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
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 31,032,722 bp[2] End 31,042,481 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • actin binding • ion channel activity • sodium channel regulator activity • cadherin binding • GO:0001948 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: 31.03 – 31.04 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]

References

1. GRCh38: Ensembl release 89: ENSG00000089327 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000009687 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: FXYD5 FXYD domain containing ion transport regulator 5".
6. Tokhtaeva E, Sun H, Deiss-Yehiely N, Wen Y, Soni PN, Gabrielli NM, Marcus EA, Ridge KM, Sachs G, Vazquez-Levin M, Sznajder JI, Vagin O, Dada LA (June 2016). "The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits". Journal of Cell Science. 129 (12): 2394–406. doi:10.1242/jcs.186148. PMC 4920254. PMID 27142834.
7. Marshall DJ, Harried SS, Murphy JL, Hall CA, Shekhani MS, Pain C, Lyons CA, Chillemi A, Malavasi F, Pearce HL, Thorson JS, Prudent JR (October 2016). "Extracellular Antibody Drug Conjugates Exploiting the Proximity of Two Proteins". Molecular Therapy. 24 (10): 1760–1770. doi:10.1038/mt.2016.119. PMC 5112037. PMID 27434591.

Further reading

• Nam JS, Hirohashi S, Wakefield LM (October 2007). "Dysadherin: a new player in cancer progression". Cancer Letters. 255 (2): 161–9. doi:10.1016/j.canlet.2007.02.018. PMC 2094007. PMID 17442482.
• Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (September 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
• 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. PMID 10950925.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• 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. PMID 11342114.
• Ino Y, Gotoh M, Sakamoto M, Tsukagoshi K, Hirohashi S (January 2002). "Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis". Proceedings of the National Academy of Sciences of the United States of America. 99 (1): 365–70. doi:10.1073/pnas.012425299. PMC 117566. PMID 11756660.
• Sato H, Ino Y, Miura A, Abe Y, Sakai H, Ito K, Hirohashi S (September 2003). "Dysadherin: expression and clinical significance in thyroid carcinoma". The Journal of Clinical Endocrinology and Metabolism. 88 (9): 4407–12. doi:10.1210/jc.2002-021757. PMID 12970317.
• Shimada Y, Yamasaki S, Hashimoto Y, Ito T, Kawamura J, Soma T, Ino Y, Nakanishi Y, Sakamoto M, Hirohashi S, Imamura M (April 2004). "Clinical significance of dysadherin expression in gastric cancer patients". Clinical Cancer Research. 10 (8): 2818–23. doi:10.1158/1078-0432.CCR-0633-03. PMID 15102690.
• 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. PMID 15459499.
• Shimamura T, Yasuda J, Ino Y, Gotoh M, Tsuchiya A, Nakajima A, Sakamoto M, Kanai Y, Hirohashi S (October 2004). "Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells". Cancer Research. 64 (19): 6989–95. doi:10.1158/0008-5472.CAN-04-1166. PMID 15466191.
• 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. PMID 15619642.
• 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. PMID 15751018.
• Batistatou A, Scopa CD, Ravazoula P, Nakanishi Y, Peschos D, Agnantis NJ, Hirohashi S, Charalabopoulos KA (December 2005). "Involvement of dysadherin and E-cadherin in the development of testicular tumours". British Journal of Cancer. 93 (12): 1382–7. doi:10.1038/sj.bjc.6602880. PMC 2361540. PMID 16333245.
• 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. PMID 17084448.
• Batistatou A, Peschos D, Tsanou H, Charalabopoulos A, Nakanishi Y, Hirohashi S, Agnantis NJ, Charalabopoulos K (May 2007). "In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin". British Journal of Cancer. 96 (9): 1404–8. doi:10.1038/sj.bjc.6603743. PMC 2360179. PMID 17437014.