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The Journal of Immunology, Vol 159, Issue 8 3858-3865, Copyright © 1997 by American Association of Immunologists

ARTICLES

Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase

E Ferrero and F Malavasi
Department of Genetics, Biology, and Medical Chemistry, University of Torino, Italy.

The human leukocyte Ag CD38 is a 45-kDa type II membrane glycoprotein that functions both as a transmembrane signaling receptor and as an ectoenzyme. CD38 can transmit positive or negative signals regulating T and B lymphocyte proliferation and differentiation and can enzymatically convert nicotinamide adenine dinucleotide to cyclic ADP- ribose, a potent intracellular calcium releaser. To begin the genetic analysis of CD38, we have isolated and characterized the human CD38 gene, previously mapped to chromosome 4. Human CD38 is encoded by a single copy gene that extends over > 62 kb and consists of eight exons and seven introns, including a very long intron that interrupts the 5' coding region. The 5' upstream region of the gene is characterized by the absence of canonical TATA and CAAT boxes, the presence of a GC-rich tract immediately upstream of the initiator codon, several transcription start sites, and potential binding sites for the immunologic transcription factors T cell-specific transcription factor alpha, nuclear factor-IL-6, and interferon responsive factor-1. Comparison of the genomic structure of human CD38 with that of the genes for murine bone marrow stromal Ag bone marrow stromal cell antigen 1/BP-3 and aplysian ADP-ribosyl cyclase, which encode proteins related to CD38 in sequence and function, reveals their striking structural similarity. This strongly suggests that the three genes evolved from a common ancestor from which CD38 and bone marrow stromal cell antigen 1 arose by gene duplication before the divergence of humans and rodents.


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