This gene encodes a member of the adhesion-GPCR receptor family  expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal protein modules coupled to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain. In the case of CD97 the N-terminal domains consist of alternatively spliced epidermal growth factor (EGF)-like domains. These mediate binding to its cellular ligand, decay accelerating factor (DAF/CD55), a regulatory protein of the complement cascade, however the CD55-CD97 interaction is believed to have an activity independent of complement. Alternative splicing has been observed for this gene and three variants have been found.
CD97 is an adhesion GPCR that is normally found on tissue of hematapoetic origin and in smooth muscle. It signals through Gα12/13 and activates RHO. It has been found to be upregulated in Cancers, including prostate, breast, and thyroid. In prostate cancer. it has been shown that CD97 is hetoerodimerizing with another GPCR, LPAR. The interaction is believed to further enhance the RHO signaling between both receptors.
^Hamann J, Eichler W, Hamann D, Kerstens HM, Poddighe PJ, Hoovers JM, Hartmann E, Strauss M, van Lier RA (Sep 1995). "Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of the secretion receptor superfamily with an unusual extracellular domain". J Immunol155 (4): 1942–50. PMID7636245.
^Hamann J, Hartmann E, van Lier RA (Sep 1996). "Structure of the human CD97 gene: exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily". Genomics32 (1): 144–7. doi:10.1006/geno.1996.0092. PMID8786105.
^Ward, Y., R. Lake, J. J. Yin, C. D. Heger, M. Raffeld, P. K. Goldsmith, M. Merino, K. Kelly. 2011. LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells" Cancer Res 71: 7301–7311.
^Ward Y, Lake R, Martin P L, Killian K, Salerno P, Wang T, Meltzer P, Merino M, Cheng S-Y, Santoro M, Garcia-Rostan G, Kelly K,CD97 amplifies LPA receptor signaling and promotes thyroid cancer progression in a mouse model. Oncogene. 2012/07/16/online
Mustafa T, Klonisch T, Hombach-Klonisch S, Kehlen A, Schmutzler C, Koehrle J, Gimm O, Dralle H, Hoang-Vu C (February 2004). "Expression of CD97 and CD55 in human medullary thyroid carcinomas". Int. J. Oncol.24 (2): 285–94. doi:10.3892/ijo.24.2.285. PMID14719104.
Mustafa T, Eckert A, Klonisch T, Kehlen A, Maurer P, Klintschar M, Erhuma M, Zschoyan R, Gimm O, Dralle H, Schubert J, Hoang-Vu C (January 2005). "Expression of the epidermal growth factor seven-transmembrane member CD97 correlates with grading and staging in human oral squamous cell carcinomas". Cancer Epidemiol. Biomarkers Prev.14 (1): 108–19. PMID15668483.
Aust G, Eichler W, Laue S et al. (1997). "CD97: a dedifferentiation marker in human thyroid carcinomas". Cancer Res.57 (9): 1798–806. PMID9135025.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Ghannadan M, Baghestanian M, Wimazal F et al. (1998). "Phenotypic characterization of human skin mast cells by combined staining with toluidine blue and CD antibodies". J. Invest. Dermatol.111 (4): 689–95. doi:10.1046/j.1523-1747.1998.00359.x. PMID9764855.
Eichler W (2000). "CD97 isoform expression in leukocytes". J. Leukoc. Biol.68 (4): 561–7. PMID11037979.
Lin HH, Stacey M, Saxby C et al. (2001). "Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex". J. Biol. Chem.276 (26): 24160–9. doi:10.1074/jbc.M101770200. PMID11297558.
Stacey M, Chang GW, Davies JQ et al. (2003). "The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans". Blood102 (8): 2916–24. doi:10.1182/blood-2002-11-3540. PMID12829604.
Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet.36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.