JAW1, A LYMPHOID-RESTRICTED MEMBRANE-PROTEIN LOCALIZED TO THE ENDOPLASMIC-RETICULUM

Jaw1 is a novel lymphoid-restricted gene that is expressed in a develo pmentally regulated fashion in both the B and T cell lineages. Jaw1 mR NA is abundantly expressed in pre-B and B cell lines with minimal or u ndetectable expression in plasma cell lines. Pre-T cell lines and norm al mouse thymocytes express high levels of Jaw1 mRNA, whereas most mat ure T cell lines express low levels. Comparison of the mouse and human genes reveals that Jaw1 encodes a 539 amino acid protein with a highl y conserved coiled-coil domain in the middle third of the protein and a COOH-terminal transmembrane domain. Jaw1 was localized to the endopl asmic reticulum (ER) of lymphocytes by indirect immunofluorescence and confocal microscopy. When overexpressed in Hela cells, Jaw1 protein t argeted to the ER. In vitro translation of Jaw1 in the presence of can ine microsomes demonstrated that Jaw1 is an integral membrane protein of the ER and is oriented on the ER membrane facing the cytosol. Jaw1 is a member of a class of proteins with COOH-terminal hydrophobic memb rane anchors and is structurally similar to proteins involved in vesic le targeting and fusion. These findings suggest that the function and/ or the structure of the ER in lymphocytes may be modified by lymphoid- restricted resident ER proteins.