FXYD5


FXYD domain-containing ion transport regulator 5 also named dysadherin or RIC is a protein that in humans is encoded by the FXYD5 gene.

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. FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1, FXYD2, FXYD3, FXYD4, and FXYD5 have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members, 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.
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 is a protein that is highly affected by silencing dysadherin expression. Dysadherin interferes with cell adhesion via beta1 subunit interactions. Dysdaherin is a target for an extracellular antibody drug conjugate where the antibody to dysadherin is attached to a cardiac glycoside.

Clinical significance

Dysadherin has been found to be a marker for metastatic cancers and found up-regulated in multiple cancer types.