A novel I-branching beta-1,6-N-acetylglucosaminyltransferase involved in human blood group I antigen expression.
The human blood group i and I antigens are determined by linear and branched poly-N-acetyllactosamine structures, respectively. In erythrocytes, the fetal i antigen is converted to the adult I antigen by I-branching beta-1,6-N-acetylglucosaminyltransferase (IGnT) during development. Dysfunction of the I-branching enzyme may result in the adult i phenotype in erythrocytes. However, the I gene responsible for blood group I antigen has not been fully confirmed. We report here a novel human I-branching enzyme, designated IGnT3. The genes for IGnT1 (reported in 1993), IGnT2 (also presented in this study), and IGnT3 consist of 3 exons and share the second and third exons. Bone marrow cells preferentially expressed IGnT3 transcript. During erythroid differentiation using CD34(+) cells, IGnT3 was markedly up-regulated with concomitant decrease in IGnT1/2. Moreover, reticulocytes expressed the IGnT3 transcript, but IGnT1/2 was below detectable levels. By molecular genetic analyses of an adult i pedigree, individuals with the adult i phenotype were revealed to have heterozygous alleles with mutations in exon 2 (1006G>A; Gly336Arg) and exon 3 (1049G>A; Gly350Glu), respectively, of the IGnT3 gene. Chinese hamster ovary (CHO) cells transfected with each mutated IGnT3 cDNA failed to express I antigen. These findings indicate that the expression of the blood group I antigen in erythrocytes is determined by a novel IGnT3, not by IGnT1 or IGnT2.
Inaba
Niro
N
National Institute of Advanced Industrial Science and Technology, Glycogene Function Team, Research Center for Glycoscience, Tsukuba, Ibaraki, Japan.
Hiruma
Toru
T
Togayachi
Akira
A
Iwasaki
Hiroko
H
Wang
Xiao-Hui
XH
Furukawa
Yusuke
Y
Sumi
Ryoichi
R
Kudo
Takashi
T
Fujimura
Katsuya
K
Iwai
Toshie
T
Gotoh
Masanori
M
Nakamura
Mitsuru
M
Narimatsu
Hisashi
H
D000328:Adult; D000595:Amino Acid Sequence; D002240:Carbohydrate Sequence; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D006801:Humans; D007048:I Blood-Group System / Q000096:biosynthesis* / Q000737:chemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012156:Reticulocytes / Q000201:enzymology; D014018:Tissue Distribution
D007048:I Blood-Group System; D007527:Isoenzymes; D012333:RNA, Messenger; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases