Cloning of the cDNA for a hematopoietic cell-specific protein related to CD20 and the beta subunit of the high-affinity IgE receptor: evidence for a family of proteins with four membrane-spanning regions.
We report the cloning of the cDNA for a human gene whose mRNA is expressed specifically in hematopoietic cells. A long open reading frame in the 1.7-kb mRNA encodes a 214-aa protein of 25 kDa with four hydrophobic regions consistent with a protein that traverses the membrane four times. To reflect the structure and expression of this gene in diverse hematopoietic lineages of lymphoid and myeloid origin, we named the gene HTm4. The protein is about 20% homologous to two other "four-transmembrane" proteins; the B-cell-specific antigen CD20 and the beta subunit of the high-affinity receptor for IgE, Fc epsilon RI beta. The highest homologies among the three proteins are found in the transmembrane domains, but conserved residues are also recognized in the inter-transmembrane domains and in the N and C termini. Using fluorescence in situ hybridization, we localized HTm4 to human chromosome 11q12-13.1, where the CD20 and Fc epsilon RI beta genes are also located. Both the murine homologue for CD20, Ly-44, and the murine Fc epsilon RI beta gene map to the same region in murine chromosome 19. We propose that the HTm4, CD20, and Fc epsilon RI beta genes evolved from the same ancestral gene to form a family of four-transmembrane proteins. It is possible that other related members exist. Similar to CD20 and Fc epsilon RI beta, it is likely that HTm4 has a role in signal transduction and, like Fc epsilon RI beta, might be a subunit associated with receptor complexes.
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Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215.
Lelias
J M
JM
Kobayashi
H
H
Kaghad
M
M
Morrison
P
P
Rowley
J D
JD
Lim
B
B
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000096:biosynthesis*; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000276:immunology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis*; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C089821:MS4A3 protein, human; D046911:Macromolecular Substances; D008565:Membrane Proteins; D012333:RNA, Messenger; D017455:Receptors, IgE