KCNS2 Membrane Protein Introduction

Introduction of KCNS2

KCNS2, potassium voltage-gated channel subfamily S member 2 is a protein that in humans is encoded by the KCNS2 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit. This potassium channel subunit does not form functional channels by itself, but it can form functional heterotetrameric channels with KCNB1 and KCNB2 to modulate the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 and KCNB2.

Basic Information of KCNS2
Protein Name	Potassium voltage-gated channel subfamily S member 2
Gene Name	KCNS2
Aliases	Delayed-rectifier K(+) channel alpha subunit 2, Voltage-gated potassium channel subunit Kv9.2, KIAA1144
Organism	Homo sapiens (Human)
UniProt ID	Q9ULS6
Transmembrane Times	6
Length (aa)	477
Sequence	MTGQSLWDVSEANVEDGEIRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCVFSFSQEIEYWGINEFFIDSCCSYSYHGRKVEPEQEKWDEQSDQESTTSSFDEILAFYNDASKFDGQPLGNFRRQLWLALDNPGYSVLSRVFSILSILVVMGSIITMCLNSLPDFQIPDSQGNPGEDPRFEIVEHFGIAWFTFELVARFAVAPDFLKFFKNALNLIDLMSIVPFYITLVVNLVVESTPTLANLGRVAQVLRLMRIFRILKLARHSTGLRSLGATLKYSYKEVGLLLLYLSVGISIFSVVAYTIEKEENEGLATIPACWWWATVSMTTVGYGDVVPGTTAGKLTASACILAGILVVVLPITLIFNKFSHFYRRQKQLESAMRSCDFGDGMKEVPSVNLRDYYAHKVKSLMASLTNMSRSSPSELSLNDSLR

Function ofKCNS2 Membrane Protein

KCNS2 gene was identified and cloned in 1997, and it is located in the 8q22 region of the chromosome. It’s colocalized with Kv2.1 and/or Kv2.2 alpha subunits in several regions of the brain. Neither Kv9.1 nor Kv9.2 has K⁺ channel activity by themselves, but both modulate the activity of Kv2.1 and Kv2.2 channels by changing kinetics and levels of expression and by shifting the half-inactivation potential to more polarized values. In later researches, it has been reported that Kv9.2 mutations were identified in Essential Tremor, early-onset essential tremor, human Neuroblastoma, rat pulmonary arteries. They show the potential function of Kv9.2 in these diseases. In addition, Kv9.1 may have a functional role in neural proliferation. Also, mutations in Kv9.1 is associated with the development of Essential Tremor. Furthermore, it plays a critical role in HPV infection in rat, mainly in small pulmonary arteries.

Fig.1 Model 3D protein structure of KCNS2. (Liu, 2016)

Application of KCNS2 Membrane Protein in Literature

Smith P., et al. A Drosophila Model of Essential Tremor. Sci Rep. 2018, 8(1):7664. PubMed ID: 29769701

This article identified a mutation of KCNS2 in a family with Essential Tremor, and then validated the function in a drosophila model, and demonstrated KCNS2’s role in ET disease.
Liu X., et al. Identification of candidate genes for familial early-onset essential tremor. Eur J Hum Genet. 2016, 24(7):1009-15. PubMed ID: 26508575

This article identified candidate genes including KCNS2 (KV9.2), HAPLN4 (BRAL2) and USP46 which were highly expressed in the cerebellum and Purkinje cells, and influence function of the gamma-amino butyric acid (GABA)-ergic system.
Hu X.M., et al. The Tau-Induced Reduction of mRNA Levels of Kv Channels in Human Neuroblastoma SK-N-SH Cells. J Mol Neurosci. 2016, 58(2):306-11. PubMed ID: 26576773

This study showed the possible interaction of tau with Kv channels - the tau-mediated alteration of Kv channels could be involved in its action on neural proliferation.
Li X., et al. Overexpression of tau downregulated the mRNA levels of Kv channels and improved proliferation in N2A cells. PLoS One. 2015, 10(1): e0116628. PubMed ID: 25590133

This article showed that overexpression of tau declined the mRNA levels of Kv channels and related currents. The effects of tau overexpression on Kv channels provided an alternative explanation for low sensitivity to anti-cancer chemicals in some specific cancer tissues.
Davies A.R and Kozlowski R.Z. Kv channel subunit expression in rat pulmonary arteries. Lung. 2001, 179(3):147-61. PubMed ID: 11891605

This article identified and fully sequenced a rat Kv9.2 cDNA through investigating the expression of delayed rectifying (Kv) channel mRNA in rat main and small pulmonary arteries. It may play a role in HPV infection.

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Reference

Liu X, et al. (2016). Identification of candidate genes for familial early-onset essential tremor. Eur J Hum Genet. 24(7):1009-15.

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