FXYD domain-containing ion transport regulator 5 also named dysadherin (human) or RIC (mouse) is a protein that in humans is encoded by the FXYD5gene.[5]
Function
This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. This gene product, FXYD5, has not been characterized as a protein. Two transcript variants have been found for this gene, and they are both predicted to encode the same protein.[5]
Dysadherin is the gamma5 subunit the human Na,K-ATPase. Of all the FXYD members, dysadherin is the only member that has a large extracellular sequence of 140 amino acids. Dysadherin has been observed to be over-expressed on the surface of cells that have down regulated levels of surface E-cadherin. CCL2 (bone homing cytokine)is a protein that is highly affected by silencing dysadherin expression. Dysadherin interferes with cell adhesion via beta1 subunit interactions.[6] Dysdaherin is a target for an extracellular antibody drug conjugate where the antibody to dysadherin is attached to a cardiac glycoside.[7]
Clinical significance
Dysadherin has been found to be a marker for metastatic cancers and found up-regulated in multiple cancer types.[7]
Sweadner KJ, Rael E (August 2000). "The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression". Genomics. 68 (1): 41–56. doi:10.1006/geno.2000.6274. PMID10950925.
Omasa T, Chen YG, Mantalaris A, Wu JH (January 2001). "A cDNA from human bone marrow encoding a protein exhibiting homology to the ATP1gamma1/PLM/MAT8 family of transmembrane proteins". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1517 (2): 307–10. doi:10.1016/S0167-4781(00)00251-7. PMID11342114.
Shimada Y, Hashimoto Y, Kan T, Kawamura J, Okumura T, Soma T, Kondo K, Teratani N, Watanabe G, Ino Y, Sakamoto M, Hirohashi S, Imamura M (2004). "Prognostic significance of dysadherin expression in esophageal squamous cell carcinoma". Oncology. 67 (1): 73–80. doi:10.1159/000080289. PMID15459499.
Wu D, Qiao Y, Kristensen GB, Li S, Troen G, Holm R, Nesland JM, Suo Z (2005). "Prognostic significance of dysadherin expression in cervical squamous cell carcinoma". Pathology Oncology Research. 10 (4): 212–8. doi:10.1007/BF03033763. PMID15619642.
Nishizawa A, Nakanishi Y, Yoshimura K, Sasajima Y, Yamazaki N, Yamamoto A, Hanada K, Kanai Y, Hirohashi S (April 2005). "Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma: immunohistochemical analysis of 115 patients". Cancer. 103 (8): 1693–700. doi:10.1002/cncr.20984. PMID15751018.
Batistatou A, Makrydimas G, Zagorianakou N, Zagorianakou P, Nakanishi Y, Agnantis NJ, Hirohashi S, Charalabopoulos K (2007). "Expression of dysadherin and E-cadherin in trophoblastic tissue in normal and abnormal pregnancies". Placenta. 28 (5–6): 590–2. doi:10.1016/j.placenta.2006.09.004. PMID17084448.
