Reviewed, UniProtKB/Swiss-Prot P15291 (B4GT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Beta-1,4-galactosyltransferase 1
      Short name=Beta-1,4-GalTase 1
      Short name=Beta4Gal-T1
      Short name=b4Gal-T1
    EC=2.4.1.-
Alternative name(s):
    UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 1
    UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 1
Cleaved into the following chain:
    1- Recommended name:
            Processed beta-1,4-galactosyltransferase 1
Including the following 4 domains:
    1- Recommended name:
            Lactose synthase A protein
              EC=2.4.1.22
    2- Recommended name:
            N-acetyllactosamine synthase
              EC=2.4.1.90
        Alternative name(s):
            Nal synthetase
    3- Recommended name:
            Beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase
              EC=2.4.1.38
    4- Recommended name:
            Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase
              EC=2.4.1.-

Gene names

Name:	B4GALT1
Synonyms:	GGTB2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	398 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The Golgi complex form catalyzes the production of lactose in the lactating mammary gland and could also be responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids. The cell surface form functions as a recognition molecule during a variety of cell to cell and cell to matrix interactions, as those occurring during development and egg fertilization, by binding to specific oligosaccharide ligands on opposing cells or in the extracellular matrix.
Catalytic activity	UDP-galactose + D-glucose = UDP + lactose. UDP-galactose + N-acetyl-beta-D-glucosaminylglycopeptide = UDP + beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminylglycopeptide. UDP-galactose + N-acetyl-D-glucosamine = UDP + N-acetyllactosamine.
Cofactor	Manganese By similarity.
Pathway	Protein modification; protein glycosylation.
Subunit structure	Homodimer; and heterodimer with alpha-lactabulmin to form lactose synthase. Ref.12
Subcellular location	Isoform Long: Golgi apparatus › Golgi stack membrane; Single-pass type II membrane protein. Cell membrane; Single-pass type II membrane protein. Cell surface. Note: Found in trans cisternae of Golgi. Ref.11 Isoform Short: Golgi apparatus › Golgi stack membrane; Single-pass type II membrane protein. Note: Found in trans cisternae of Golgi. Ref.11 Processed beta-1,4-galactosyltransferase 1: Secreted. Note: Soluble form found in body fluids. Ref.11
Tissue specificity	Ubiquitously expressed, but at very low levels in fetal and adult brain.
Post-translational modification	The soluble form derives from the membrane forms by proteolytic processing.
Involvement in disease	Defects in B4GALT1 are the cause of congenital disorder of glycosylation type 2D (CDG2D) [MIM:607091]. CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Sequence similarities	Belongs to the glycosyltransferase 7 family.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane Secreted
Coding sequence diversity	Alternative initiation Polymorphism
Disease	Congenital disorder of glycosylation
Domain	Signal-anchor Transmembrane
Ligand	Manganese Metal-binding
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	oligosaccharide biosynthetic process Ref.6 Ref.10 Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell Golgi trans cisterna Inferred from direct assay. Source: UniProtKB basolateral plasma membrane Inferred from direct assay. Source: UniProtKB brush border membrane Inferred from direct assay. Source: UniProtKB desmosome Inferred from direct assay. Source: UniProtKB external side of plasma membrane Inferred from direct assay. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-KW glycocalyx Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	N-acetyllactosamine synthase activity Ref.10 Inferred from direct assay. Source: UniProtKB beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity Inferred from direct assay. Source: UniProtKB lactose synthase activity Inferred from direct assay. Source: UniProtKB manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform Long (identifier: P15291-1)

Also known as: Cell surface;

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.

Note: Found in trans cisternae of Golgi. Ref.11

Isoform Short (identifier: P15291-2)

Also known as: Golgi complex;

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: Missing.

Note: Found in trans cisternae of Golgi. Ref.11

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 398

398

Beta-1,4-galactosyltransferase 1

PRO_0000012278

Chain

? – 398

Processed beta-1,4-galactosyltransferase 1

PRO_0000296229

Regions

Topological domain

1 – 24

24

Cytoplasmic Potential

Transmembrane

25 – 44

20

Signal-anchor for type II membrane protein Potential

Topological domain

45 – 398

354

Lumenal Potential

Sites

Metal binding

250

1

Manganese By similarity

Metal binding

343

1

Manganese By similarity

Site

77 – 78

2

Cleavage; to produce soluble form

Amino acid modifications

Glycosylation

113

1

N-linked (GlcNAc...) Potential

Disulfide bond

130 ↔ 172

By similarity

Disulfide bond

243 ↔ 262

By similarity

Natural variations

Alternative sequence

1 – 13

13

Missing in isoform Short.

VSP_018802

Natural variant

21

1

R → W: dbSNP rs1065764.

VAR_054019

Natural variant

257

1

H → R: dbSNP rs9169.

VAR_054020

Experimental info

Mutagenesis

282

1

Y → G: Reduction In N-acetylglucosamine binding. Ref.10

Mutagenesis

285

1

Y → F: No change in enzymatic activity. Ref.10

Mutagenesis

307

1

Y → G: Reduction In N-acetylglucosamine and UDP-galactose binding. Ref.10

Mutagenesis

308

1

W → G: Reduction In N-acetylglucosamine binding. Ref.10

Mutagenesis

310

1

W → G: Reduction In N-acetylglucosamine binding. Ref.10

Sequence conflict

10

1

G → R Ref.4

Sequence conflict

10

1

G → R Ref.5

Sequence conflict

11

1

Missing Ref.1

Sequence conflict

11

1

Missing Ref.3

Sequence conflict

11

1

Missing Ref.6

Sequence conflict

31 – 32

2

AL → VW in AAA35936. Ref.1

Sequence conflict

31 – 32

2

AL → VW in AAA35937. Ref.1

Sequence conflict

31 – 32

2

AL → VW in AAA68220. Ref.6

Sequence conflict

35

1

G → R in CAA31611. Ref.4

Sequence conflict

76

1

E → D in BAA06188. Ref.5

Sequence conflict

91 – 115

25

SSQPR…ASNLT → GKHAKSSFKQFLLQIKELSN PIDLD in AAA68219. Ref.6

Sequence conflict

212

1

Y → YGIY in CAA32247. Ref.1

Sequence conflict

212

1

Y → YGIY Ref.3

Sequence conflict

260

1

Y → D in AAA68218. Ref.6

Sequence conflict

292

1

L → S in BAA06188. Ref.5

Sequence conflict

337

1

R → T in BAA06188. Ref.5

Sequence conflict

340 – 341

2

MI → PA in AAA68220. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

398

Helix Strand Turn

Details...

Helix

151 – 157

7

Turn

163 – 165

3

Beta strand

170 – 173

4

Beta strand

177 – 186

10

Helix

188 – 204

17

Beta strand

208 – 216

9

Beta strand

218 – 220

3

Helix

224 – 238

15

Beta strand

243 – 247

5

Beta strand

251 – 255

5

Helix

274 – 276

3

Beta strand

288 – 293

6

Helix

294 – 299

6

Beta strand

309 – 312

4

Helix

313 – 322

10

Turn

323 – 325

3

Turn

333 – 336

4

Beta strand

337 – 340

4

Helix

355 – 359

5

Helix

362 – 365

4

Turn

366 – 368

3

Helix

371 – 373

3

Beta strand

377 – 384

8

Beta strand

387 – 393

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long (Cell surface) [UniParc]. Last modified October 17, 2006. Version 5. Checksum: 29B224C83C61E165	FASTA	398	43,920
	10 20 30 40 50 60 MRLREPLLSG SAAMPGASLQ RACRLLVAVC ALHLGVTLVY YLAGRDLSRL PQLVGVSTPL 70 80 90 100 110 120 QGGSNSAAAI GQSSGELRTG GARPPPPLGA SSQPRPGGDS SPVVDSGPGP ASNLTSVPVP 130 140 150 160 170 180 HTTALSLPAC PEESPLLVGP MLIEFNMPVD LELVAKQNPN VKMGGRYAPR DCVSPHKVAI 190 200 210 220 230 240 IIPFRNRQEH LKYWLYYLHP VLQRQQLDYG IYVINQAGDT IFNRAKLLNV GFQEALKDYD 250 260 270 280 290 300 YTCFVFSDVD LIPMNDHNAY RCFSQPRHIS VAMDKFGFSL PYVQYFGGVS ALSKQQFLTI 310 320 330 340 350 360 NGFPNNYWGW GGEDDDIFNR LVFRGMSISR PNAVVGRCRM IRHSRDKKNE PNPQRFDRIA 370 380 390 HTKETMLSDG LNSLTYQVLD VQRYPLYTQI TVDIGTPS
	Isoform Short (Golgi complex). Checksum: A28CB67033107C83	FASTA	385	42,538
	10 20 30 40 50 60 MPGASLQRAC RLLVAVCALH LGVTLVYYLA GRDLSRLPQL VGVSTPLQGG SNSAAAIGQS 70 80 90 100 110 120 SGELRTGGAR PPPPLGASSQ PRPGGDSSPV VDSGPGPASN LTSVPVPHTT ALSLPACPEE 130 140 150 160 170 180 SPLLVGPMLI EFNMPVDLEL VAKQNPNVKM GGRYAPRDCV SPHKVAIIIP FRNRQEHLKY 190 200 210 220 230 240 WLYYLHPVLQ RQQLDYGIYV INQAGDTIFN RAKLLNVGFQ EALKDYDYTC FVFSDVDLIP 250 260 270 280 290 300 MNDHNAYRCF SQPRHISVAM DKFGFSLPYV QYFGGVSALS KQQFLTINGF PNNYWGWGGE 310 320 330 340 350 360 DDDIFNRLVF RGMSISRPNA VVGRCRMIRH SRDKKNEPNP QRFDRIAHTK ETMLSDGLNS 370 380 LTYQVLDVQR YPLYTQITVD IGTPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the full-length coding sequence for human galactosyltransferase (beta-N-acetylglucosaminide: beta 1,4-galactosyltransferase)." Masri K.A., Appert H.E., Fukuda M.N. Biochem. Biophys. Res. Commun. 157:657-663(1988) [PubMed: 3144273] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Near identity of HeLa cell galactosyltransferase with the human placental enzyme." Watzele G., Berger E.G. Nucleic Acids Res. 18:7174-7174(1990) [PubMed: 2124683] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Genomic structure and expression of human beta-1,4-galactosyltransferase." Mengle-Gaw L., McCoy-Haman M.F., Tiemeier D.C. Biochem. Biophys. Res. Commun. 176:1269-1276(1991) [PubMed: 1903938] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complementary DNA cloning for galactosyltransferase associated with tumor and determination of antigenic epitopes recognized by specific monoclonal antibodies." Uejima T., Uemura M., Nozawa S., Narimatsu H. Cancer Res. 52:6158-6163(1992) [PubMed: 1384956] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[5]	"The beta 1, 4-galactosyltransferase gene is post-transcriptionally regulated during differentiation of mouse F9 teratocarcinoma cells." Kudo T., Narimatsu H. Glycobiology 5:397-403(1995) [PubMed: 7579794] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[6]	"Analysis of the sequences of human beta-1,4-galactosyltransferase cDNA clones." Chatterjee S.K., Mukerjee S., Tripathi P.K. Int. J. Biochem. Cell Biol. 27:329-336(1995) [PubMed: 7540104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal liver.
[7]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"Isolation of a cDNA coding for human galactosyltransferase." Appert H.E., Rutherford T.J., Tarr G.E., Wiest J.S., Thomford N.R., McCorquodale D.J. Biochem. Biophys. Res. Commun. 139:163-168(1986) [PubMed: 3094506] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 138-398, PARTIAL PROTEIN SEQUENCE.
[9]	"Isolation of galactosyltransferase from human milk and the determination of its N-terminal amino acid sequence." Appert H.E., Rutherford T.J., Tarr G.E., Thomford N.R., McCorquodale D.J. Biochem. Biophys. Res. Commun. 138:224-229(1986) [PubMed: 3091013] [Abstract] Cited for: PROTEIN SEQUENCE OF 78-94.
[10]	"Analysis of the substrate binding sites of human galactosyltransferase by protein engineering." Aoki D., Appert H.E., Johnson D., Wong S.S., Fukuda M.N. EMBO J. 9:3171-3178(1990) [PubMed: 2120039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 274-326, MUTAGENESIS OF TYR-282; TYR-285; TYR-307; TRP-308 AND TRP-310.
[11]	"Evidence for a molecular distinction between Golgi and cell surface forms of beta 1,4-galactosyltransferase." Lopez L.C., Youakim A., Evans S.C., Shur B.D. J. Biol. Chem. 266:15984-15991(1991) [PubMed: 1714903] [Abstract] Cited for: ALTERNATIVE INITIATION, SUBCELLULAR LOCATION.
[12]	"Golgi retention mechanism of beta-1,4-galactosyltransferase. Membrane-spanning domain-dependent homodimerization and association with alpha- and beta-tubulins." Yamaguchi N., Fukuda M.N. J. Biol. Chem. 270:12170-12176(1995) [PubMed: 7744867] [Abstract] Cited for: SUBUNIT.
[13]	"Identification and characterization of large galactosyltransferase gene families: galactosyltransferases for all functions." Amado M., Almeida R., Schwientek T., Clausen H. Biochim. Biophys. Acta 1473:35-53(1999) [PubMed: 10580128] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Web resources

GeneReviews

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Beta-1,4-galactosyltransferase 1

Cross-references

Sequence databases

EMBLGenBankDDBJ

X14085 mRNA. Translation: CAA32247.1.
M22921 mRNA. Translation: AAA35936.1.
M22921 mRNA. Translation: AAA35937.1.
X55415 mRNA. Translation: CAA39073.1.
X55415 mRNA. Translation: CAA39074.1.
M70432 , M70427, M70428, M70429, M70430, M70431 Genomic DNA. Translation: AAB00776.1.
X13223 mRNA. Translation: CAA31611.1.
D29805 mRNA. Translation: BAA06188.1.
U10472 mRNA. Translation: AAA68218.1.
U10473 mRNA. Translation: AAA68219.1.
U10474 mRNA. Translation: AAA68220.1.
AL161445 Genomic DNA. Translation: CAD13306.1.
M13701 mRNA. Translation: AAA35935.1.

IPI

IPI00215767.
IPI00759755.

PIR

JQ1030.

RefSeq

NP_001488.2.

UniGene

Hs.272011

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AE7	X-ray	2.00	A/B/C	126-397	[»]
2AEC	X-ray	2.00	A/B/C	126-397	[»]
2AES	X-ray	2.00	A/B/C	126-397	[»]
2AGD	X-ray	1.90	A/B/C	126-397	[»]
2AH9	X-ray	2.00	A/B/C	126-397	[»]
2FY7	X-ray	1.70	A	126-397	[»]
2FYA	X-ray	1.90	A	126-397	[»]
2FYB	X-ray	1.90	A	126-397	[»]
3EE5	X-ray	2.20	A/B/C	126-398	[»]

ModBase

Search...

Protein family/group databases

CAZy

GT7. Glycosyltransferase Family 7.

Proteomic databases

PRIDE

P15291.

Genome annotation databases

Ensembl

ENSG00000086062. Homo sapiens. [Contig view]

GeneID

2683.

KEGG

hsa:2683.

UCSC

uc003zsg.2. human.

Organism-specific databases

GeneCards

GC09M033100.

H-InvDB

HIX0025743.

HGNC

HGNC:924. B4GALT1.

HPA

HPA010806.
HPA010807.

MIM

137060. gene.
607091. phenotype.

Orphanet

79332. CDG syndrome, type IId.

PharmGKB

PA25223.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P15291.

OMA

P15291. NAVVGRC.

Enzyme and pathway databases

BRENDA

2.4.1.22. 247.
2.4.1.38. 247.
2.4.1.90. 247.

Gene expression databases

ArrayExpress

P15291.

Bgee

P15291.

CleanEx

HS_B4GALT1.

GermOnline

ENSG00000086062. Homo sapiens.

Family and domain databases

InterPro

IPR003859. Galactosyl_T_2.
[Graphical view]

PANTHER

PTHR19300. Galactosyl_T_2. 1 hit.

Pfam

PF02709. Galactosyl_T_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00141. N-Acetyl-D-glucosamine.

NextBio

10594.

SOURCE

Search...

Entry information

Entry name

B4GT1_HUMAN

Accession

Primary (citable) accession number: P15291
Secondary accession number(s): Q12909 , Q12910, Q12911, Q14456, Q14509, Q14523

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	October 17, 2006
Last modified:	July 7, 2009
This is version 112 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)