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GPR65 also known as TDAG8 is a transmembrane protein belonging to the G protein coupled receptor super family with 337-amino acid and 90% similarity and 81% identity in the 7 transmembrane domains of its mouse homolog. It has 3 potential N-linked glycosylation sites and is expressed predominantly in lymphoid organs and cancer tissues with increased expression during activation-induced death of T-cell hybridomas. Two major transcripts of 4.5 kb and 1.8 kb are found in peripheral blood leukocytes and functions as a novel proton-sensing receptor. It couples to adenylyl cyclase and psychosine and is also actively involved in the establishment of immunological autotolerance. GPR65 has a role in cellular transformation by RhoA activation and actin rearrangement under conditions accompanying tissue acidosis.
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