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.
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.
Ferrero
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E
Department of Genetics, Biology, and Medical Chemistry, University of Torino, Italy.
Malavasi
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics*; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics*; D001048:Aplysia / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D005091:Exons; D058851:GPI-Linked Proteins; D006801:Humans; D007438:Introns; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D005810:Multigene Family / Q000276:immunology*; D009244:NAD+ Nucleosidase / Q000737:chemistry / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D015703:Antigens, CD; D000943:Antigens, Differentiation; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D011971:Receptors, Immunologic; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1