Three Genes in the Human MHC Class III Region near the Junction with the Class II: Gene for Receptor of Advanced Glycosylation End Products, PBX2 Homeobox Gene and a Notch Homolog, Human Counterpart of Mouse Mammary Tumor Gene int-3

Cosmid walking of about 250 kb from MHC class III gene CYP21 to class lI was conducted. The gene for receptor of advanced glycosylation end products of proteins (RAGE, a member of immunoglobulin super-family molecules), the PBX2 homeohox gene designated HOXI2, and the human counterpart of the mouse mammary tumor gene int-3 were found. The contiguous RAGE and HOX12 genes were completely sequenced, and the human int-3 counterpart was partially sequenced and assigned to a Notch homolog. This human Notch homolog, designated NOTCH3, showed both the intracellular portion present in the mouse int-3 sequence and the extracellular portion absent in the int-3. It thus corresponds to the intact form of a Notch-type transmembrane protein. About 20 kb of dense Alu clustering was found just centromeric to the NOTCH3.