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SLC8A2 Membrane Protein Introduction

Introduction of SLC8A2

SLC8A2 (solute carrier family 8 member 2), also called Na+/Ca2+ exchanger 2 (NCX2), is encoded by SLC8A2 gene in human. Containing 10 exons, SLC8A2 gene is located on chromosome 19q13.32. Belonging to the Na+/Ca2+ exchanger family, SLC8A2 is predicted to have 10 transmembrane helices (10TM) with a diamond-shaped site for substrate binding, a cytoplasmic N and C termini. Notably, a large cytoplasmic loop containing two structurally homologous Ca2+ binding domains CBD1 and CBD2 is located in the architecture of SLC8A2, forming the calcium regulatory exchanger loop. SLC8A2 is abundant in the normal brain with specific brain regions, among which expression is highest in the amygdala, cerebellum, and caudate nucleus, with intermediate levels in all other regions. Recent studies showed that SLC8A2 was also expressed in the basolateral membrane of the distal nephron.

Basic Information of SLC8A2
Protein Name Sodium/calcium exchanger 2
Gene Name SLC8A2
Aliases NCX2, KIAA1087
Organism Homo sapiens (Human)
UniProt ID Q9UPR5
Transmembrane Times 10
Length (aa) 921
Sequence MAPLALVGVTLLLAAPPCSGAATPTPSLPPPPANDSDTSTGGCQGSYRCQPGVLLPVWEPDDPSLGDKAARAVVYFVAMVYMFLGVSIIADRFMAAIEVITSKEKEITITKANGETSVGTVRIWNETVSNLTLMALGSSAPEILLSVIEVCGHNFQAGELGPGTIVGSAAFNMFVVIAVCIYVIPAGESRKIKHLRVFFVTASWSIFAYVWLYLILAVFSPGVVQVWEALLTLVFFPVCVVFAWMADKRLLFYKYVYKRYRTDPRSGIIIGAEGDPPKSIELDGTFVGAEAPGELGGLGPGPAEARELDASRREVIQILKDLKQKHPDKDLEQLVGIANYYALLHQQKSRAFYRIQATRLMTGAGNVLRRHAADASRRAAPAEGAGEDEDDGASRIFFEPSLYHCLENCGSVLLSVTCQGGEGNSTFYVDYRTEDGSAKAGSDYEYSEGTLVFKPGETQKELRIGIIDDDIFEEDEHFFVRLLNLRVGDAQGMFEPDGGGRPKGRLVAPLLATVTILDDDHAGIFSFQDRLLHVSECMGTVDVRVVRSSGARGTVRLPYRTVDGTARGGGVHYEDACGELEFGDDETMKTLQVKIVDDEEYEKKDNFFIELGQPQWLKRGISALLLNQGDGDRKLTAEEEEARRIAEMGKPVLGENCRLEVIIEESYDFKNTVDKLIKKTNLALVIGTHSWREQFLEAITVSAGDEEEEEDGSREERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFGVSILVIGLLTALIGDLASHFGCTVGLKDSVNAVVFVALGTSIPDTFASKVAALQDQCADASIGNVTGSNAVNVFLGLGVAWSVAAVYWAVQGRPFEVRTGTLAFSVTLFTVFAFVGIAVLLYRRRPHIGGELGGPRGPKLATTALFLGLWLLYILFASLEAYCHIRGF

Function of SLC8A2 Membrane Protein

SLC8A2 transporter mediates the exchange of Na+ and Ca2+ across the membrane by electrogenical membrane potential and transmembrane gradients, contributing to intracellular Ca2+ homeostasis in excitable cells. This rapid SLC8A2-mediated Ca2+ transport during excitation contraction can effectively prevent overloading of intracellular Ca2+ stores. In the brain, SLC8A2 is responsible for the rapid decrease of cytoplasmic Ca2+ levels back to baseline after neuronal activation and thereby contributes to modulate synaptic plasticity, learning, and memory. In the kidney, functional inhibition of SLC8A2 causes natriuresis and hypercalciuria, suggesting that SLC8A2 plays significant roles in renal Na+ and Ca2+ reabsorption. In the gastrointestinal system, SLC8A2 plays important roles in the motility of the gastric fundus, ileum and distal colon, responsible for the development of diarrhea. Moreover, it is documented that the transcriptional silencing of SLC8A2 in gliomas is significantly regulated by DNA methylation and SLC8A2 is not present at any significant levels in gliomas, suggesting that SLC8A2 might be a tumor suppressor gene involved in gliomas genesis and tumor progression.

Structure of NCX. Fig.1 Structure of NCX. (Giladi, 2016)

Application of SLC8A2 Membrane Protein in Literature

  1. Qu M., et al. The candidate tumor suppressor gene SLC8A2 inhibits invasion, angiogenesis, and growth of glioblastoma. Molecules and cells. 2017, 40(10): 761. PubMed ID: 29047259

    The authors demonstrated that SLC8A2 can inhibit the tumorigenicity of U87MG in nude mice. With no effect on cell proliferation or cell cycle, overexpression of SLC8A2 impaired the invasion and migration of U87MG cells most likely through inactivating the ERK 1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of NF-κB. So SLC8A2 may be a tumor suppressor gene and inhibit invasion, angiogenesis, and growth of glioblastoma.

  2. Cheng P.C., et al. Na+/Ca2+ exchanger 2 (NCX2) in the circadian clock of the rat suprachiasmatic nucleus: colocalization with neuropeptides and daily profiles of gene expression and protein levels. Chinese Journal of Physiology. 2017, 60(4): 215-225. PubMed ID: 28847141

    This article investigated the colocalization of NCX2 with neuropeptides and NCX2 expression profiles in mRNA and protein levels. They found that NCX2 was mainly located in the retinorecipient ventral suprachiasmatic nucleus (SCN), with colocalization with vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and VIP/GRP, but not with arginine vasopressin (AVP) in the dorsal SCN, suggesting a role of NCX2 in the regulation of the release of VIP and GRP.

  3. Nishiyama K., et al. Na+/Ca2+ exchanger contributes to stool transport in mice with experimental diarrhea. Journal of Veterinary Medical Science. 2017, 79(2): 403-411. PubMed ID: 27928109

    The authors used NCX1 and NCX2 heterozygote knockout mice (HET) to investigate the role of NCX in a mouse model of diarrhea induced by the drug (magnesium sulfate, 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2)). They demonstrated that NCX2 had important roles in the development of diarrhea.

  4. Gotoh Y., et al. Genetic knockout and pharmacologic inhibition of NCX2 cause natriuresis and hypercalciuria. Biochemical and biophysical research communications. 2015, 456(2): 670-675. PubMed ID: 25498502

    The authors used NCX1- and NCX2-heterozygote knockout mice (KO) and their double KO, and NCX1/NCX2 inhibitors to reveal that functional inhibition of NCX2 can cause natriuresis, and further hypercalciuria, suggesting its significance in Na(+) and Ca(2+) reabsorption of the kidney.

  5. Giladi M., et al. Structure-functional basis of ion transport in sodium-calcium exchanger (NCX) proteins. International journal of molecular sciences. 2016, 17(11): 1949. PubMed ID: 27879668

    This review summarized various data from the X-ray crystallography, molecular dynamics simulations, hydrogen-deuterium exchange mass-spectrometry (HDX-MS), and ion-flux analyses of mutants and demonstrated that the conserved α₁ and α₂ repeats at ion-coordinating residues of NCX were involved in transport activities. The review significantly provided the structure-functional basis of NCX and improved our understanding of ion transport mechanisms in NCX and similar proteins.

SLC8A2 Preparation Options

To obtain the soluble and functional target protein, Creative Biolabs develops the versatile Magic™ membrane protein production platform to provide many flexible options, from which you can always find the best match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC8A2 antibody development services.


Over the years, Creative Biolabs has successfully generated massive functional membrane proteins for our customers. We are glad to provide one-stop, custom-oriented service packages regarding a variety of membrane protein targets. Please feel free to contact us for more information when you need.

Reference

  1. Giladi M, et al. (2016). Structure-functional basis of ion transport in sodium-calcium exchanger (NCX) proteins. International journal of molecular sciences. 2016, 17(11), 1949.

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