Q9NPC4 (A4GAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lactosylceramide 4-alpha-galactosyltransferase
EC=2.4.1.228

Alternative name(s):
Alpha-1,4-N-acetylglucosaminyltransferase
Alpha-1,4-galactosyltransferase
Alpha4Gal-T1
CD77 synthase
Globotriaosylceramide synthase
Short name=Gb3 synthase
P1/Pk synthase
UDP-galactose:beta-D-galactosyl-beta1-R 4-alpha-D-galactosyltransferase

Gene names

Name:	A4GALT
Synonyms:	A14GALT, A4GALT1

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	353 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Necessary for the biosynthesis of the Pk antigen of blood histogroup P. Catalyzes the transfer of galactose to lactosylceramide and galactosylceramide. Necessary for the synthesis of the receptor for bacterial verotoxins.
Catalytic activity	UDP-alpha-D-galactose + beta-D-galactosyl-(1->4)-D-glucosyl-(1<->1)-ceramide = UDP + alpha-D-galactosyl-(1->4)-beta-D-galactosyl-(1->4)-D-glucosyl-(1<->1)-ceramide.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein Probable.
Tissue specificity	Ubiquitous. Highly expressed in kidney, heart, spleen, liver, testis and placenta.
Domain	The conserved DXD motif is involved in enzyme activity By similarity.
Polymorphism	Genetic variation in A4GALT is responsible for the P system blood group phenotypes [MIM:111400]. Different combinations or absence of the P blood group system antigens define 5 different phenotypes: P1, P2, P1(k), P2(k), and p. Genetic variation in A4GALT determines the p phenotype, which is rare and does not express any antigens. It is also known as null phenotype; p individuals have antibodies against P, P1 and Pk antigens in their sera. These antibodies are clinically important because they can cause severe transfusion reactions and miscarriage.
Sequence similarities	Belongs to the glycosyltransferase 32 family.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycosphingolipid biosynthetic process Non-traceable author statement Ref.1. Source: UniProtKB plasma membrane organization Inferred from direct assay Ref.2. Source: MGI protein glycosylation Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	Golgi stack Inferred from electronic annotation. Source: InterPro integral to Golgi membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	galactosyltransferase activity Inferred from direct assay Ref.2. Source: UniProtKB lactosylceramide 4-alpha-galactosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 353	353	Lactosylceramide 4-alpha-galactosyltransferase		PRO_0000080578
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 43	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	44 – 353	310	Lumenal Potential
	Motif	192 – 194	3	DXD motif By similarity
Amino acid modifications
	Glycosylation	121	1	N-linked (GlcNAc...) Potential
	Glycosylation	203	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	37	1	M → V. Ref.2 Ref.4 Ref.9 Corresponds to variant rs11541159 [ dbSNP | Ensembl ].		VAR_014296
	Natural variant	80	1	Missing in p individuals. Ref.10		VAR_017507
	Natural variant	163	1	Q → R. Ref.4 Corresponds to variant rs28915383 [ dbSNP | Ensembl ].		VAR_022320
	Natural variant	183	1	M → K in p individuals; complete loss of activity. Ref.2 Ref.9		VAR_014297
	Natural variant	187	1	G → D in p individuals; partial loss of activity. Ref.9 Corresponds to variant rs28940572 [ dbSNP | Ensembl ].		VAR_017508
	Natural variant	251	1	P → L in p individuals; complete loss of activity. Ref.9 Corresponds to variant rs28940571 [ dbSNP | Ensembl ].		VAR_017509

Sequences

	Sequence		Length	Mass (Da)
	Q9NPC4 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 8755865BDA5DA205	FASTA	353	40,499
	10 20 30 40 50 60 MSKPPDLLLR LLRGAPRQRV CTLFIIGFKF TFFVSIMIYW HVVGEPKEKG QLYNLPAEIP 70 80 90 100 110 120 CPTLTPPTPP SHGPTPGNIF FLETSDRTNP NFLFMCSVES AARTHPESHV LVLMKGLPGG 130 140 150 160 170 180 NASLPRHLGI SLLSCFPNVQ MLPLDLRELF RDTPLADWYA AVQGRWEPYL LPVLSDASRI 190 200 210 220 230 240 ALMWKFGGIY LDTDFIVLKN LRNLTNVLGT QSRYVLNGAF LAFERRHEFM ALCMRDFVDH 250 260 270 280 290 300 YNGWIWGHQG PQLLTRVFKK WCSIRSLAES RACRGVTTLP PEAFYPIPWQ DWKKYFEDIN 310 320 330 340 350 PEELPRLLSA TYAVHVWNKK SQGTRFEATS RALLAQLHAR YCPTTHEAMK MYL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids." Kojima Y., Fukumoto S., Furukawa K., Okajima T., Wiels J., Yokoyama K., Suzuki Y., Urano T., Ohta M., Furukawa K. J. Biol. Chem. 275:15152-15156(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Melanoma.
[2]	"Cloning and expression of the histo-blood group Pk UDP-galactose:Galbeta1-4Glcbeta1-Cer alpha1,4-galactosyltransferase. Molecular genetic basis of the p phenotype." Steffensen R., Carlier K., Wiels J., Levery S.B., Stroud M., Cedergren B., Nilsson Sojka B., Bennett E.P., Jersild C., Clausen H. J. Biol. Chem. 275:16723-16729(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-37 AND LYS-183.
[3]	"Human-specific amino acid changes found in 103 protein-coding genes." Kitano T., Liu Y.-H., Ueda S., Saitou N. Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	SeattleSNPs variation discovery resource Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-37 AND ARG-163.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue.
[6]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: Uterus.
[9]	"Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals." Furukawa K., Iwamura K., Uchikawa M., Sojka B.N., Wiels J., Okajima T., Urano T., Furukawa K. J. Biol. Chem. 275:37752-37756(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VAL-37; LYS-183; ASP-187 AND LEU-251.
[10]	"Three-base deletion and one-base insertion of the alpha(1,4)galactosyltransferase gene responsible for the P phenotype." Koda Y., Soejima M., Sato H., Maeda Y., Kimura H. Transfusion 42:48-51(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PHE-80 DEL.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

SeattleSNPs

Functional Glycomics Gateway - GTase

Lactosylceramide 4-alpha-galactosyltransferase

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB037883 mRNA. Translation: BAA95915.1. AJ245581 mRNA. Translation: CAB93532.1. AB041418 Genomic DNA. Translation: BAA94503.1. AY941797 Genomic DNA. Translation: AAX20109.1. AK312927 mRNA. Translation: BAG35771.1. Z82176 Genomic DNA. Translation: CAI18757.1. CH471138 Genomic DNA. Translation: EAW73274.1. BC017068 mRNA. Translation: AAH17068.1.
IPI	IPI00033541.
RefSeq	NP_059132.1. NM_017436.4.
UniGene	Hs.105956.
3D structure databases
ProteinModelPortal	Q9NPC4.
SMR	Q9NPC4. Positions 171-227.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-5210812.
STRING	9606.ENSP00000249005.
Protein family/group databases
CAZy	GT32. Glycosyltransferase Family 32.
PTM databases
PhosphoSite	Q9NPC4.
Polymorphism databases
DMDM	25452796.
Proteomic databases
PaxDb	Q9NPC4.
PRIDE	Q9NPC4.
Protocols and materials databases
DNASU	53947.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249005; ENSP00000249005; ENSG00000128274. ENST00000381278; ENSP00000370678; ENSG00000128274. ENST00000401850; ENSP00000384794; ENSG00000128274.
GeneID	53947.
KEGG	hsa:53947.
UCSC	uc003bdb.3. human.
Organism-specific databases
CTD	53947.
GeneCards	GC22M043088.
HGNC	HGNC:18149. A4GALT.
HPA	HPA001141.
MIM	111400. phenotype. 607922. gene.
neXtProt	NX_Q9NPC4.
PharmGKB	PA24359.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG251623.
HOVERGEN	HBG050427.
InParanoid	Q9NPC4.
KO	K01988.
OrthoDB	EOG4NVZKK.
PhylomeDB	Q9NPC4.
Enzyme and pathway databases
BRENDA	2.4.1.228. 2681.
UniPathway	UPA00378.
Gene expression databases
ArrayExpress	Q9NPC4.
Bgee	Q9NPC4.
CleanEx	HS_A4GALT.
Genevestigator	Q9NPC4.
GermOnline	ENSG00000128274. Homo sapiens.
Family and domain databases
InterPro	IPR007652. A1-4-GlycosylTfrase_dom. IPR007577. GlycoTrfase_DXD_sugar-bd_CS. [Graphical view]
Pfam	PF04572. Gb3_synth. 1 hit. PF04488. Gly_transf_sug. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	53947.
NextBio	56264.
SOURCE	Search...

Entry information

Entry name

A4GAT_HUMAN

Accession

Primary (citable) accession number: Q9NPC4
Secondary accession number(s): B2R7C4, Q9P1X5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 25, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 112 of the entry and version 1 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.