UniProtKB - Q9NPC4 (A4GAT_HUMAN)
Protein
Lactosylceramide 4-alpha-galactosyltransferase
Gene
A4GALT
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the transfer of galactose from UDP-alpha-D-galactose to lactosylceramide/beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide(d18:1(4E)) to produce globotriaosylceramide/globoside Gb3Cer (d18:1(4E)) (PubMed:10748143). Also able to transfer galactose to galactosylceramide/beta-D-Gal-(1<->1')-Cer (PubMed:10748143). Globoside Gb3Cer is a glycosphingolipid of the globo serie, one of the major types of neutral root structures of glycosphingolipids, that constitute a significant portion of mammalian cell membranes (Probable). Globotriaosylceramide/globoside Gb3Cer in blood and tissue cell membranes is the antigen Pk of blood histogroup P (PubMed:10747952).1 Publication2 Publications
(Microbial infection) Globotriaosylceramide is one of the cellular ligands for bacterial verotoxins.1 Publication
Catalytic activityi
- a β-D-Gal-(1→4)-β-D-Glc-(1↔1)-Cer(d18:1(4E)) + UDP-α-D-galactose = globoside Gb3Cer (d18:1(4E)) + H+ + UDP1 PublicationEC:2.4.1.2281 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=54.5 µM for beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide(d18:1(4E))1 Publication
- KM=132 µM for beta-D-Gal-(1<->1')-Cer1 Publication
: Glycolipid biosynthesis Pathwayi
This protein is involved in Glycolipid biosynthesis.1 PublicationView all proteins of this organism that are known to be involved in Glycolipid biosynthesis.
GO - Molecular functioni
- galactosyltransferase activity Source: UniProtKB
- lactosylceramide 4-alpha-galactosyltransferase activity Source: UniProtKB-EC
- toxic substance binding Source: Ensembl
- transferase activity, transferring hexosyl groups Source: GO_Central
GO - Biological processi
- globoside biosynthetic process Source: Ensembl
- glycosphingolipid biosynthetic process Source: GO_Central
- plasma membrane organization Source: MGI
Keywordsi
Molecular function | Glycosyltransferase, Transferase |
Biological process | Lipid biosynthesis, Lipid metabolism |
Enzyme and pathway databases
BioCyci | MetaCyc:HS05171-MONOMER |
BRENDAi | 2.4.1.228, 2681 |
PathwayCommonsi | Q9NPC4 |
Protein family/group databases
CAZyi | GT32, Glycosyltransferase Family 32 |
Chemistry databases
SwissLipidsi | SLP:000000760 |
Names & Taxonomyi
Protein namesi | Recommended name: Lactosylceramide 4-alpha-galactosyltransferase (EC:2.4.1.2281 Publication)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 namesi | Name:A4GALT Synonyms:A14GALT, A4GALT1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18149, A4GALT |
MIMi | 607922, gene |
neXtProti | NX_Q9NPC4 |
VEuPathDBi | HostDB:ENSG00000128274.15 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus membrane Curated; Single-pass type II membrane protein Curated
Golgi apparatus
- integral component of Golgi membrane Source: UniProtKB
Other locations
- membrane Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 22 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 23 – 43 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 44 – 353 | LumenalSequence analysisAdd BLAST | 310 |
Keywords - Cellular componenti
Golgi apparatus, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 53947 |
MalaCardsi | A4GALT |
MIMi | 111400, phenotype |
OpenTargetsi | ENSG00000128274 |
PharmGKBi | PA24359 |
Miscellaneous databases
Pharosi | Q9NPC4, Tbio |
Genetic variation databases
BioMutai | A4GALT |
DMDMi | 25452796 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080578 | 1 – 353 | Lactosylceramide 4-alpha-galactosyltransferaseAdd BLAST | 353 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 121 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 203 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | Q9NPC4 |
jPOSTi | Q9NPC4 |
MassIVEi | Q9NPC4 |
PaxDbi | Q9NPC4 |
PeptideAtlasi | Q9NPC4 |
PRIDEi | Q9NPC4 |
ProteomicsDBi | 81966 |
PTM databases
GlyGeni | Q9NPC4, 4 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q9NPC4 |
PhosphoSitePlusi | Q9NPC4 |
Expressioni
Tissue specificityi
Ubiquitous. Highly expressed in kidney, heart, spleen, liver, testis and placenta.
Gene expression databases
Bgeei | ENSG00000128274, Expressed in heart left ventricle and 163 other tissues |
ExpressionAtlasi | Q9NPC4, baseline and differential |
Genevisiblei | Q9NPC4, HS |
Organism-specific databases
HPAi | ENSG00000128274, Low tissue specificity |
Interactioni
Protein-protein interaction databases
BioGRIDi | 119825, 7 interactors |
IntActi | Q9NPC4, 6 interactors |
MINTi | Q9NPC4 |
STRINGi | 9606.ENSP00000384794 |
Miscellaneous databases
RNActi | Q9NPC4, protein |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 192 – 194 | DXD motifBy similarity | 3 |
Domaini
The conserved DXD motif is involved in enzyme activity.By similarity
Sequence similaritiesi
Belongs to the glycosyltransferase 32 family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1928, Eukaryota |
GeneTreei | ENSGT00510000047981 |
HOGENOMi | CLU_049512_2_0_1 |
InParanoidi | Q9NPC4 |
OMAi | ESHACRG |
OrthoDBi | 1082380at2759 |
PhylomeDBi | Q9NPC4 |
TreeFami | TF324053 |
Family and domain databases
InterProi | View protein in InterPro IPR007652, A1-4-GlycosylTfrase_dom IPR007577, GlycoTrfase_DXD_sugar-bd_CS IPR029044, Nucleotide-diphossugar_trans |
Pfami | View protein in Pfam PF04572, Gb3_synth, 1 hit PF04488, Gly_transf_sug, 1 hit |
SUPFAMi | SSF53448, SSF53448, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9NPC4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSKPPDLLLR LLRGAPRQRV CTLFIIGFKF TFFVSIMIYW HVVGEPKEKG
60 70 80 90 100
QLYNLPAEIP CPTLTPPTPP SHGPTPGNIF FLETSDRTNP NFLFMCSVES
110 120 130 140 150
AARTHPESHV LVLMKGLPGG NASLPRHLGI SLLSCFPNVQ MLPLDLRELF
160 170 180 190 200
RDTPLADWYA AVQGRWEPYL LPVLSDASRI ALMWKFGGIY LDTDFIVLKN
210 220 230 240 250
LRNLTNVLGT QSRYVLNGAF LAFERRHEFM ALCMRDFVDH YNGWIWGHQG
260 270 280 290 300
PQLLTRVFKK WCSIRSLAES RACRGVTTLP PEAFYPIPWQ DWKKYFEDIN
310 320 330 340 350
PEELPRLLSA TYAVHVWNKK SQGTRFEATS RALLAQLHAR YCPTTHEAMK
MYL
Polymorphismi
Genetic variation in A4GALT is responsible for the P1PK system blood group phenotypes [MIMi: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 (PubMed:10993874, PubMed:11896312). Genetic variation in A4GALT is also responsible for the NOR polyagglutination syndrome [MIMi:111400]. Polyagglutination is the occurrence of red cell agglutination by virtually all human sera, but not by autologous serum or sera from newborns, creating a risk of complications during transfusions of NOR erythrocytes. It is caused by the unusual Gal(alpha1-4)GalNAc glycolipid epitope (PubMed:22965229).3 Publications
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014296 | 37 | M → V3 PublicationsCorresponds to variant dbSNP:rs11541159Ensembl. | 1 | |
Natural variantiVAR_017507 | 80 | Missing in p individuals. 1 Publication | 1 | |
Natural variantiVAR_022320 | 163 | Q → R1 PublicationCorresponds to variant dbSNP:rs28915383EnsemblClinVar. | 1 | |
Natural variantiVAR_014297 | 183 | M → K in p individuals; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs74315453EnsemblClinVar. | 1 | |
Natural variantiVAR_017508 | 187 | G → D in p individuals; partial loss of activity. 1 PublicationCorresponds to variant dbSNP:rs28940572EnsemblClinVar. | 1 | |
Natural variantiVAR_080910 | 211 | Q → E in individuals with NOR polyagglutination syndrome; causes the synthesis of both Gal(alpha1-4)Gal and Gal(alpha1-4)GalNAc moieties. 1 PublicationCorresponds to variant dbSNP:rs397514502EnsemblClinVar. | 1 | |
Natural variantiVAR_017509 | 251 | P → L in p individuals; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs28940571EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 No translation available. CH471138 Genomic DNA Translation: EAW73274.1 BC017068 mRNA Translation: AAH17068.1 |
CCDSi | CCDS14041.1 |
RefSeqi | NP_001304967.1, NM_001318038.1 NP_059132.1, NM_017436.5 XP_005261701.1, XM_005261644.2 XP_005261703.1, XM_005261646.4 XP_005261704.1, XM_005261647.2 XP_005261705.1, XM_005261648.3 XP_006724328.1, XM_006724265.3 XP_006724329.1, XM_006724266.3 XP_011528535.1, XM_011530233.2 XP_016884320.1, XM_017028831.1 |
Genome annotation databases
Ensembli | ENST00000249005; ENSP00000249005; ENSG00000128274 ENST00000381278; ENSP00000370678; ENSG00000128274 ENST00000401850; ENSP00000384794; ENSG00000128274 ENST00000642412; ENSP00000494127; ENSG00000128274 |
GeneIDi | 53947 |
KEGGi | hsa:53947 |
UCSCi | uc062ewk.1, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Functional Glycomics Gateway - GTase Lactosylceramide 4-alpha-galactosyltransferase |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 No translation available. CH471138 Genomic DNA Translation: EAW73274.1 BC017068 mRNA Translation: AAH17068.1 |
CCDSi | CCDS14041.1 |
RefSeqi | NP_001304967.1, NM_001318038.1 NP_059132.1, NM_017436.5 XP_005261701.1, XM_005261644.2 XP_005261703.1, XM_005261646.4 XP_005261704.1, XM_005261647.2 XP_005261705.1, XM_005261648.3 XP_006724328.1, XM_006724265.3 XP_006724329.1, XM_006724266.3 XP_011528535.1, XM_011530233.2 XP_016884320.1, XM_017028831.1 |
3D structure databases
SMRi | Q9NPC4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119825, 7 interactors |
IntActi | Q9NPC4, 6 interactors |
MINTi | Q9NPC4 |
STRINGi | 9606.ENSP00000384794 |
Chemistry databases
SwissLipidsi | SLP:000000760 |
Protein family/group databases
CAZyi | GT32, Glycosyltransferase Family 32 |
PTM databases
GlyGeni | Q9NPC4, 4 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q9NPC4 |
PhosphoSitePlusi | Q9NPC4 |
Genetic variation databases
BioMutai | A4GALT |
DMDMi | 25452796 |
Proteomic databases
EPDi | Q9NPC4 |
jPOSTi | Q9NPC4 |
MassIVEi | Q9NPC4 |
PaxDbi | Q9NPC4 |
PeptideAtlasi | Q9NPC4 |
PRIDEi | Q9NPC4 |
ProteomicsDBi | 81966 |
Protocols and materials databases
Antibodypediai | 239, 223 antibodies |
DNASUi | 53947 |
Genome annotation databases
Ensembli | ENST00000249005; ENSP00000249005; ENSG00000128274 ENST00000381278; ENSP00000370678; ENSG00000128274 ENST00000401850; ENSP00000384794; ENSG00000128274 ENST00000642412; ENSP00000494127; ENSG00000128274 |
GeneIDi | 53947 |
KEGGi | hsa:53947 |
UCSCi | uc062ewk.1, human |
Organism-specific databases
CTDi | 53947 |
DisGeNETi | 53947 |
GeneCardsi | A4GALT |
HGNCi | HGNC:18149, A4GALT |
HPAi | ENSG00000128274, Low tissue specificity |
MalaCardsi | A4GALT |
MIMi | 111400, phenotype 607922, gene |
neXtProti | NX_Q9NPC4 |
OpenTargetsi | ENSG00000128274 |
PharmGKBi | PA24359 |
VEuPathDBi | HostDB:ENSG00000128274.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1928, Eukaryota |
GeneTreei | ENSGT00510000047981 |
HOGENOMi | CLU_049512_2_0_1 |
InParanoidi | Q9NPC4 |
OMAi | ESHACRG |
OrthoDBi | 1082380at2759 |
PhylomeDBi | Q9NPC4 |
TreeFami | TF324053 |
Enzyme and pathway databases
BioCyci | MetaCyc:HS05171-MONOMER |
BRENDAi | 2.4.1.228, 2681 |
PathwayCommonsi | Q9NPC4 |
Miscellaneous databases
BioGRID-ORCSi | 53947, 8 hits in 875 CRISPR screens |
ChiTaRSi | A4GALT, human |
GeneWikii | A4GALT |
GenomeRNAii | 53947 |
Pharosi | Q9NPC4, Tbio |
PROi | PR:Q9NPC4 |
RNActi | Q9NPC4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000128274, Expressed in heart left ventricle and 163 other tissues |
ExpressionAtlasi | Q9NPC4, baseline and differential |
Genevisiblei | Q9NPC4, HS |
Family and domain databases
InterProi | View protein in InterPro IPR007652, A1-4-GlycosylTfrase_dom IPR007577, GlycoTrfase_DXD_sugar-bd_CS IPR029044, Nucleotide-diphossugar_trans |
Pfami | View protein in Pfam PF04572, Gb3_synth, 1 hit PF04488, Gly_transf_sug, 1 hit |
SUPFAMi | SSF53448, SSF53448, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | A4GAT_HUMAN | |
Accessioni | Q9NPC4Primary (citable) accession number: Q9NPC4 Secondary accession number(s): B2R7C4, Q9P1X5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 25, 2002 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 10, 2021 | |
This is version 173 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants