SLC9A4 Membrane Protein Introduction

Introduction of SLC9A4

Solute carrier family 9A4 (SLC9A4) is also known as sodium-hydrogen antiporter 4 (NHE-4) or sodium/hydrogen exchanger 4. It is encoded by the SLC9A4 gene in humans. SLC9A4 is biased expressed in stomach and kidney. The SLC9A4 gene is conserved in Rhesus monkey, chimpanzee, dog, mouse, rat, cow, chicken, and frog. It belongs to the solute carrier family 9, and functions as a Na⁺/H⁺ antiporter. SLC9A4 is involved in pH homeostasis, and signal transduction.

Basic Information of SLC9A4
Protein Name	Sodium/hydrogen exchanger 4
Gene Name	SLC9A4
Aliases	Na(+)/H(+) exchanger 4, NHE-4, Solute carrier family 9 member 4, NHE4
Organism	Homo sapiens (Human)
UniProt ID	Q6AI14
Transmembrane Times	10
Length (aa)	798
Sequence	MALQMFVTYSPWNCLLLLVALECSEASSDLNESANSTAQYASNAWFAAASSEPEEGISVFELDYDYVQIPYEVTLWILLASLAKIGFHLYHRLPGLMPESCLLILVGALVGGIIFGTDHKSPPVMDSSIYFLYLLPPIVLEGGYFMPTRPFFENIGSILWWAVLGALINALGIGLSLYLICQVKAFGLGDVNLLQNLLFGSLISAVDPVAVLAVFEEARVNEQLYMMIFGEALLNDGITVVLYNMLIAFTKMHKFEDIETVDILAGCARFIVVGLGGVLFGIVFGFISAFITRFTQNISAIEPLIVFMFSYLSYLAAETLYLSGILAITACAVTMKKYVEENVSQTSYTTIKYFMKMLSSVSETLIFIFMGVSTVGKNHEWNWAFICFTLAFCQIWRAISVFALFYISNQFRTFPFSIKDQCIIFYSGVRGAGSFSLAFLLPLSLFPRKKMFVTATLVVIYFTVFIQGITVGPLVRYLDVKKTNKKESINEELHIRLMDHLKAGIEDVCGHWSHYQVRDKFKKFDHRYLRKILIRKNLPKSSIVSLYKKLEMKQAIEMVETGILSSTAFSIPHQAQRIQGIKRLSPEDVESIRDILTSNMYQVRQRTLSYNKYNLKPQTSEKQAKEILIRRQNTLRESMRKGHSLPWGKPAGTKNIRYLSYPYGNPQSAGRDTRAAGFSDDDSSDPGSPSITFSACSRIGSLQKQEAQEIIPMKSLHRGRKAFSFGYQRNTSQEEYLGGVRRVALRPKPLFHAVDEEGESGGESEGKASLVEVRSRWTADHGHGRDHHRSHSPLLQKK

Function of SLC9A4 Membrane Protein

As a member of sodium-hydrogen exchanger (NHE) protein family, SLC9A4 mediates the sodium-ion transport by exchanging intracellular hydrogen ions to external sodium ions and plays an important role in cell pH regulation and cell volume. As a member of SLC9A family, SLC9A4 might be affected by clinical exposure to NSAIDs just like other family members and this will lead to transport modulation and barrier function. SLC9A4 is one of the major proton extruding system driven by a sodium ion gradient. It plays a critical role in signal transduction and plays a specialized role in rectifying cell volume in the kidney upon response to fluctuations of hyperosmolar-stimulated cell shrinkage. SLC9A4 is insensitive to ethylisopropylamiloride and amiloride. In addition, SLC9A4 can be activated by cell shrinkage in a sustained intracellular acidification dependent approach. It can also affect the potassium and proton exchange and sodium/proton exchange. SLC9A4 is also related to pediatric celiac disease.

Fig.1 Topology of SLC9A family. (Hendus-Altenburger, 2014)

Application of SLC9A4 Membrane Protein in Literature

Balasopoulou A., et al. Novel genetic risk variants for pediatric celiac disease. Hum Genomics. 2016, 10(1): 34. PubMed ID: 27836013

This article indicates that SLC9A4 is identified as a genomic variant in pediatric celiac disease by a next-generation sequencing approach.
Ismail N., et al. Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein. Int J Med Sci. 2015, 12(6): 468-77. PubMed ID: 26078707

This article shows that the enhanced expression levels of NHE1, 2 and 4 in the cervix can help to restore pH modulating, and this can prevent cervicovaginal complications related to menopause.
Karimi B., et al. Comparison of effect of sex hormone manipulation during neonatal period, on mRNA expression of Slc9a4, Nr3c2, Htr5b and Mas1 in hippocampus and frontal cortex of male and female rats. J Biol Regul Homeost Agents. 2013, 27(3): 869-74. PubMed ID: 24152851

This article indicates that SLC9A4 is up-regulated in the male hippocampus compared with other samples.
Gholami K., et al. Differential expression of Na⁺/H⁺-exchanger (NHE-1, 2, and 4) proteins and mRNA in rodent's uterus under sex steroid effect and at different phases of the oestrous cycle. Biomed Res Int. 2013, 840121. PubMed ID: 23509787

This article shows the different expression levels of sodium/hydrogen exchanger (NHE1, 2, 4) under different sex steroid treatment and at different estrous cycle phases.
Arena E.A., et al. Functional role of NHE4 as a pH regulator in rat and human colonic crypts. Am J Physiol Cell Physiol. 2012, 302(2): C412-8. PubMed ID: 22049213

This article demonstrates that SLC9A4 plays a critical role in keeping cellular pH homeostasis over a wide range of pH spectrum.

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Reference

Hendus-Altenburger R, et al. (2014). Structural dynamics and regulation of the mammalian SLC9A family of Na⁺/H⁺ exchangers. Curr Top Membr. 73: 69-148.

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