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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in B3GAT3 are the cause of 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. 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	glycosaminoglycan biosynthetic process Non-traceable author statement Ref.2. Source: UniProtKB
Cellular component	Golgi membrane Non-traceable author statement. 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

Sites

Active site

281

1

Proton acceptor

Metal binding

196

1

Manganese

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 – 112

10

Beta strand

114 – 116

3

Helix

119 – 128

10

Beta strand

131 – 136

6

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 – 264

5

Helix

280 – 285

6

Turn

286 – 288

3

Helix

291 – 293

3

Helix

298 – 301

4

Helix

317 – 324

8

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: 9506957] [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: 10842173] [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: 15489334] [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: 9927678] [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: 10526176] [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: 21763480] [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: 21269460] [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: 10946001] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 76-335. Tissue: Liver.
+	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.

SMR

O94766. Positions 76-335.

ModBase

Search...

Protein-protein interaction databases

IntAct

O94766. 1 interaction.

STRING

O94766.

Protein family/group databases

CAZy

GT43. Glycosyltransferase Family 43.

PTM databases

PhosphoSite

O94766.

Proteomic databases

PRIDE

O94766.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265471; ENSP00000265471; ENSG00000149541.

GeneID

26229.

KEGG

hsa:26229.

UCSC

uc001ntw.1. human.

Organism-specific databases

CTD

26229.

GeneCards

GC11M062429.

H-InvDB

HIX0009715.

HGNC

HGNC:923. B3GAT3.

MIM

245600. phenotype.
606374. gene.

neXtProt

NX_O94766.

PharmGKB

PA25217.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13338.

HOVERGEN

HBG050650.

InParanoid

O94766.

OMA

EMRWTRG.

OrthoDB

EOG42NJ0R.

PhylomeDB

O94766.

Enzyme and pathway databases

BioCyc

MetaCyc:HS07624-MONOMER.

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]

KO

K10158.

PANTHER

PTHR10896. Glyco_trans_43. 1 hit.

Pfam

PF03360. Glyco_transf_43. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

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:	January 25, 2012
This is version 117 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.