7x1g

Structural highlights

Disease

S4A11_HUMAN Corneal dystrophy-perceptive deafness syndrome;Fuchs endothelial corneal dystrophy;Congenital hereditary endothelial dystrophy type II. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

S4A11_HUMAN Multifunctional transporter with an impact in cell morphology and differentiation. In the presence of borate B(OH)4(-), acts as a voltage-dependent electrogenic Na(+)-coupled B(OH)4(-) cotransporter controlling boron homeostasis (PubMed:15525507). At early stages of stem cell differentiation, participates in synergy with ITGA5-ITGB1 and ITGAV-ITGB3 integrins and BMPR1A to promote cell adhesion and contractility that drives differentiation toward osteogenic commitment while inhibiting adipogenesis (By similarity). In the absence of B(OH)4(-), acts as a Na(+)-coupled OH(-) or H(+) permeable channel with implications in cellular redox balance (PubMed:15525507, PubMed:28642546). Regulates the oxidative stress response in corneal endothelium by enhancing antioxidant defenses and protecting cells from reactive oxygen species (PubMed:28642546). In response to hypo-osmotic challenge, also acts as water permeable channel at the basolateral cell membrane of corneal endothelial cells and facilitates transendothelial fluid reabsorption in the aqueous humor (PubMed:31273259, PubMed:25007886, PubMed:23813972). In the presence of ammonia, acts as an electrogenic NH3/H(+) cotransporter and may play a role in ammonia transport and reabsorption in renal Henle's loop epithelium (PubMed:27581649).[UniProtKB:A2AJN7]^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Park M, Li Q, Shcheynikov N, Zeng W, Muallem S. NaBC1 is a ubiquitous electrogenic Na+ -coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation. Mol Cell. 2004 Nov 5;16(3):331-41. PMID:15525507 doi:10.1016/j.molcel.2004.09.030
2. ↑ Vilas GL, Loganathan SK, Liu J, Riau AK, Young JD, Mehta JS, Vithana EN, Casey JR. Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases. Hum Mol Genet. 2013 Nov 15;22(22):4579-90. PMID:23813972 doi:10.1093/hmg/ddt307
3. ↑ Soumittra N, Loganathan SK, Madhavan D, Ramprasad VL, Arokiasamy T, Sumathi S, Karthiyayini T, Rachapalli SR, Kumaramanickavel G, Casey JR, Rajagopal R. Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy. J Hum Genet. 2014 Aug;59(8):444-53. PMID:25007886 doi:10.1038/jhg.2014.55
4. ↑ Kao L, Azimov R, Shao XM, Frausto RF, Abuladze N, Newman D, Aldave AJ, Kurtz I. Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants. Am J Physiol Cell Physiol. 2016 Nov 1;311(5):C820-C830. PMID:27581649 doi:10.1152/ajpcell.00233.2016
5. ↑ Guha S, Chaurasia S, Ramachandran C, Roy S. SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress. Sci Rep. 2017 Jun 22;7(1):4074. PMID:28642546 doi:10.1038/s41598-017-03654-4
6. ↑ Malhotra D, Loganathan SK, Chiu AM, Lukowski CM, Casey JR. Human Corneal Expression of SLC4A11, a Gene Mutated in Endothelial Corneal Dystrophies. Sci Rep. 2019 Jul 4;9(1):9681. PMID:31273259 doi:10.1038/s41598-019-46094-y