Evi27 encodes a novel membrane protein with homology to the IL17 receptor

Evi27 is a common site of retroviral integration in BXH2 murine myeloid leu kemias. Here me show that integration at Evi27 occurs in a CpG island simil ar to 6 kb upstream from a novel gene (designated Evi27) with homology to t he IL17 receptor (Il17r) and that proviral integrations result in increased expression of the Evi27 protein on the cell surface. The human EVI27 homol ogy was also cloned and mapped to chromosome 3p21, Multiple Evi27 isoforms were detected at the RNA and protein level in both human and mouse, indicat ing that Evi27 expression is complex. Some of the isoforms are shown to lik ely represent secreted soluble forms of the protein produced by intron inco rporation or by proteolytic cleavage. In the mouse, highest Evi27 expressio n occurs in liver and testes with lower expression in kidney and lung, In h umans, EVI27 is expressed at high levels in the kidney, with moderate level s in the liver, brain, and testes. Within hematopoietic cells, Evi27 expres sion is restricted. Northern and Western analysis showed that Evi27 is expr essed in selected T-cell B-cell and myeloid cell lines. These results sugge st that Evi27 expression is tightly regulated during hematopoietic differen tiation. Collectively, these studies identify a nea member of the cytokine receptor family whose increased and uncoordinated expression may lead to my eloid leukemia by altering Evi27's normal ability to control the growth and /or differentiation of hematopoietic cells.