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O94766 (B3GA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3

EC=2.4.1.135
Alternative name(s):
Beta-1,3-glucuronyltransferase 3
Glucuronosyltransferase I
Short name=GlcAT-I
UDP-GlcUA:Gal beta-1,3-Gal-R glucuronyltransferase
Short name=GlcUAT-I
Gene names
Name:B3GAT3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length335 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Glycosaminoglycans biosynthesis. Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal-beta-1,3-Gal-beta-1,4-Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. Can also play a role in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. Shows strict specificity for Gal-beta-1,3-Gal-beta-1,4-Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Gal beta1-O-benzyl, Galbeta1-4GlcNAc and Galbeta1-4Glc.

Catalytic activity

UDP-glucuronate + 3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D-xylosylprotein = UDP + 3-beta-D-glucuronosyl-3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D-xylosylprotein.

Cofactor

Manganese.

Enzyme regulation

Inhibited by EDTA.

Pathway

Protein modification; protein glycosylation.

Subunit structure

Homodimer; disulfide-linked.

Subcellular location

Golgi apparatus membrane; Single-pass type II membrane protein. Golgi apparatuscis-Golgi network Ref.6.

Tissue specificity

Ubiquitous (but weakly expressed in all tissues examined).

Post-translational modification

N-glycosylated.

Involvement in disease

Multiple joint dislocations short stature craniofacial dysmorphism and congenital heart defects (JDSSDHD) [MIM:245600]: An autosomal recessive disease characterized by dysmorphic facies, bilateral dislocations of the elbows, hips, and knees, clubfeet, and short stature, as well as cardiovascular defects.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the glycosyltransferase 43 family.

Ontologies

Keywords
   Cellular componentGolgi apparatus
Membrane
   DiseaseDisease mutation
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandManganese
Metal-binding
   Molecular functionTransferase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

chondroitin sulfate metabolic process

Traceable author statement. Source: Reactome

chondroitin sulfate proteoglycan biosynthetic process

Inferred from direct assay Ref.6. Source: MGI

dermatan sulfate proteoglycan biosynthetic process

Inferred from direct assay Ref.6. Source: MGI

glycosaminoglycan biosynthetic process

Non-traceable author statement Ref.2. Source: UniProtKB

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

heparan sulfate proteoglycan biosynthetic process

Inferred from direct assay Ref.6. Source: MGI

protein glycosylation

Inferred from electronic annotation. Source: UniProtKB-UniPathway

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.6. Source: MGI

Golgi membrane

Traceable author statement. Source: Reactome

cis-Golgi network

Inferred from direct assay Ref.6. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

integral component of membrane

Non-traceable author statement Ref.2. Source: UniProtKB

   Molecular_functiongalactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity

Non-traceable author statement Ref.2. Source: UniProtKB

glucuronosyltransferase activity

Inferred from mutant phenotype Ref.6. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 335335Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3
PRO_0000195176

Regions

Topological domain1 – 77Cytoplasmic Potential
Transmembrane8 – 2821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain29 – 335307Lumenal Potential
Nucleotide binding82 – 843UDP-glucuronate binding
Nucleotide binding194 – 1963UDP-glucuronate binding
Nucleotide binding308 – 3103UDP-glucuronate binding
Region243 – 25210Interaction with galactose moiety of substrate glycoprotein

Sites

Active site2811Proton donor/acceptor Ref.9
Metal binding1961Manganese
Binding site1131UDP-glucuronate
Binding site1561UDP-glucuronate
Binding site1611UDP-glucuronate
Site2271Interaction with galactose moiety of substrate glycoprotein
Site3181Interaction with galactose moiety of substrate glycoprotein

Amino acid modifications

Glycosylation3001N-linked (GlcNAc...)
Disulfide bond33Interchain

Natural variations

Natural variant2771R → Q in JDSSDHD; reduced activity; patient fibroblasts have decreased levels of dermatan sulfate, chondroitin sulfate and heparan sulfate proteoglycans. Ref.6
VAR_066624

Experimental info

Mutagenesis331C → A: Loss of dimer formation and reduced activity.
Mutagenesis3011C → A: Enzyme inactivation and loss of glycosylation.
Sequence conflict2041F → S in BAA34537. Ref.1

Secondary structure

........................................... 335
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O94766 [UniParc].

Last modified April 26, 2004. Version 2.
Checksum: 5EC45408597F1C0F

FASTA33537,122
        10         20         30         40         50         60 
MKLKLKNVFL AYFLVSIAGL LYALVQLGQP CDCLPPLRAA AEQLRQKDLR ISQLQAELRR 

        70         80         90        100        110        120 
PPPAPAQPPE PEALPTIYVV TPTYARLVQK AELVRLSQTL SLVPRLHWLL VEDAEGPTPL 

       130        140        150        160        170        180 
VSGLLAASGL LFTHLVVLTP KAQRLREGEP GWVHPRGVEQ RNKALDWLRG RGGAVGGEKD 

       190        200        210        220        230        240 
PPPPGTQGVV YFADDDNTYS RELFEEMRWT RGVSVWPVGL VGGLRFEGPQ VQDGRVVGFH 

       250        260        270        280        290        300 
TAWEPSRPFP VDMAGFAVAL PLLLDKPNAQ FDSTAPRGHL ESSLLSHLVD PKDLEPRAAN 

       310        320        330 
CTRVLVWHTR TEKPKMKQEE QLQRQGRGSD PAIEV 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans."
Kitagawa H., Tone Y., Tamura J., Neumann K.W., Ogawa T., Oka S., Kawasaki T., Sugahara K.
J. Biol. Chem. 273:6615-6618(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Tissue: Placenta.
[2]"Structure/function of the human Ga1beta1,3-glucuronosyltransferase. Dimerization and functional activity are mediated by two crucial cysteine residues."
Ouzzine M., Gulberti S., Netter P., Magdalou J., Fournel-Gigleux S.
J. Biol. Chem. 275:28254-28260(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, MUTAGENESIS.
[3]"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].
Tissue: Eye and Skin.
[4]"Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway."
Herman T., Horvitz H.R.
Proc. Natl. Acad. Sci. U.S.A. 96:974-979(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-335.
Tissue: Brain.
[5]"Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans."
Tone Y., Kitagawa H., Imiya K., Oka S., Kawasaki T., Sugahara K.
FEBS Lett. 459:415-420(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[6]"Faulty initiation of proteoglycan synthesis causes cardiac and joint defects."
Baasanjav S., Al-Gazali L., Hashiguchi T., Mizumoto S., Fischer B., Horn D., Seelow D., Ali B.R., Aziz S.A., Langer R., Saleh A.A., Becker C., Nurnberg G., Cantagrel V., Gleeson J.G., Gomez D., Michel J.B., Stricker S. expand/collapse author list , Lindner T.H., Nurnberg P., Sugahara K., Mundlos S., Hoffmann K.
Am. J. Hum. Genet. 89:15-27(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, VARIANT JDSSDHD GLN-277, CHARACTERIZATION OF VARIANT JDSSDHD GLN-277.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I."
Pedersen L.C., Tsuchida K., Kitagawa H., Sugahara K., Darden T.A., Negishi M.
J. Biol. Chem. 275:34580-34585(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 76-335 IN COMPLEX WITH UDP-GLUCURONIC ACID AND GALACTOSE MOIETY OF SUBSTRATE GLYCOPROTEIN.
Tissue: Liver.
[9]"Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA."
Pedersen L.C., Darden T.A., Negishi M.
J. Biol. Chem. 277:21869-21873(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 76-335 IN COMPLEX WITH UDP-GLUCURONIC ACID, ACTIVE SITE.
[10]"2-o-phosphorylation of xylose and 6-O-sulfation of galactose in the protein linkage region of glycosaminoglycans influence the glucuronyltransferase-I activity involved in the linkage region synthesis."
Tone Y., Pedersen L.C., Yamamoto T., Izumikawa T., Kitagawa H., Nishihara J., Tamura J., Negishi M., Sugahara K.
J. Biol. Chem. 283:16801-16807(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 76-335 IN COMPLEX WITH URIDINE-5'-DIPHOSPHATE AND GALACTOSE MOIETY OF SUBSTRATE GLYCOPROTEIN.
+Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB009598 mRNA. Translation: BAA34537.1.
BC007906 mRNA. Translation: AAH07906.1.
BC071961 mRNA. Translation: AAH71961.1.
AJ005865 mRNA. Translation: CAA06742.1.
RefSeqNP_036332.2. NM_012200.3.
UniGeneHs.502759.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FGGX-ray2.30A/B76-335[»]
1KWSX-ray2.10A/B76-335[»]
3CU0X-ray1.90A/B76-335[»]
ProteinModelPortalO94766.
SMRO94766. Positions 76-335.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117620. 3 interactions.
IntActO94766. 1 interaction.
STRING9606.ENSP00000265471.

Protein family/group databases

CAZyGT43. Glycosyltransferase Family 43.

PTM databases

PhosphoSiteO94766.

Proteomic databases

PaxDbO94766.
PRIDEO94766.

Protocols and materials databases

DNASU26229.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265471; ENSP00000265471; ENSG00000149541.
GeneID26229.
KEGGhsa:26229.
UCSCuc001ntw.3. human.

Organism-specific databases

CTD26229.
GeneCardsGC11M062429.
HGNCHGNC:923. B3GAT3.
HPAHPA051328.
MIM245600. phenotype.
606374. gene.
neXtProtNX_O94766.
Orphanet284139. Larsen-like syndrome, B3GAT3 type.
PharmGKBPA25217.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310844.
HOVERGENHBG050650.
InParanoidO94766.
KOK10158.
OMAFPMDMAG.
OrthoDBEOG7QG44X.
PhylomeDBO94766.
TreeFamTF313522.

Enzyme and pathway databases

BioCycMetaCyc:HS07624-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00378.

Gene expression databases

ArrayExpressO94766.
BgeeO94766.
CleanExHS_B3GAT3.
GenevestigatorO94766.

Family and domain databases

InterProIPR005027. Glyco_trans_43.
[Graphical view]
PANTHERPTHR10896. PTHR10896. 1 hit.
PfamPF03360. Glyco_transf_43. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSB3GAT3. human.
EvolutionaryTraceO94766.
GeneWikiB3GAT3.
GenomeRNAi26229.
NextBio48391.
PROO94766.
SOURCESearch...

Entry information

Entry nameB3GA3_HUMAN
AccessionPrimary (citable) accession number: O94766
Secondary accession number(s): Q96I06, Q9UEP0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: April 26, 2004
Last modified: April 16, 2014
This is version 139 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 11

Human chromosome 11: entries, gene names and cross-references to MIM