MOLECULAR CHARACTERIZATION AND CHROMOSOME LOCALIZATION OF A HUMAN ANGIOTENSIN-II AT2 RECEPTOR GENE HIGHLY EXPRESSED IN FETAL TISSUES

The gene encoding the human angiotensin IT (AT2) receptor exists as a single copy and contains no intron in its coding region. Its nucleotid e sequence is identical to that of cDNA clones isolated from human myo metrial library. In addition, binding properties of the corresponding receptor expressed in COS cells are identical to those of endogenous A T2 receptors from human myometrium. The human AT2 receptor gene transl ates into a polypeptide of 363 amino-acid residues that belongs to the seven transmembrane domains receptor superfamily. This polypeptide sh ows 92% amino-acid sequence homology and the same pharmacological prof ile as AT2 receptors recently isolated from rat and mouse. The AT2 rec eptor gene maps to the X chromosome in man (region Xq24-q25) as well a s in mouse (region XA2 - A4). These findings open new perspectives reg arding a potential involvement of AT2 receptors in X-linked congenital diseases. Expression of AT2 receptor mRNA is found in human myometriu m, fallopian tubes and adrenals, and at extremely high levels in fetal kidney and intestine. These results indicate that AT2 receptor gene e xpression is regulated during human embryonic development, and support the hypothesis that AT2 receptors may play a role in organogenesis.