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Gene Review

Fxyd4  -  FXYD domain-containing ion transport...

Rattus norvegicus

Synonyms: CHIF, Channel-inducing factor, Corticosteroid-induced protein
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Disease relevance of Fxyd4


Psychiatry related information on Fxyd4


High impact information on Fxyd4

  • This is caused by corticosteroid-induced enhanced activities and protein expression of transport processes driving bicarbonate excretion in the biliary epithelium [5].
  • In contrast to gamma(a) and gamma(b), which both decrease the apparent Na+ affinity of the Na,K-pump, CHIF significantly increases the Na+ affinity and decreases the apparent K+ affinity due to an increased Na+ competition at external binding sites [6].
  • Xenopus laevis oocytes injected with cRNA synthesized from this clone, designated CHIF (channel-inducing factor), express a K(+)-specific channel activity [7].
  • Recently, we showed that supplementation with nitric oxide (NO) via donor nitroglycerin (NG) alleviated the ovariectomy and corticosteroid-induced bone loss in rats [8].
  • Immunolocalization experiments demonstrate mutually exclusive expression of CHIF and gamma in different nephron segments [9].

Chemical compound and disease context of Fxyd4


Biological context of Fxyd4


Anatomical context of Fxyd4

  • The data are consistent with the possibility that CHIF is a member of a family of transmembrane regulators capable of activating endogenous oocyte transport proteins [7].
  • CHIF is selectively present in the distal parts of the nephron (medullary and papillary collecting ducts and end portions of cortical collecting tubule) and in the epithelial cells of the distal colon [1].
  • In summary, CHIF mRNA is selectively expressed in the medullary collecting duct of the kidney and in the epithelium of the distal colon; its expression varies differently in these two target tissues after alterations in corticosteroid status, potassium depletion, and metabolic acidosis [1].
  • No expression of CHIF was found in renal proximal tubule, loop of Henle and distal tubule, proximal colon, small intestine, lung, choroid plexus, salivary glands, or brain [1].
  • Measurements of Na-K-ATPase using isolated membranes show similar but smaller effects of CHIF on K'(Na), whereas K'(K) and K'(ATP) are unaffected [9].

Associations of Fxyd4 with chemical compounds


Other interactions of Fxyd4


Analytical, diagnostic and therapeutic context of Fxyd4

  • To find a possible physiological function of the constitutively open KCNQ1/CHIF complex, the precise localization of KCNQ1 and CHIF in distal colon and kidney from control and salt-depleted rats was determined by confocal microscopy [12].
  • We have studied the tissue specificity of CHIF expression in rat by in situ hybridization [1].
  • In contrast, a most significant increase in CHIF mRNA expression (250% of baseline) was noted in the colon after 24 to 48 hours of reperfusion [2].
  • The expression of CHIF and ROMK was examined by Northern blot hybridization in renal cortex, medulla, and papilla and in the colon [2].
  • Confocal immunocytochemistry demonstrates that CHIF is present in the basolateral membrane of CD principal cells and distal colon surface cells, with occasional intracellular staining [14].


  1. Cellular localization and regulation of CHIF in kidney and colon. Capurro, C., Coutry, N., Bonvalet, J.P., Escoubet, B., Garty, H., Farman, N. Am. J. Physiol. (1996) [Pubmed]
  2. Regulation of ROMK and channel-inducing factor (CHIF) in acute renal failure due to ischemic reperfusion injury. Gimelreich, D., Popovtzer, M.M., Wald, H., Pizov, G., Berlatzky, Y., Rubinger, D. Kidney Int. (2001) [Pubmed]
  3. Sensitized splenocytes result in deleterious cytokine cascade and hyperinflammatory response in rats with Pneumocystis pneumonia despite the presence of corticosteroids. Thullen, T.D., Ashbaugh, A.D., Daly, K.R., Linke, M.J., Steele, P.E., Walzer, P.D. Infect. Immun. (2004) [Pubmed]
  4. Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders. Haynes, L.E., Griffiths, M.R., Hyde, R.E., Barber, D.J., Mitchell, I.J. Neuroscience (2001) [Pubmed]
  5. Corticosteroids modulate the secretory processes of the rat intrahepatic biliary epithelium. Alvaro, D., Gigliozzi, A., Marucci, L., Alpini, G., Barbaro, B., Monterubbianesi, R., Minetola, L., Mancino, M.G., Medina, J.F., Attili, A.F., Benedetti, A. Gastroenterology (2002) [Pubmed]
  6. CHIF, a member of the FXYD protein family, is a regulator of Na,K-ATPase distinct from the gamma-subunit. Béguin, P., Crambert, G., Guennoun, S., Garty, H., Horisberger, J.D., Geering, K. EMBO J. (2001) [Pubmed]
  7. A corticosteroid-induced gene expressing an "IsK-like" K+ channel activity in Xenopus oocytes. Attali, B., Latter, H., Rachamim, N., Garty, H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Frequency-dependent effect of nitric oxide donor nitroglycerin on bone. Wimalawansa, S., Chapa, T., Fang, L., Yallampalli, C., Simmons, D., Wimalawansa, S. J. Bone Miner. Res. (2000) [Pubmed]
  9. A functional interaction between CHIF and Na-K-ATPase: implication for regulation by FXYD proteins. Garty, H., Lindzen, M., Scanzano, R., Aizman, R., Füzesi, M., Goldshleger, R., Farman, N., Blostein, R., Karlish, S.J. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  10. Suppression of corticosteroid-induced atrophy and telangiectasia with vitamin A. Rist, T., Ruggles, C.W., Ryan, M.E., Garcia, R.L., Osborne, D. Archives of dermatology. (1978) [Pubmed]
  11. Effect of heparin on tendon degeneration: an experimental study on rats. Tatari, H., Koşay, C., Baran, O., Ozcan, O., Ozer, E., Ulukuş, C. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. (2001) [Pubmed]
  12. The corticosteroid hormone induced factor: a new modulator of KCNQ1 channels? Jespersen, T., Grunnet, M., Rasmussen, H.B., Jørgensen, N.B., Jensen, H.S., Angelo, K., Olesen, S.P., Klaerke, D.A. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  13. Insulin-like growth factor-I reverses the impairment of wound healing induced by corticosteroids in rats. Suh, D.Y., Hunt, T.K., Spencer, E.M. Endocrinology (1992) [Pubmed]
  14. Membrane topology and immunolocalization of CHIF in kidney and intestine. Shi, H., Levy-Holzman, R., Cluzeaud, F., Farman, N., Garty, H. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  15. Beta-adrenergic agonists inhibit corticosteroid-induced apoptosis of airway epithelial cells. Tse, R., Marroquin, B.A., Dorscheid, D.R., White, S.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  16. Detailed examination of the mechanism and site of action of progesterone and corticosteroids in the regulation of gonadotropin secretion: hypothalamic gonadotropin-releasing hormone and catecholamine involvement. Brann, D.W., Mahesh, V.B. Biol. Reprod. (1991) [Pubmed]
  17. Prevention of corticosteroid-induced bone loss with alendronate. Wimalawansa, S.J., Simmons, D.J. Proc. Soc. Exp. Biol. Med. (1998) [Pubmed]
  18. In vivo effects of systemic insulin-like growth factor-I alone and complexed with insulin-like growth factor binding protein-3 on corticosteroid suppressed wounds. Hamon, G.A., Hunt, T.K., Spencer, E.M. Growth Regul. (1993) [Pubmed]
  19. Growth hormone does not prevent corticosteroid-induced changes in rat diaphragm structure and function. Petrof, B.J., Gottfried, S.B., Eby, J., Lamanca, J., Levine, S. J. Appl. Physiol. (1995) [Pubmed]
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