.

Sequence caution

The sequence BAA25535.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

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.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 756756Glycosyltransferase-like protein LARGE1
PRO_0000206060

Regions

Topological domain1 – 1010Cytoplasmic Potential
Transmembrane11 – 3121Helical; Signal-anchor for type II membrane protein; Potential
Topological domain32 – 756725Lumenal Potential
Coiled coil53 – 9543 Potential

Amino acid modifications

Glycosylation971N-linked (GlcNAc...) Potential
Glycosylation1221N-linked (GlcNAc...) Potential
Glycosylation1481N-linked (GlcNAc...) Potential
Glycosylation2721N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence378 – 42952Missing in isoform 2.
VSP_014536
Natural variant681R → G.
Corresponds to variant rs470035 [ dbSNP | Ensembl ].
VAR_013685
Natural variant681R → P.
Corresponds to variant rs135311 [ dbSNP | Ensembl ].
VAR_013686
Natural variant3311S → F in MDDGA6. Ref.10
VAR_065064
Natural variant4951W → R in MDDGA6. Ref.11
VAR_065065
Natural variant5091E → K in MDDGB6. Ref.9
VAR_019811
Natural variant6651R → H.
Corresponds to variant rs1046166 [ dbSNP | Ensembl ].
VAR_013687

Experimental info

Mutagenesis242 – 2443DTD → NNN: Loss of function, but does not abolish subcellular location.
Mutagenesis334 – 3363DQD → NNN: Loss of function, but does not abolish subcellular location. Ref.8
Mutagenesis563 – 5653DID → NNN: Loss of function and abolishes subcellular location. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: B022E118379AA17C

FASTA75688,066
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 9CCD42064004C7FF
Show »

FASTA70481,846

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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:R84.1-R84.11(2004) [PubMed] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT MDDGB6 LYS-509.
[10]"Brain involvement in muscular dystrophies with defective dystroglycan glycosylation."
Clement E., Mercuri E., Godfrey C., Smith J., Robb S., Kinali M., Straub V., Bushby K., Manzur A., Talim B., Cowan F., Quinlivan R., Klein A., Longman C., McWilliam R., Topaloglu H., Mein R., Abbs S. expand/collapse author list , North K., Barkovich A.J., Rutherford M., Muntoni F.
Ann. Neurol. 64:573-582(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MDDGA6 PHE-331.
[11]"Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study."
Mercuri E., Messina S., Bruno C., Mora M., Pegoraro E., Comi G.P., D'Amico A., Aiello C., Biancheri R., Berardinelli A., Boffi P., Cassandrini D., Laverda A., Moggio M., Morandi L., Moroni I., Pane M., Pezzani R. expand/collapse author list , Pichiecchio A., Pini A., Minetti C., Mongini T., Mottarelli E., Ricci E., Ruggieri A., Saredi S., Scuderi C., Tessa A., Toscano A., Tortorella G., Trevisan C.P., Uggetti C., Vasco G., Santorelli F.M., Bertini E.
Neurology 72:1802-1809(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MDDGA6 ARG-495.
+Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Glycosyltransferase-like protein LARGE1

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ007583 mRNA. Translation: CAA07571.1.
AB011181 mRNA. Translation: BAA25535.3. Different initiation.
CR456510 mRNA. Translation: CAG30396.1.
AL008630 expand/collapse EMBL AC list , AL008715, AL096754, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI17950.1.
AL008715 expand/collapse EMBL AC list , AL008630, AL096754, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI17890.1.
AL096754 expand/collapse EMBL AC list , AL008630, AL008715, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI18784.1.
Z68287 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI18785.1.
Z69042 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAI18772.1.
Z69943 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69042, Z70288, Z82173 Genomic DNA. Translation: CAI18788.1.
Z70288 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69042, Z69943, Z82173 Genomic DNA. Translation: CAI18769.1.
Z82173 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69042, Z69943, Z70288 Genomic DNA. Translation: CAI18754.1.
Z69943 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69042, Z70288, Z82173 Genomic DNA. Translation: CAQ06856.1.
AL096754 expand/collapse EMBL AC list , AL008630, AL008715, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAQ08281.1.
Z68287 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAQ08801.1.
AL008630 expand/collapse EMBL AC list , AL008715, AL096754, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAQ09323.1.
AL008715 expand/collapse EMBL AC list , AL008630, AL096754, Z68287, Z69042, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAQ09434.1.
Z82173 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69042, Z69943, Z70288 Genomic DNA. Translation: CAQ09895.1.
Z69042 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69943, Z70288, Z82173 Genomic DNA. Translation: CAQ10763.1.
Z70288 expand/collapse EMBL AC list , AL008630, AL008715, AL096754, Z68287, Z69042, Z69943, Z82173 Genomic DNA. Translation: CAQ11002.1.
BC117425 mRNA. Translation: AAI17426.1.
BC126404 mRNA. Translation: AAI26405.1.
CCDSCCDS13912.1. [O95461-1]
PIRT00256.
RefSeqNP_004728.1. NM_004737.4. [O95461-1]
NP_598397.1. NM_133642.3. [O95461-1]
XP_005261888.1. XM_005261831.1. [O95461-1]
XP_005261889.1. XM_005261832.1. [O95461-1]
UniGeneHs.474667.

3D structure databases

ProteinModelPortalO95461.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-48922N.
STRING9606.ENSP00000347088.

Chemistry

ChEMBLCHEMBL2146300.

Protein family/group databases

CAZyGT49. Glycosyltransferase Family 49.
GT8. Glycosyltransferase Family 8.

PTM databases

PhosphoSiteO95461.

Proteomic databases

MaxQBO95461.
PaxDbO95461.
PRIDEO95461.

Protocols and materials databases

DNASU9215.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000337431; ENSP00000336636; ENSG00000133424. [O95461-2]
ENST00000354992; ENSP00000347088; ENSG00000133424. [O95461-1]
ENST00000397394; ENSP00000380549; ENSG00000133424. [O95461-1]
ENST00000402320; ENSP00000385223; ENSG00000133424. [O95461-2]
GeneID9215.
KEGGhsa:9215.
UCSCuc003and.4. human. [O95461-1]
uc010gwp.3. human. [O95461-2]

Organism-specific databases

CTD9215.
GeneCardsGC22M033668.
GeneReviewsLARGE.
HGNCHGNC:6511. LARGE.
HPAHPA028878.
MIM603590. gene.
608840. phenotype.
613154. phenotype.
neXtProtNX_O95461.
Orphanet370968. Congenital muscular dystrophy with intellectual disability.
588. Muscle-eye-brain disease.
899. Walker-Warburg syndrome.
PharmGKBPA30296.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG279004.
HOVERGENHBG052308.
InParanoidO95461.
KOK09668.
OMALESQPHS.
OrthoDBEOG7RJPQV.
PhylomeDBO95461.
TreeFamTF319168.

Enzyme and pathway databases

UniPathwayUPA00378.

Gene expression databases

ArrayExpressO95461.
BgeeO95461.
CleanExHS_LARGE.
GenevestigatorO95461.

Family and domain databases

Gene3D3.90.550.10. 1 hit.
InterProIPR002495. Glyco_trans_8.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PfamPF01501. Glyco_transf_8. 1 hit.
[Graphical view]
SUPFAMSSF53448. SSF53448. 1 hit.
ProtoNetSearch...

Other

ChiTaRSLARGE. human.
GeneWikiLARGE.
GenomeRNAi9215.
NextBio34547.
PROO95461.
SOURCESearch...

Entry information

Entry nameLARGE_HUMAN
AccessionPrimary (citable) accession number: O95461
Secondary accession number(s): B0QXZ7 expand/collapse secondary AC list , 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: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM