KCNK5 Membrane Protein Introduction

Introduction of KCNK5

KCNK5, the full name is potassium channel subfamily K member 5, also known as acid-sensitive potassium channel protein TASK-2, TWIK-related acid-sensitive K(+) channel 2. KCNK5 is a pH-sensitive potassium channel that is expressed in many different tissues including the liver, pancreas, small intestine, and kidney. The KCNK5 current is activated by alkaline intra- or extracellular pH and is inhibited by the acidic pH on either side of the membrane.

Basic Information of KCNK5
Protein Name	Potassium channel subfamily K member 5
Gene Name	KCNK5
Aliases	Acid-sensitive potassium channel protein TASK-2, TWIK-related acid-sensitive K(+) channel 2
Organism	Homo sapiens (Human)
UniProt ID	O95279
Transmembrane Times	4
Length (aa)	499
Sequence	MVDRGPLLTSAIIFYLAIGAAIFEVLEEPHWKEAKKNYYTQKLHLLKEFPCLGQEGLDKILEVVSDAAGQGVAITGNQTFNNWNWPNAMIFAATVITTIGYGNVAPKTPAGRLFCVFYGLFGVPLCLTWISALGKFFGGRAKRLGQFLTKRGVSLRKAQITCTVIFIVWGVLVHLVIPPFVFMVTEGWNYIEGLYYSFITISTIGFGDFVAGVNPSANYHALYRYFVELWIYLGLAWLSLFVNWKVSMFVEVHKAIKKRRRRRKESFESSPHSRKALQVKGSTASKDVNIFSFLSKKEETYNDLIKQIGKKAMKTSGGGETGPGPGLGPQGGGLPALPPSLVPLVVYSKNRVPTLEEVSQTLRSKGHVSRSPDEEAVARAPEDSSPAPEVFMNQLDRISEECEPWDAQDYHPLIFQDASITFVNTEAGLSDEETSKSSLEDNLAGEESPQQGAEAKAPLNMGEFPSSSESTFTSTESELSVPYEQLMNEYNKANSPKGT

Function of KCNK5 Membrane Protein

Only a portion (about 25%) of KCNK5 is open at physiological pH. It is controlled by internal and external pH and has sufficient room for alkalizing activation. The intracellular pH-gated properties are shared by KCNK5 homologs of TALK. The KCNK5 channel is involved in renal bicarbonate reabsorption as well as signaling processes in central CO₂ and O₂-sensitive neurons, which helps control breathing. The function of KCNK5 has been proposed to regulate chondrocyte membrane potential and metabolic activity, to maintain lymphocyte population through apoptosis, to control cell excitability in neonatal dorsal root ganglion neurons, and to regulate excitability in intestinal smooth muscle cells. Interestingly, KCNK5 may play a central role in the regulation of proliferation in breast estrogen-dependent cancer cells, making it a putative target in cancer therapy.

Fig.1 A molecular model for the KCNK5 pore based on the structure of TRAAK. The blue region mimics the location of the extracellular ion pathway (EIP) and R224 pHo sensor of the KCNK5 channel. (Cid, 2013)

Application of KCNK5 Membrane Protein in Literature

Kirkegaard S.S., et al. The Volume Activated Potassium Channel KCNK5 is Up-Regulated in Activated Human T Cells, but Volume Regulation is Impaired. Cell Physiol Biochem. 2016, 38(3):883-92. PubMed ID: 26909737

The results showed that up-regulated KCNK5 in activated human T cells did not regulate the volume due to decreased Cl-permeability, suggesting that up-regulation of KCNK5 may play a role in hyperpolarization of cell membranes, leading to the increased Ca²⁺ influx and T cell proliferation.
Schulte-Mecklenbeck A., et al. The two-pore domain K2P channel TASK2 drives human NK-cell proliferation and cytolytic function. Eur J Immunol. 2015, 45(9):2602-14. PubMed ID: 26140335

Potassium channel TASK2 could drive human NK-cell proliferation and cytolytic function.
Toncheva D., et al. NGS nominated CELA1, HSPG2, and KCNK5 as candidate genes for predisposition to Balkan endemic nephropathy. Biomed Res Int. 2014, 920723. PubMed ID: 24949484

Mutant genes (CELA1, HSPG2, and KCNK5) in patients with endemic nephropathy in Balkans were involved in the basement membrane/extracellular matrix and vascular tone, which were closely related to the angiogenic process.
Lenzini L., et al. Lower expression of the TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene is a hallmark of aldosterone-producing adenoma causing human primary aldosteronism. J Clin Endocrinol Metab. 2014, 99(4):E674-82. PubMed ID: 24285684

Low expression of the TASK-2 channel represented a marker for aldosterone-producing adenomas that caused aldosteronism and was associated with a higher expression of hsa-miR-23 and hsa-miR-34.
Alvarez-Baron C.P., et al. The two-pore domain potassium channel KCNK5: induction by estrogen receptor alpha and role in proliferation of breast cancer cells. Mol Endocrinol. 2011, 25(8):1326-36. PubMed ID: 21680658

17β-estradiol induced expression of KCNK5 in breast cancer cells by ERα(+) was verified, and this channel played a role in regulating proliferation in these cell lines.

KCNK5 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms or other protein forms in the same family. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-KCNK5 antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

Cid L P, et al. (2013). TASK-2: a K2P K(+) channel with complex regulation and diverse physiological functions. Front Physiol. 4:198.

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