The leukocyte common antigen (also known as CD45 and PTPRC) is an abundant transmembrane glycoprotein tyrosine phosphatase, which in mammals is present exclusively on the surface of all nucleated hematopoietic cells. CD45 plays a crucial role in maturation, signalling, and function of B and T lymphocytes.
The importance of this molecule for normal immune function is demonstrated by the severe immunodeficiency observed in both mice and humans defective in its surface expression.
The extracellular region of CD45 is heterogeneous and, in mammals, its size depends on the alternative splicing of exons 4, 5, and 6 (also called A, B, and C) which produces at least five different isoforms ranging in size from Mr 180,000 to 220,000. The alternatively spliced region is highly glycosylated with O-linked sugars and is followed by a cysteine-rich region, a region rich in potential N-glycosylation sites and an evolutionarily conserved region containing three fibronectin type III domains. The transmembrane region has 22 residues and is followed by two amino acid domains homologous to tyrosine phosphatases; the first domain seems to have tyrosine phosphatases activity although the presence of both is required for optimal activity. The intracellular domains are known to be involved in the regulation of Src protein tyrosine kinases. CD45 dephosphorylates proteins of this family, which then become activated and start a cascade that leads to proliferation and differentiation of B and T cells.
The function of the extracellular region is still unknown, although in humans, the expression of different isoforms can be used to distinguish CD4+ naive and memory T cells.
The human CD45 gene has 33 exons covering more than 120 kb and contains a large intron of about 50 kb between exons 2 and 3. The structure of the gene in mice is similar, with an extra alternatively spliced exon at the 5' end of the gene. In mice and humans, no TATA box has been found and there are multiple transcription initiation sites.