SLC9C1 Membrane Protein Introduction

Introduction of SLC9C1

SLC9C1, the official full name is solute carrier family 9 member C1, it’s also known as SLC9A10 or NHE-10. It is encoded by the SLC9C1 gene in humans, which is conserved in chimpanzee, mouse, and dog. It has been reported that 113 organisms have orthologs with this gene. SLC9C1 belongs to solute carrier family 9 or sodium-hydrogen exchanger (NHE) family, and is biased expressed in testis, skin and is involved in male fertility and sperm motility.

Basic Information of SLC9C1
Protein Name	Sodium/hydrogen exchanger 10
Gene Name	SLC9C1
Aliases	Na(+)/H(+) exchanger 10, NHE-10, Solute carrier family 9 member 10, Solute carrier family 9 member C1, Sperm-specific Na(+)/H(+) exchanger, sNHE, SLC9A10
Organism	Homo sapiens (Human)
UniProt ID	Q4G0N8
Transmembrane Times	16
Length (aa)	1177
Sequence	MAGIFKEFFFSTEDLPEVILTLSLISSIGAFLNRHLEDFPIPVPVILFLLGCSFEVLSFTSSQVQRYANAIQWMSPDLFFRIFTPVVFFTTAFDMDTYMLQKLFWQILLISIPGFLVNYILVLWHLASVNQLLLKPTQWLLFSAILVSSDPMLTAAAIRDLGLSRSLISLINGESLMTSVISLITFTSIMDFDQRLQSKRNHTLAEEIVGGICSYIIASFLFGILSSKLIQFWMSTVFGDDVNHISLIFSILYLIFYICELVGMSGIFTLAIVGLLLNSTSFKAAIEETLLLEFWTFLSRIAFLMVFTFFGLLIPAHTYLYIEFVDIYYSLNIYLTLIVLRFLTLLLISPVLSRVGHEFSWRWIFIMVCSEMKGMPNINMALLLAYSDLYFGSDKEKSQILFHGVLVCLITLVVNRFILPVAVTILGLRDATSTKYKSVCCTFQHFQELTKSAASALKFDKDLANADWNMIEKAITLENPYMLNEEETTEHQKVKCPHCNKEIDEIFNTEAMELANRRLLSAQIASYQRQYRNEILSQSAVQVLVGAAESFGEKKGKCMSLDTIKNYSESQKTVTFARKLLLNWVYNTRKEKEGPSKYFFFRICHTIVFTEEFEHVGYLVILMNIFPFIISWISQLNVIYHSELKHTNYCFLTLYILEALLKIAAMRKDFFSHAWNIFELAITLIGILHVILIEIDTIKYIFNETEVIVFIKVVQFFRILRIFKLIAPKLLQIIDKRMSHQKTFWYGILKGYVQGEADIMTIIDQITSSKQIKQMLLKQVIRNMEHAIKELGYLEYDHPEIAVTVKTKEEINVMLNMATEILKAFGLKGIISKTEGAGINKLIMAKKKEVLDSQSIIRPLTVEEVLYHIPWLDKNKDYINFIQEKAKVVTFDCGNDIFEEGDEPKGIYIIISGMVKLEKSKPGLGIDQMVESKEKDFPIIDTDYMLSGEIIGEINCLTNEPMKYSATCKTVVETCFIPKTHLYDAFEQCSPLIKQKMWLKLGLAITARKIREHLSYEDWNYNMQLKLSNIYVVDIPMSTKTDIYDENLIYVILIHGAVEDCLLRKTYRAPFLIPITCHQIQSIEDFTKVVIIQTPINMKTFRRNIRKFVPKHKSYLTPGLIGSVGTLEEGIQEERNVKEDGAHSAATARSPQPCSLLGTKFNCKESPRINLRKVRKE

Function of SLC9C1 Membrane Protein

SLC9C1 is also known as solute carrier family 9 member 10 (NHE10) which belongs to sodium-hydrogen exchanger (NHE) family. It was identified to be biased expressed in testis and skin. SLC9C1 is required for male fertility and sperm motility as a sperm-specific plasmalemmal NHE. In 2008, a study found that SLC9C1 is highly expressed in osteoclasts in response to NF-kB signaling, indicating that SLC9C1 is involved in osteoclast differentiation and survival. Also, the expression of SLC9C1 is associated with Dent’s disease identified in a mouse model. In addition, the identified mutation of SLC9C1 may be associated with asthenozoospermia in humans. Furthermore, inhibition of NHEs can prevent sRANKL-promoted cellular fusion. And anti-SLC9C1 monoclonal antibody can be used to inhibit bone resorption for targeted bone disease therapy. For the role of SLC9C1 in sperm function and fertilization in mammals, it is the impaired cAMP synthesis which can reduce motility deficiency, rather than intracellular pH signaling.

Fig.1 Models of SLC9C1 gating by voltage and cAMP. (Windler, 2018)

Application of SLC9C1 Membrane Protein in Literature

Windler F., et al. The solute carrier SLC9C1 is a Na⁺/H⁺-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding. Nat Commun. 2018, 9(1): 2809. PubMed ID: 30022052

This article indicates that SLC9C1 is a phylogenetic chimaera which can combine the gating mechanism of ion channels and the ion-exchange mechanism of solute carriers. It can enable downstream signaling events through a rapid pH response.
Mine Y., et al. Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and an NHE10-specific monoclonal antibody. Cell Biol Int. 2015, 39(6): 696-709. PubMed ID: 25612314

This article shows that anti-NHE10 monoclonal antibody can be used to inhibit bone resorption for targeted bone disease therapy.
Fuster D.G. and Alexander R.T. Traditional and emerging roles for the SLC9 Na⁺/H⁺ exchangers. Pflugers Arch. 2014, 466(1): 61-76. PubMed ID: 24337822

This article introduces the functional roles of SLC9 sodium/hydrogen exchangers including SLC9C1.
Guggino S.E. Can we generate new hypotheses about Dent's disease from gene analysis of a mouse model? Exp Physiol. 2009, 94(2): 191-6. PubMed ID: 18931044

This article shows that the transcription level of SLC9C1 is affected in Dent's disease, an X-linked renal tubular disorder.
Lee S.H., et al. NHE10, an osteoclast-specific member of the Na⁺/H⁺ exchanger family, regulates osteoclast differentiation and survival. Biochem Biophys Res Commun. 2008, 369(2): 320-6. PubMed ID: 18269914

This article shows that SLC9C1 is required for osteoclast differentiation and survival.

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Reference

Windler F, et al. (2018). The solute carrier SLC9C1 is a Na⁺/H⁺-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding. Nat Commun. 9(1): 2809.

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