KCNH6 Membrane Protein Introduction

Introduction of KCNH6

KCNH6 is encoded by KCNH6 gene. It belongs to the ERG subfamily of voltage-gated potassium channels which has been extensively studied during the past few decades because it offers numerous possibilities for therapeutic applications. KCNH6 (ccErg2) is the main isoform of the Kv11 potassium channel family with relative transcript levels of 98.9% and 99.6% in crucian carp atrium and ventricle, respectively. Meanwhile, recent studies have identified that KCNH6 is associated with many diseases, such as Charcot-Marie-Tooth disease, Demyelinating, Type 1D and Charcot-Marie-Tooth disease, Axonal, Type 2F, which indicates KCNH6 could be a biomarker in the clinic.

Basic Information of KCNH6
Protein Name	Potassium voltage-gated channel subfamily H member 6
Gene Name	KCNH6
Aliases	ERG-2, ERG2, HERG2, Kv11.2, hERG-2,
Organism	Homo sapiens (Human)
UniProt ID	Q9H252
Transmembrane Times	7
Length (aa)	994
Sequence	MPVRRGHVAPQNTYLDTIIRKFEGQSRKFLIANAQMENCAIIYCNDGFCELFGYSRVEVMQQPCTCDFLTGPNTPSSAVSRLAQALLGAEECKVDILYYRKDASSFRCLVDVVPVKNEDGAVIMFILNFEDLAQLLAKCSSRSLSQRLLSQSFLGSEGSHGRPGGPGPGTGRGKYRTISQIPQFTLNFVEFNLEKHRSSSTTEIEIIAPHKVVERTQNVTEKVTQVLSLGADVLPEYKLQAPRIHRWTILHYSPFKAVWDWLILLLVIYTAVFTPYSAAFLLSDQDESRRGACSYTCSPLTVVDLIVDIMFVVDIVINFRTTYVNTNDEVVSHPRRIAVHYFKGWFLIDMVAAIPFDLLIFRTGSDETTTLIGLLKTARLLRLVRVARKLDRYSEYGAAVLFLLMCTFALIAHWLACIWYAIGNVERPYLEHKIGWLDSLGVQLGKRYNGSDPASGPSVQDKYVTALYFTFSSLTSVGFGNVSPNTNSEKVFSICVMLIGSLMYASIFGNVSAIIQRLYSGTARYHTQMLRVKEFIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGFPECLQADICLHLHRALLQHCPAFSGAGKGCLRALAVKFKTTHAPPGDTLVHLGDVLSTLYFISRGSIEILRDDVVVAILGKNDIFGEPVSLHAQPGKSSADVRALTYCDLHKIQRADLLEVLDMYPAFAESFWSKLEVTFNLRDAAGGLHSSPRQAPGSQDHQGFFLSDNQSGSPHELGPQFPSKGYSLLGPGSQNSMGAGPCAPGHPDAAPPLSISDASGLWPELLQEMPPRHSPQSPQEDPDCWPLKLGSRLEQLQAQMNRLESRVSSDLSRILQLLQKPMPQGHASYILEAPASNDLALVPIASETTSPGPRLPQGFLPPAQTPSYGDLDDCSPKHRNSSPRMPHLAVATDKTLAPSSEQEQPEGLWPPLASPLHPLEVQGLICGPCFSSLPEHLGSVPKQLDFQRHGSDPGFAGSWGH

Function of KCNH6 Membrane Protein

KCNH6 is a member of pore-forming (alpha) subunit. It plays a vital role in many biological processes, include regulating neurotransmitter release, heart rate, and insulin secretion. Previous studies have shown that it has high expression in several tissues, such as kidney, small intestine, and prostate, which suggests it could be involved in tissue regulation and progression. In addition, studies have confirmed that KCNH6 is expressed throughout the brain of rats, including the olfactory bulb, cerebral cortex, hippocampus, hypothalamus, and cerebellum.

Fig.1 Sequence and structure of the C-terminal region of ERG channels. (Gardner, 2015)

Application of KCNH6 Membrane Protein in Literature

Niday Z., et al. Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox. Neuroscientist. 2018, 24(4):368-380. PubMed ID: 29542386

This article analyses the expression levels of these epilepsy-related genes (KCNA2, KCNB1, KCND2, KCNH1, KCNH6, KCNJ10, KCNMA1, KCNQ2, KCNQ3, and KCNT1) and identifies the potential mechanisms of the development of seizures and epilepsy in patients. These results show that these genes may be targets for clinical therapy.
Hassinen M., et al. Molecular basis and drug sensitivity of the delayed rectifier (IKr) in the fish heart. Comp Biochem Physiol C Toxicol Pharmacol. 2015, 176-177: 44-51. PubMed ID: 26215639

This article reports that the marked difference between fish and mammalian Erg1/2, and the data reveals that the Erg1/2 model in different species may affect the function of drug sensitivity.
Fufa T.D., et al. The Tax oncogene enhances ELL incorporation into p300 and P-TEFb containing protein complexes to activate transcription. Biochem Biophys Res Commun. 2015, 465(1): 5-11. PubMed ID: 26188510

Authors in this group focus on the role of lysine-rich leukemia protein during the HTLV-1 Tax oncogene-induced transactivation. These results demonstrate that a novel ELL-dependent transactivation induced by immediate early genes Tax.
Huang Q., et al. Evolutionary analysis of voltage-gated potassium channels by Bayes method. J Mol Neurosci. 2014, 53(1): 41-9. PubMed ID: 24318840

This article examines the expression levels of Voltage-gated potassium channels (VGPCs) related family genes in different species such as human, rat, mice. The data illustrate that KCNH subfamily plays an important role in this family.
Proverbio M.C., et al. Whole genome SNP genotyping and exome sequencing reveal novel genetic variants and putative causative genes in congenital hyperinsulinism. PLoS One. 2013, 8(7): e68740. PubMed ID: 23869231

This article evaluates the expression of genes related with insulin secretion such as transmembrane proteins genes (CACNA1A, KCNH6, KCNJ10, NOTCH2, RYR3, SCN8A, TRPV3, TRPC5), cytosolic and mitochondrial enzymes genes. These results suggest that mutations in those genes may contribute to the development of congenital hyperinsulinism of infancy.

KCNH6 Preparation Options

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Reference

Gardner A, et al. (2015). C-Linker Accounts for Differential Sensitivity of ERG1 and ERG2 K+ Channels to RPR260243-Induced Slow Deactivation. Mol Pharmacol. 88(1): 19-28.

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