FXYD5

FXYD domain-containing ion transport regulator 5 also named dysadherin (human) or RIC (mouse) is a protein that in humans is encoded by the FXYD5 gene.^[5]

FXYD5
Identifiers
Aliases	FXYD5, DYSAD, IWU1, KCT1, OIT2, PRO6241, RIC, HSPC113, FXYD domain containing ion transport regulator 5
External IDs	OMIM: 606669; MGI: 1201785; HomoloGene: 7458; GeneCards: FXYD5; OMA:FXYD5 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.12 Start 35,154,730 bp[1] End 35,169,881 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 30,732,147 bp[2] End 30,741,906 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte stromal cell of endometrium ectocervix spleen right lung ascending aorta Descending thoracic aorta canal of the cervix right coronary artery Top expressed in granulocyte tibiofemoral joint ankle blood endothelial cell of lymphatic vessel gastrula ankle joint thymus decidua spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function actin binding ion channel activity sodium channel regulator activity cadherin binding protein binding ion channel regulator activity Cellular component integral component of membrane integral component of plasma membrane membrane Biological process negative regulation of calcium-dependent cell-cell adhesion ion transmembrane transport microvillus assembly ion transport regulation of sodium ion transmembrane transporter activity regulation of ion transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 53827 18301 Ensembl ENSG00000089327 ENSMUSG00000009687 UniProt Q96DB9 P97808 RefSeq (mRNA) NM_001164605 NM_014164 NM_144779 NM_001320912 NM_001320913 NM_001111073 NM_001287213 NM_001287217 NM_008761 RefSeq (protein) NP_001158077 NP_001307841 NP_001307842 NP_054883 NP_659003 NP_001104543 NP_001274142 NP_001274146 NP_032787 Location (UCSC) Chr 19: 35.15 – 35.17 Mb Chr 7: 30.73 – 30.74 Mb PubMed search [3] [4]
Wikidata
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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 of 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] Dysadherin 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]