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SLC24A3 Membrane Protein Introduction

Introduction of SLC24A3

SLC24A3 (NCKX3) is a protein that widely exists in human. SLC24A3 encodes a protein of 644 amino acids that displays a high level of sequence identity to the other family members in the hydrophobic regions surrounding the “a-repeat” sequences. This sequence is thought to form the ion-binding pocket for transport. As anticipated from this sequence similarity, SLC24A3 displays K+-dependent Na+/Ca2+ exchanger activity when assayed in heterologous expression systems. The N-terminal region of SLC24A3 increases functional activity at least 10-fold and may represent a cleavable signal sequence. SLC24A3 transcripts are most abundant in the brain, with highest levels in selected thalamic nuclei, in hippocampal CA1 neurons, and in layer IV of the cerebral cortex. Many other tissues also express SLC24A3 at lower levels, but it is abundant in smooth muscle.

Basic Information of SLC24A3
Protein Name Solute carrier family 24 member 3
Gene Name SLC24A3
Aliases Na(+)/K(+)/Ca(2+)-exchange protein 3(NCKX3), Sodium/potassium/calcium exchanger 3
Organism Homo sapiens (Human)
UniProt ID Q9HC58
Transmembrane Times 10
Length (aa) 644
Sequence MRPSGDEDRARRRRRRRRRRDLLLSQLCFLASVALLLWSLSSLREQKELDLMDLVGEDRKWMMARKLMQVNDTLTSEDAGLRNSKNCTEPALHEFPNDIFTNEDRRQGAVVLHVLCAIYMFYALAIVCDDFFVPSLEKICERLHLSEDVAGATFMAAGSSAPELFTSVIGVFITKGDVGVGTIVGSAVFNILCIIGVCGLFAGQVVALSSWCLLRDSIYYTLSVIALIVFIYDEKVSWWESLVLVLMYLIYIVIMKYNACIHQCFERRTKGAGNMVNGLANNAEIDDSSNCDATVVLLKKANFHRKASVIMVDELLSAYPHQLSFSEAGLRIMITSHFPPKTRLSMASRMLINERQRLINSRAYTNGESEVAIKIPIKHTVENGTGPSSAPDRGVNGTRRDDVVAEAGNETENENEDNENDEEEEEDEDDDEGPYTPFDTPSGKLETVKWAFTWPLSFVLYFTVPNCNKPRWEKWFMVTFASSTLWIAAFSYMMVWMVTIIGYTLGIPDVIMGITFLAAGTSVPDCMASLIVARQGMGDMAVSNSIGSNVFDILIGLGLPWALQTLAVDYGSYIRLNSRGLIYSVGLLLASVFVTVFGVHLNKWQLDKKLGCGCLLLYGVFLCFSIMTEFNVFTFVNLPMCGDH

Function of SLC24A3 Membrane Protein

SLC24A3 belongs to the NCKX family, which plays a critical role in Ca(2+) homeostasis in a wide variety of biological processes such as vision, olfaction, enamel formation, Melanocortin-4-receptor-dependent satiety, and skin pigmentation. It has been revealed that SLC24A3 mainly functions to transport one (Ca2+ + K+) in exchange for four Na+. So, it can influence calcium channel and symporter activity. SLC24A3 also regulates calcium ion, potassium ion and sodium ion binding in the physiological processes. Numerous biological processes, like cellular calcium ion homeostasis and ion transport, are also under the direction of SLC24A3. Depletion of the SLC24A3 gene in a KO mouse model showed loss of bone mineral contents and increased plasma parathyroid hormone, suggesting that SLC24A3 plays a role in regulating calcium homeostasis.

Role of SLC24A3 exchangers in mast cells. Fig.1 Role of SLC24A3 exchangers in mast cells. (Aneiros, 2005)

Application of SLC24A3 Membrane Protein in Literature

  1. Kraev A., et al. Molecular cloning of a third member of the potassium-dependent sodium-calcium exchanger gene family, NCKX3. J Biol Chem. 2001, 276(25): 23161-72. PubMed ID: 11294880

    This article concludes the identification and characterization of NCKX3 (SLC24A3). Their findings expand the K(+)-dependent Na(+)/Ca(2+) exchanger family and show that the transporter has a more important role in cellular Ca(2+) handling than appreciated.

  2. Visser F., et al. Exchangers NCKX2, NCKX3, and NCKX4: identification of Thr-551 as a key residue in defining the apparent K(+) affinity of NCKX2. J Biol Chem. 2007, 282(7): 4453-62. PubMed ID: 17172467

    This article provides us with information about the structure and function of NCKX proteins. It helps us understand those proteins’ roles in neuronal Ca(2+) signaling.

  3. Jalloul A.H., et al. Cation dependencies and turnover rates of the human K+-dependent Na+-Ca2+ exchangers NCKX1, NCKX2, NCKX3, and NCKX4. Cell Calcium. 2016, 59(1): 1-11. PubMed ID: 26631410

    This article shows that there are no significant differences in the function of all NCKX isoforms. So, the variation in the specific expression pattern of these exchangers is still unknown clearly.

  4. Yang H., et al. Distinct expression of the calcium exchangers, NCKX3 and NCX1, and their regulation by steroid in the human endometrium during the menstrual cycle. Reprod Sci. 2011, 18(6): 577-85. PubMed ID: 21321244

    These results indicate that NCKX3 is expressed within the human endometrium at the transcriptional and translational levels. Its expression level appears to be controlled by E2 during the human menstrual cycle.

  5. Lee J.Y., et al. Ionic selectivity of NCKX2, NCKX3, and NCKX4 for monovalent cations at K+-binding site. Ann N Y Acad Sci. 2007, 1099: 166-70. PubMed ID: 17446453

    This article presents three isoforms of NCKX family, NCKX2, NCKX3, and NCKX4. The relative potency of Cs+ and NH4+ in regulating NCKX2 is significantly better than those for NCKX3 and NCKX4, which means that the selectivity of NCKX2 for K+ is the weakest.

SLC24A3 Preparation Options

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Reference

  1. Aneiros E, et al. (2005). Modulation of Ca2+ signaling by Na+/Ca2+ exchangers in mast cells. J Immunol. 174(1): 119-30.

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