Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype.
The molecular genetic basis of the P histo-blood group system has eluded characterization despite extensive studies of the biosynthesis of the P(1), P, and P(k) glycolipids. The main controversy has been whether a single or two distinct UDP-Gal:Galbeta1-R 4-alpha-galactosyltransferases catalyze the syntheses of the structurally related P(1) and P(k) antigens. The P(1) polymorphism is linked to 22q11.3-ter. Data base searches with the coding region of an alpha4GlcNAc-transferase identified a novel homologous gene at 22q13.2 designated alpha4Gal-T1. Expression of full coding constructs of alpha4Gal-T1 in insect cells revealed it encoded P(k) but not P(1) synthase activity. Northern analysis showed expression of the transcript correlating with P(k) synthase activity and antigen expression in human B cell lines. Transfection of P(k)-negative Namalwa cells with alpha4Gal-T1 resulted in strong P(k) expression. A single homozygous missense mutation, M183K, was found in six Swedish individuals of the rare p phenotype, confirming that alpha4Gal-T1 represented the P(k) gene. Sequence analysis of the coding region of alpha4Gal-T1 in P(1)+/- individuals did not reveal polymorphisms correlating with P(1)P(2) typing.
Steffensen
R
R
School of Dentistry, University of Copenhagen, Norre Allé 20, 2200 Copenhagen N, Denmark.
Carlier
K
K
Wiels
J
J
Levery
S B
SB
Stroud
M
M
Cedergren
B
B
Nilsson Sojka
B
B
Bennett
E P
EP
Jersild
C
C
Clausen
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D002240:Carbohydrate Sequence; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D005700:Galactosyltransferases / Q000737:chemistry / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010127:P Blood-Group System / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
D010127:P Blood-Group System; D005700:Galactosyltransferases; C410407:UDP-galactose - Galbeta1-4Glcbeta1-Cer alpha1,4-galactosyltransferase