O94766 (B3GA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	335 AA.
Sequence status	Complete.
Protein existence	Evidence 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 apparatus › cis-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 component	Golgi apparatus Membrane
Disease	Disease mutation
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Manganese Metal-binding
Molecular function	Transferase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate 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 heparan sulfate proteoglycan biosynthetic process Inferred from direct assay Ref.6. Source: MGI protein glycosylation Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	Golgi membrane Non-traceable author statement. Source: UniProtKB cis-Golgi network Inferred from direct assay Ref.6. Source: UniProtKB integral to membrane Non-traceable author statement Ref.2. Source: UniProtKB
Molecular_function	galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity Non-traceable author statement Ref.2. Source: UniProtKB manganese ion binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 335

335

Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3

PRO_0000195176

Regions

Topological domain

1 – 7

7

Cytoplasmic Potential

Transmembrane

8 – 28

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

29 – 335

307

Lumenal Potential

Nucleotide binding

82 – 84

3

UDP-glucuronate binding

Nucleotide binding

194 – 196

3

UDP-glucuronate binding

Nucleotide binding

308 – 310

3

UDP-glucuronate binding

Region

243 – 252

10

Interaction with galactose moiety of substrate glycoprotein

Sites

Active site

281

1

Proton donor/acceptor Ref.9

Metal binding

196

1

Manganese

Binding site

113

1

UDP-glucuronate

Binding site

156

1

UDP-glucuronate

Binding site

161

1

UDP-glucuronate

Site

227

1

Interaction with galactose moiety of substrate glycoprotein

Site

318

1

Interaction with galactose moiety of substrate glycoprotein

Amino acid modifications

Glycosylation

300

1

N-linked (GlcNAc...)

Disulfide bond

33

Interchain

Natural variations

Natural variant

277

1

R → 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

Mutagenesis

33

1

C → A: Loss of dimer formation and reduced activity.

Mutagenesis

301

1

C → A: Enzyme inactivation and loss of glycosylation.

Sequence conflict

204

1

F → S in BAA34537. Ref.1

Secondary structure

1

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335

Helix Strand Turn

Details...

Beta strand

76 – 83

8

Helix

89 – 100

12

Beta strand

103 – 116

14

Helix

119 – 128

10

Beta strand

130 – 136

7

Helix

158 – 168

11

Beta strand

174 – 177

4

Beta strand

188 – 192

5

Beta strand

197 – 199

3

Helix

201 – 207

7

Beta strand

211 – 215

5

Beta strand

218 – 221

4

Beta strand

224 – 232

9

Beta strand

235 – 240

6

Helix

253 – 255

3

Beta strand

256 – 259

4

Helix

260 – 265

6

Helix

280 – 285

6

Turn

286 – 288

3

Helix

291 – 293

3

Helix

298 – 301

4

Helix

317 – 323

7

Turn

324 – 326

3

Sequences

	Sequence		Length	Mass (Da)
	O94766 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: 5EC45408597F1C0F	FASTA	335	37,122
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00304331.

RefSeq

NP_036332.2. NM_012200.3.

UniGene

Hs.502759.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FGG	X-ray	2.30	A/B	76-335	[»]
1KWS	X-ray	2.10	A/B	76-335	[»]
3CU0	X-ray	1.90	A/B	76-335	[»]

ProteinModelPortal

O94766.

ModBase

Search...

Protein-protein interaction databases

IntAct

O94766. 1 interaction.

STRING

9606.ENSP00000265471.

Protein family/group databases

CAZy

GT43. Glycosyltransferase Family 43.

PTM databases

PhosphoSite

O94766.

Proteomic databases

PaxDb

O94766.

PRIDE

O94766.

Protocols and materials databases

DNASU

26229.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265471; ENSP00000265471; ENSG00000149541.

GeneID

26229.

KEGG

hsa:26229.

UCSC

uc001ntw.3. human.

Organism-specific databases

CTD

26229.

GeneCards

GC11M062429.

HGNC

HGNC:923. B3GAT3.

MIM

245600. phenotype.
606374. gene.

neXtProt

NX_O94766.

Orphanet

284139. Larsen-like syndrome, B3GAT3 type.

PharmGKB

PA25217.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG310844.

HOVERGEN

HBG050650.

InParanoid

O94766.

KO

K10158.

OMA

FHTAWEP.

OrthoDB

EOG42NJ0R.

PhylomeDB

O94766.

Enzyme and pathway databases

BioCyc

MetaCyc:HS07624-MONOMER.

Reactome

REACT_111217. Metabolism.
REACT_116125. Disease.

UniPathway

UPA00378.

Gene expression databases

ArrayExpress

O94766.

Bgee

O94766.

CleanEx

HS_B3GAT3.

Genevestigator

O94766.

GermOnline

ENSG00000149541. Homo sapiens.

Family and domain databases

InterPro

IPR005027. Glyco_trans_43.
[Graphical view]

PANTHER

PTHR10896. PTHR10896. 1 hit.

Pfam

PF03360. Glyco_transf_43. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL3958.

ChiTaRS

B3GAT3. human.

EvolutionaryTrace

O94766.

GenomeRNAi

26229.

NextBio

48391.

SOURCE

Search...

Entry information

Entry name

B3GA3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.