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Protein

Glycosyltransferase-like protein LARGE1

Gene

Large

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Bifunctional glycosyltransferase with both xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1) (PubMed:23125099, PubMed:23135544). Phosphorylated O-mannosyl trisaccharid is required for binding laminin G-like domain-containing extracellular proteins with high affinity and plays a key role in skeletal muscle function and regeneration (PubMed:15184894, PubMed:24132234). LARGE elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B3GNT1/B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (By similarity).By similarity5 Publications

Cofactori

Mn2+By similarityNote: Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn2+.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi242 – 2421Manganese 1By similarity
Metal bindingi244 – 2441Manganese 1By similarity
Metal bindingi563 – 5631Manganese 2By similarity
Metal bindingi565 – 5651Manganese 2By similarity

GO - Molecular functioni

  • glucuronosyltransferase activity Source: UniProtKB
  • manganese ion binding Source: UniProtKB
  • transferase activity, transferring glycosyl groups Source: UniProtKB
  • xylosyltransferase activity Source: UniProtKB

GO - Biological processi

  • glycoprotein biosynthetic process Source: UniProtKB
  • muscle cell cellular homeostasis Source: UniProtKB
  • protein O-linked mannosylation Source: UniProtKB
  • skeletal muscle organ development Source: UniProtKB
  • skeletal muscle tissue regeneration Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

UniPathwayiUPA00378.

Protein family/group databases

CAZyiGT49. Glycosyltransferase Family 49.
GT8. Glycosyltransferase Family 8.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycosyltransferase-like protein LARGE1 (EC:2.4.-.-)
Alternative name(s):
Acetylglucosaminyltransferase-like 1A
Including the following 2 domains:
Xylosyltransferase LARGECurated (EC:2.4.2.-By similarity)
Beta-1,3-glucuronyltransferase LARGECurated (EC:2.4.1.-By similarity)
Gene namesi
Name:Large
Synonyms:Kiaa0609, Large1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1342270. Large.

Subcellular locationi

  • Golgi apparatus membrane By similarity; Single-pass type II membrane protein By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1010CytoplasmicSequence Analysis
Transmembranei11 – 3121Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini32 – 756725LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Large are the cause of myodystrophy (myd), an autosomal recessive neuromuscular phenotype, probably due to abnormal post-translational modification of alpha-dystroglycan.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 756756Glycosyltransferase-like protein LARGE1PRO_0000206061Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi97 – 971N-linked (GlcNAc...)Sequence Analysis
Glycosylationi122 – 1221N-linked (GlcNAc...)Sequence Analysis
Glycosylationi148 – 1481N-linked (GlcNAc...)Sequence Analysis
Glycosylationi272 – 2721N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9Z1M7.
PaxDbiQ9Z1M7.
PRIDEiQ9Z1M7.

PTM databases

PhosphoSiteiQ9Z1M7.

Expressioni

Tissue specificityi

Ubiquitous. Highest expression in heart, diaphragm and brain, where it is especially found in cerebral cortex, hippocampus, and trigeminal ganglion.1 Publication

Developmental stagei

Ubiquitously found at 14.5 dpc with strong expression in heart, central nervous system structures such as cerebral cortex, hippocampus, olfactory lobe, trigeminal ganglion and spinal cord. Also expressed in diaphragm and duodenum.

Gene expression databases

BgeeiQ9Z1M7.
CleanExiMM_LARGE.
ExpressionAtlasiQ9Z1M7. baseline and differential.
GenevestigatoriQ9Z1M7.

Interactioni

Subunit structurei

Interacts with DAG1 (via the N-terminal domain of alpha-DAG1); the interaction increases binding of DAG1 to laminin. Interacts with B3GNT1/B4GAT1.By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000112617.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1M7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni138 – 413276Xylosyltransferase activityBy similarityAdd
BLAST
Regioni414 – 756343Glucuronyltransferase activityBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili53 – 9543Sequence AnalysisAdd
BLAST

Sequence similaritiesi

In the C-terminal section; belongs to the glycosyltransferase 49 family.Curated
In the N-terminal section; belongs to the glycosyltransferase 8 family.Curated

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG279004.
GeneTreeiENSGT00530000063165.
HOGENOMiHOG000231467.
HOVERGENiHBG052308.
InParanoidiQ9Z1M7.
KOiK09668.
OMAiFAALKYM.
OrthoDBiEOG7RJPQV.
PhylomeDBiQ9Z1M7.
TreeFamiTF319168.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR002495. Glyco_trans_8.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PfamiPF01501. Glyco_transf_8. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9Z1M7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGICRGRRK FLAASLTLLC IPAITWIYLF AGSFEDGKPV SLSPLESQAH
60 70 80 90 100
SPRYTASSQR ERESLEVRVR EVEEENRALR RQLSLAQGQS PAHHRGNHSK
110 120 130 140 150
TYSMEEGTGD SENLRAGIVA GNSSECGQQP AVEKCETIHV AIVCAGYNAS
160 170 180 190 200
RDVVTLVKSV LFHRRNPLHF HLIADSIAEQ ILATLFQTWM VPAVRVDFYN
210 220 230 240 250
ADELKSEVSW IPNKHYSGIY GLMKLVLTKT LPANLERVIV LDTDITFATD
260 270 280 290 300
IAELWAVFHK FKGQQVLGLV ENQSDWYLGN LWKNHRPWPA LGRGYNTGVI
310 320 330 340 350
LLLLDKLRKM KWEQMWRLTA ERELMGMLST SLADQDIFNA VIKQNPFLVY
360 370 380 390 400
QLPCFWNVQL SDHTRSEQCY RDVSDLKVIH WNSPKKLRVK NKHVEFFRNL
410 420 430 440 450
YLTFLEYDGN LLRRELFGCP SETDVNNENL QKQLSELDED DLCYEFRRER
460 470 480 490 500
FTVHRTHLYF LHYEFEPSAD NTDVTLVAQL SMDRLQMLEA ICKHWEGPIS
510 520 530 540 550
LALYLSDAEA QQFLRYAQGS EVLMSRQNVG YHIVYKEGQF YPVNLLRNVA
560 570 580 590 600
MKHISTPYMF LSDIDFLPMY GLYEYLRKSV IQLDLANTKK AMIVPAFETL
610 620 630 640 650
RYRLSFPKSK AELLSMLDMG TLFTFRYHVW TKGHAPTNFA KWRTATTPYQ
660 670 680 690 700
VEWEADFEPY VVVRRDCPEY DRRFVGFGWN KVAHIMELDA QEYEFTVLPN
710 720 730 740 750
AYMIHMPHAP SFDITKFRSN KQYRICLKTL KEEFQQDMSR RYGFAALKYL

TAENNS
Length:756
Mass (Da):87,964
Last modified:May 1, 1999 - v1
Checksum:i37B32E039AB8895F
GO

Sequence cautioni

The sequence AAH61506.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC65610.1 differs from that shown. Reason: Frameshift at position 48. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti269 – 2691L → S in AAI00400 (PubMed:12693553).Curated
Sequence conflicti324 – 3241L → H in AAI00400 (PubMed:12693553).Curated
Sequence conflicti441 – 4411D → N in AAI00400 (PubMed:12693553).Curated
Sequence conflicti748 – 7481K → E in AAI00400 (PubMed:12693553).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006278 mRNA. Translation: CAA06945.1.
AK122328 mRNA. Translation: BAC65610.1. Frameshift.
BC061506 mRNA. Translation: AAH61506.1. Different initiation.
BC100399 mRNA. Translation: AAI00400.1.
CCDSiCCDS22420.1.
RefSeqiNP_034817.1. NM_010687.1.
UniGeneiMm.324371.

Genome annotation databases

EnsembliENSMUST00000004497; ENSMUSP00000004497; ENSMUSG00000004383.
ENSMUST00000119826; ENSMUSP00000112617; ENSMUSG00000004383.
GeneIDi16795.
KEGGimmu:16795.
UCSCiuc009mgs.1. mouse.

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - GTase

Large like-glycosyltransferase

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006278 mRNA. Translation: CAA06945.1.
AK122328 mRNA. Translation: BAC65610.1. Frameshift.
BC061506 mRNA. Translation: AAH61506.1. Different initiation.
BC100399 mRNA. Translation: AAI00400.1.
CCDSiCCDS22420.1.
RefSeqiNP_034817.1. NM_010687.1.
UniGeneiMm.324371.

3D structure databases

ProteinModelPortaliQ9Z1M7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000112617.

Protein family/group databases

CAZyiGT49. Glycosyltransferase Family 49.
GT8. Glycosyltransferase Family 8.

PTM databases

PhosphoSiteiQ9Z1M7.

Proteomic databases

MaxQBiQ9Z1M7.
PaxDbiQ9Z1M7.
PRIDEiQ9Z1M7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004497; ENSMUSP00000004497; ENSMUSG00000004383.
ENSMUST00000119826; ENSMUSP00000112617; ENSMUSG00000004383.
GeneIDi16795.
KEGGimmu:16795.
UCSCiuc009mgs.1. mouse.

Organism-specific databases

CTDi9215.
MGIiMGI:1342270. Large.
RougeiSearch...

Phylogenomic databases

eggNOGiNOG279004.
GeneTreeiENSGT00530000063165.
HOGENOMiHOG000231467.
HOVERGENiHBG052308.
InParanoidiQ9Z1M7.
KOiK09668.
OMAiFAALKYM.
OrthoDBiEOG7RJPQV.
PhylomeDBiQ9Z1M7.
TreeFamiTF319168.

Enzyme and pathway databases

UniPathwayiUPA00378.

Miscellaneous databases

NextBioi290662.
PROiQ9Z1M7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Z1M7.
CleanExiMM_LARGE.
ExpressionAtlasiQ9Z1M7. baseline and differential.
GenevestigatoriQ9Z1M7.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR002495. Glyco_trans_8.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PfamiPF01501. Glyco_transf_8. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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].
    Tissue: Brain and Embryo.
  2. "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].
    Strain: FVB/N-3.
    Tissue: Embryonic stem cell and Mammary tumor.
  3. "Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
    DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse."
    Grewal P.K., Holzfeind P.J., Bittner R.E., Hewitt J.E.
    Nat. Genet. 28:151-154(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISEASE.
  5. Cited for: INTERACTION WITH DAG1.
  6. "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: TISSUE SPECIFICITY.
  7. Cited for: FUNCTION, PATHWAY.
  8. "Xylosyl- and glucuronyltransferase functions of LARGE in alpha-dystroglycan modification are conserved in LARGE2."
    Inamori K., Hara Y., Willer T., Anderson M.E., Zhu Z., Yoshida-Moriguchi T., Campbell K.P.
    Glycobiology 23:295-302(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "LARGE2 generates the same xylose- and glucuronic acid-containing glycan structures as LARGE."
    Ashikov A., Buettner F.F., Tiemann B., Gerardy-Schahn R., Bakker H.
    Glycobiology 23:303-309(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "LARGE glycans on dystroglycan function as a tunable matrix scaffold to prevent dystrophy."
    Goddeeris M.M., Wu B., Venzke D., Yoshida-Moriguchi T., Saito F., Matsumura K., Moore S.A., Campbell K.P.
    Nature 503:136-140(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PATHWAY.
  11. "Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of alpha-dystroglycan in cells and tissues."
    Inamori K., Willer T., Hara Y., Venzke D., Anderson M.E., Clarke N.F., Guicheney P., Bonnemann C.G., Moore S.A., Campbell K.P.
    J. Biol. Chem. 289:28138-28148(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiLARGE_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1M7
Secondary accession number(s): Q497S9, Q6P7U2, Q80TW0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 26, 2002
Last sequence update: May 1, 1999
Last modified: February 4, 2015
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.