KCNQ1 Membrane Protein Introduction

Introduction of KCNQ1

KCNQ1 is encoded by the KCNQ1 gene which is located on the chromosome 11p15.5 in humans. The molecular mass of KCNQ1 is about 70 kDa. It belongs to the potassium channel family, the members of which are wildly expressed in ion channels. KCNQ1 is wildly expressed in the pancreas, prostate, kidney, peripheral blood leukocytes and small intestine. Besides, KCNQ1 can be phosphorylated at Ser-27 by PKA, and ubiquitinated by NEDD4L, both posttranslational modifications can influence the biological functions of KCNQ1 in vivo.

Function of KCNQ1 Membrane Protein

KCNQ1 is a potassium channel which plays a crucial role in maintaining ion balance and modulating current kinetics in humans. KCNQ1 can induce a voltage-dependent potassium-selective outward current. KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (IKs) channels. It takes part in cardiac repolarization when the beta-adrenergic receptor is stimulated. KCNQ1 current can be heavily inhibited by muscarinic agonist oxotremorine-M. Beyond that, KCNQ1 also plays important roles in delayed rectifier potassium channel activity, protein kinase A catalytic subunit binding, protein phosphatase 1 binding, sensory perception of sound and scaffold protein binding and many other biological functions. Besides, the mutations that influence the expression of KCNQ1 can cause long QT syndrome 1 (LQT1), a heart disorder. And the mutations of KCNQ1 are also associated with atrial fibrillation, familial 3 (ATFB3), and diabetes mellitus, non-insulin-dependent (NIDDM), a multifactorial disorder of glucose homeostasis. At the same time, a genome-wide association study suggests that single nucleotide polymorphisms (SNPs) in KCNQ1 are associated with type 2 diabetes.

Fig.1 KCNQ1 structure. (Sun, 2017)

Application of KCNQ1 Membrane Protein in Literature

1. Paquin A., et al. Even pore-localizing missense variants at highly conserved sites in, KCNQ1-encoded Kv7.1 channels may have wild-type function and not cause type 1 long QT syndrome: Do not rely solely on the genetic test company\"s interpretation. HeartRhythm Case Reports. 2017, S2214027117300751. PubMed ID: 29876285
   
   

   This article talks about a hot topic which is about genetic test company and the risk of illness. Authors indicate that mutations of KCNQ1 are associated with type 1 long QT syndrome, which is a fact has been proved. But even pore-localizing missense variants at highly conserved sites in KCNQ1 will not change the wild type function.

2. Asahara S.I., et al. Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β-cell mass by epigenetic modification of Cdkn1c. Proceedings of the National Academy of Sciences. 2015, 112(27). PubMed ID: 26100882
   
   

   It has been reported that mutations of KCNQ1 are a susceptibility factor for type 2 diabetes. This article reports a mutation in KCNQ1, which can reduce pancreatic β-cell mass in mice. And authors reveal that genomic imprinting may be a determinant of the onset of diabetes mellitus.

3. Zhang H., et al. Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus. Journal of Cell Biology. 2014, 204(1):61-75. PubMed ID: 24395636
   
   

   Recently, research about all kinds of RNA has become a hot topic. Authors in this article find that Kcnq1ot1, a long noncoding ribonucleic acid (lnc RNA), takes part in the regulation of genes within the KCNQ1 imprinting domain.

4. Peng D. Purification and Structural Study of the Voltage-Sensor Domain of the Human KCNQ1 Potassium Ion Channel. Biochemistry. 2014, 53(12):2032-2042. PubMed ID: 24606221
   
   

   KCNQ1 is an important ion channel subunit in human. Authors in this article describe the overexpression, purification and preliminary structural characterization of the voltage-sensor domain (VSD) of human KCNQ1. The study provides a structural insight for KCNQ1.

5. Barrosoria R., et al. KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions. Proc Natl Acad Sci U S A. 2017, 114(35): E7367. PubMed ID: 28808020
   
   

   As we all know, KCNE β-subunits can modulate the properties of KCNQ1, and KCNE1 and KCNE3, which are relative to KCNQ1 channel gating. Authors in this article reveal the difference between the mechanisms that KCNE1 and KCNE3 modify the KCNQ1 channel gating.

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Reference

1. Sun J and Mackinnon R. (2017). Cryo-EM structure of a kcnq1/cam complex reveals insights into congenital long qt syndrome. Cell. 169(6): 1042-1050.

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