KCNK15 Membrane Protein Introduction

Introduction of KCNK15

Potassium channel subfamily K member 15 (KCNK15), also known as acid-sensitive potassium channel protein TASK-5, K_2P15.1 or KT3.3, is encoded by gene KCNK15, showing sequence homology with TASK-1 (KCNK3) and TASK-3 (KCNK9). KCNK15 belongs to the two-pore-domain (K2P) family of K⁺-selective channels, a category of the eukaryotic mechanosensitive ion channel. Similar to KCNK6, KCNK7, and THIK-2, KCNK15 cannot produce a functional plasma membrane K⁺ currents by itself, whereas chimeric KCNK15/KCNK9 constructs containing the region between M1 and M3 of KCNK9 can produce K⁺ selective currents. KCNK15 is widely expressed in pancreas, liver, kidney, lung, ovary, testis and heart. The architecture of KCNK15 is characterized by four transmembrane helixes (M1-M4), an extracellular cap domain and a pseudo-tetrameric architecture around the central selectivity filter. KCNK15 is mapped to chromosomal region 20q12-20q13.

Function of KCNK15 Membrane Protein

KCNK15 is classified into the TWIK-related acid-sensitive K⁺ (TASK) channels, which not only primarily determine the membrane potential, input resistance and excitability of neurons, but may also contribute to the production of cerebrospinal fluid in the brain. As a member of TASKs subfamily, KCNK15 also plays important roles in setting the resting potential of mammalian neurons and the regulation of neuronal activity. With high sensibility to physical and chemical stimuli, TASKs are regulated via G-protein-coupled receptors and phosphorylation, and they are believed to be novel targets for extracellular protons and volatile anesthetics such as halothane. It is documented that in conjunction with auxiliary proteins, KCNK15 K⁺ channels may play an important role in the transmission of temporal information in the auditory system. Down-expression of KCNK15 is significantly associated with triple negative breast cancer subtype. It has been reported that the long non-coding RNA (lncRNA) KCNK15-AS1 is downregulated in pancreatic cancer tissues, and alkylation repair homolog protein 5 (ALKBH5) may inhibit pancreatic cancer motility by decreasing lncRNA KCNK15-AS1 methylation.

Fig.1 Interplay between TASK channel and c-Src in human pulmonary artery smooth muscle cells. (Nagaraj, 2012)

Application of KCNK15 Membrane Protein in Literature

1. He Y., et al. ALKBH5 Inhibits Pancreatic Cancer Motility by Decreasing Long Non-Coding RNA KCNK15-AS1 Methylation. Cellular Physiology and Biochemistry. 2018, 48(2): 838-846. PubMed ID: 30032148
   
   

   In this article, the authors evaluated the differential expression of cancer cells and matched normal cells to identify the lncRNA KCNK15-AS1 was downregulated in pancreatic cancer tissues. Alkylation repair homolog protein 5 (ALKBH5) inhibited pancreatic cancer motility by decreasing lncRNA KCNK15-AS1 methylation.

2. Kim D and Gnatenco C. TASK-5, a new member of the tandem-pore K⁺ channel family. Biochemical and biophysical research communications. 2001, 284(4): 923-930. PubMed ID: 11409881
   
   

   The authors cloned TASK-5 and studied its tissue expression and functional properties. They showed that TASK-5 was expressed primarily in the adrenal gland and pancreas and there was one single nucleotide polymorphism (SNP) in amino acid position 95 that normally formed part of the K⁺ channel selectivity filter.

3. Ashmole I., et al. TASK-5, a novel member of the tandem pore K⁺ channel family. Pflügers Archiv. 2001, 442(6): 828-833. PubMed ID: 11680614
   
   

   This article firstly cloned a novel member of the tandem pore K⁺ channel family from human brain cDNA and named the channel TASK-5. They also revealed that TASK-5 did not form heteromers with TASK-1, nonetheless, it may require some other partner subunit to form functional channels in the plasma membrane.

4. Karschin C., et al. Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K⁺ channel subunit, TASK-5, associated with the central auditory nervous system. Molecular and Cellular Neuroscience. 2001, 18(6): 632-648. PubMed ID: 11749039
   
   

   The authors demonstrated that TASK-5 was mainly expressed in olfactory bulb mitral cells and Purkinje cells, predominantly associated with the central auditory pathway. By conjunction with auxiliary proteins, TASK-5 may contribute to the transmission of temporal information in the auditory system.

5. Nagaraj C., et al. Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. European Respiratory Journal. 2012, 41(1):85-95. PubMed ID: 22523355
   
   

   The authors identified SrcTK was a crucial factor controlling potassium channels, such as TASK-1 channel, so it could act as a cofactor for setting a negative resting membrane potential and a low resting pulmonary vascular tone in hPASMCs.

KCNK15 Preparation Options

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Reference

1. Nagaraj C, et al. (2012). Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. European Respiratory Journal. 41(1):85-95.

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