Close

KCNK1 Membrane Protein Introduction

Introduction of KCNK1

Potassium channel subfamily K member 1 (KCNK1), also known as inward rectifying potassium channel protein TWIK1, is encoded by the gene KCNK1. Originally cloned from human brain in 1996, KCNK1 is classified into the family of two-pore-domain potassium (K2P) channels, sharing the same overall architecture with four membrane-spanning segments (M1-M4), two pore domains (P1 and P2), involved in the formation of the selectivity filter, and a large extracellular M1P1 loop. Usually, two KCNK1 monomers containing four TMs assemble to form the functional homodimers ion conduction pathway. Beyond the brain, TWIK1 is also expressed at significant levels in other tissues including heart, kidney, pancreas, lung, and placenta. Significantly, TWIK1 is mainly localized in the pericentriolar recycling endosomal compartment in polarized and nonpolarized epithelial cells.

Basic Information of KCNK1
Protein Name Potassium channel subfamily K member 1
Gene Name KCNK1
Aliases TWIK1
Organism Homo sapiens (Human)
UniProt ID O00180
Transmembrane Times 4
Length (aa) 336
Sequence MLQSLAGSSCVRLVERHRSAWCFGFLVLGYLLYLVFGAVVFSSVELPYEDLLRQELRKLKRRFLEEHECLSEQQLEQFLGRVLEASNYGVSVLSNASGNWNWDFTSALFFASTVLSTTGYGHTVPLSDGGKAFCIIYSVIGIPFTLLFLTAVVQRITVHVTRRPVLYFHIRWGFSKQVVAIVHAVLLGFVTVSCFFFIPAAVFSVLEDDWNFLESFYFCFISLSTIGLGDYVPGEGYNQKFRELYKIGITCYLLLGLIAMLVVLETFCELHELKKFRKMFYVKKDKDEDQVHIIEHDQLSFSSITDQAAGMKEDQKQNEPFVATQSSACVDGPANH

Function of KCNK1 Membrane Protein

The KCNK1-formed two P-domain K+ (K2P) channels can produce time- and voltage-independent currents opposing membrane depolarization and cell excitability, which is distinctive from many other K+ channels. It is documented that KCNK1 activation is modulated by a diverse array of chemical and physical stimulus including pH, temperature, unsaturated fatty acids, and membrane stretch, etc. As an important component of K2P channels, KCNK1 is proposed to participate in widely physiological processes, such as apoptosis, adrenal gland development, and primary hyperaldosteronism, neuronal excitability and altered motor performance, central O2 chemoreception and breathing control, pain signaling, etc. Strong evidence showed that KCNK1 is functional and contributes to membrane trafficking/expression of transport molecules in the kidney, with impaired regulation of phosphate transport in the proximal tubule and of water transport in the medullary collecting duct in KCNK1 deficient mice. Moreover, KCNK1 is suggested to address to the cell surface when expressed in Xenopus oocytes and combines with a small ubiquitin modifier (SUMO) peptide to its lysine 274 (K274) site, which is responsible for a block of channel activity.

TWIK1 sequence and topological organization. Fig.1 TWIK1 sequence and topological organization. (Chatelain, 2012)

Application of KCNK1 Membrane Protein in Literature

  1. Chatelain F.C., et al. TWIK1, a unique background channel with variable ion selectivity. Proceedings of the National Academy of Sciences. 2012, 109(14): 5499-5504. PubMed ID: 28723241

    In this article, the authors demonstrated that the K+ selectivity of TWIK1 was modulated by extracellular pH, while at the acidic pH condition found in endosomes, it became permeable to Na+. TWIK1−/− pancreatic β cells are more polarized compared with control, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.

  2. Decressac S., et al. ARF6-dependent interaction of the TWIK1 K+ channel with EFA6, a GDP/GTP exchange factor for ARF6. EMBO reports. 2004, 5(12): 1171-1175. PubMed ID: 28392258

    This article identified TWIK1 could interact with EFA6, an exchange factor for the small G protein ADP-ribosylation factor 6 (ARF6) and the association only occurred after the binding with ARF6. ARF6/EFA6/TWIK1 association played probably an important role in channel internalization and recycling.

  3. Feliciangeli S., et al. Does sumoylation control K2P1/TWIK1 background K+ channels? Cell. 2007, 130(3): 563-569. PubMed ID: 27241700

    This article demonstrated that only the mutation K274E in TWIK1, not K274R, was responsible for an increase of K2P1 current density, suggesting a charge effect of K274E. K274E mutation was the putative sumoylation site, which gave rise to robust current expression in transfected COS-7 cells.

  4. Blin S., et al. Tandem pore domain halothane-inhibited K+ channel subunits THIK1 and THIK2 assemble and form active channels. Journal of Biological Chemistry. 2014, M114: 600437. PubMed ID: 25500157

    The authors reported that THIK1 could assemble with THIK2 to form active channels via the dominant negative control of pore-mutated subunits, in situ proximity ligation assay, FRET, and electrophysiology of covalent THIK1/THIK2 dimers.

  5. Pollema-Mays S.L., et al. Expression of background potassium channels in rat DRG is cell-specific and down-regulated in a neuropathic pain model. Molecular and Cellular Neuroscience. 2013, 57: 1-9. PubMed ID: 27609046

    The authors confirmed that TWIK1 could be detected in large and medium-size neurons, independent of TRPV1 or IB4 expression, suggesting involvement of TWIK1 in the maintenance of the pain condition.

KCNK1 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-KCNK1 antibody development services.


Over years, Creative Biolabs has successfully generated many functional membrane proteins for our customers. We are happy to tailor one-stop, custom-oriented service packages regarding a variety of membrane protein targets. Please feel free to contact us for more information.

Reference

  1. Chatelain F C, et al. (2012). TWIK1, a unique background channel with variable ion selectivity. Proceedings of the National Academy of Sciences. 109(14): 5499-5504.

Online Inquiry

Verification code
Click image to refresh the verification code.

CONTACT US

45-1 Ramsey Road, Shirley, NY 11967, USA
Call us at:
USA: 1-631-381-2994
Europe: 44-207-097-1828
Fax: 1-631-207-8356
Email:
Our customer service representatives are available 24 hours a day, 7 days a week. Contact Us