SLC24A4 Membrane Protein Introduction

Introduction of SLC24A4

SLC24A4, also known as NCKX4, is a protein that widely exists in human. SLC24A4 is an important member of SLC24A family, which has a number of proteins functioning as Na⁺/Ca²⁺ exchangers. It has been shown that SLC24A4 plays an important role in the olfactory function and in tooth enamel formation. Mutations in SLC24A4 will bring about amelogenesis imperfecta.

Basic Information of SLC24A4
Protein Name	Solute carrier family 24 member 4
Gene Name	SLC24A4
Aliases	Na(+)/K(+)/Ca(2+)-exchange protein 4(NCKX4), Sodium/potassium/calcium exchanger 4
Organism	Homo sapiens (Human)
UniProt ID	Q8NFF2
Transmembrane Times	10
Length (aa)	622
Sequence	MALRGTLRPLKVRRRREMLPQQVGFVCAVLALVCCASGLFGSLGHKTASASKRVLPDTWRNRKLMAPVNGTQTAKNCTDPAIHEFPTDLFSNKERQHGAVLLHILGALYMFYALAIVCDDFFVPSLEKICERLHLSEDVAGATFMAAGSSTPELFASVIGVFITHGDVGVGTIVGSAVFNILCIIGVCGLFAGQVVRLTWWAVCRDSVYYTISVIVLIVFIYDEQIVWWEGLVLIILYVFYILIMKYNVKMQAFFTVKQKSIANGNPVNSELEAGNDFYDGSYDDPSVPLLGQVKEKPQYGKNPVVMVDEIMSSSPPKFTFPEAGLRIMITNKFGPRTRLRMASRIIINERQRLINSANGVSSKPLQNGRHENIENGNVPVENPEDPQQNQEQQPPPQPPPPEPEPVEADFLSPFSVPEARGDKVKWVFTWPLIFLLCVTIPNCSKPRWEKFFMVTFITATLWIAVFSYIMVWLVTIIGYTLGIPDVIMGITFLAAGTSVPDCMASLIVARQGLGDMAVSNTIGSNVFDILVGLGVPWGLQTMVVNYGSTVKINSRGLVYSVVLLLGSVALTVLGIHLNKWRLDRKLGVYVLVLYAIFLCFSIMIEFNVFTFVNLPMCREDD

Function of SLC24A4 Membrane Protein

As a member of solute carrier family 24, SLC24A4 is involved in potassium-dependent sodium/calcium exchange and transport. It also controls the rapid response termination and proper regulation of adaptation in olfactory sensory neurons (OSNs), which subsequently influences how odor information is encoded and perceived. Research shows that it may play a role in calcium transport during amelogenesis. It is also documented that loss of SCL24A4 in mouse cones will reduce the ability of these cells to respond to fast and rapidly changing light stimuli and to operate in bright light. Mutations in SCL24A4 gene are recently found to cause a similar type of enamel hypoplasia in people. Its function covers amelogenesis, cellular calcium ion homeostasis, ion transport and responding to stimulus, as well as the sensory perception of smell.

Fig.1 Role of NCKX3 exchangers in mast cells. (Zufall, 2012)

Application of SLC24A4 Membrane Protein in Literature

Li X.F., et al. Molecular cloning of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4. J Biol Chem. 2002, 277(50): 48410-7. PubMed ID: 12379639

The article finds that NCKX4 protein participates in potassium-dependent sodium-calcium exchanger activity. The discovery of NCKX4 completes the mammalian potassium-dependent sodium-calcium exchanger gene family.
Stephan A.B., et al. The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response. Nat Neurosci. 2011, 15(1): 131-7. PubMed ID: 22057188

Their results establish the role of NCKX4 in shaping olfactory responses and suggest that rapid response termination and proper adaptation of peripheral sensory receptor cells tune the sensory system for optimal perception.
Hu P., et al. Expression of the sodium/calcium/potassium exchanger, NCKX4, in ameloblasts. Cells Tissues Organs. 2012, 196(6): 501-9. PubMed ID: 22677781

These data suggest that NCKX4 might be an important regulator of Ca(2+) transport during amelogenesis.
Li X.F. and Lytton J. An essential role for the K⁺-dependent Na⁺/Ca²⁺-exchanger, NCKX4, in melanocortin-4-receptor-dependent satiety. J Biol Chem. 2014, 289(37): 25445-59. PubMed ID: 25096581

The findings of this article highlight a novel pathway that potentially could be exploited to develop much needed new therapeutics to tackle eating disorders and obesity.
Vinberg F., et al. The Na⁺/Ca²⁺, K⁺ exchanger NCKX4 is required for efficient cone-mediated vision. Elife. 2017, 6. pii: e24550. PubMed ID: 28650316

The authors show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2. NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca²⁺ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promote their survival.

SLC24A4 Preparation Options

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Reference

Zufall F. (2012). On the scent of mitochondrial calcium. Nat Neurosci. 15(5): 653-4.

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