KCNK16 Membrane Protein Introduction

Introduction of KCNK16

KCNK16, the full name is potassium channel subfamily K member 16, also known as 2P domain potassium channel Talk-1, TWIK-related alkaline pH-activated K(+) channel 1 (TALK-1). KCNK16, which codes for the TALK-1 channel, is the most abundant K⁺ channel transcript found in human pancreatic islets β-cells. The secondary structure of TALK-1 contains four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. There are four human TALK-1 transcript variants, including two that form functional K⁺ channels: TALK-1a (transcript variant 2 (T2)) and TALK1-b (transcript variant 3 (T3)). Similar to several other K2P channels, TALK-1 is sensitive to pH, and it increases activity under alkaline conditions, while decreases activity under acidic conditions.

Basic Information of KCNK16
Protein Name	Potassium channel subfamily K member 16
Gene Name	KCNK16
Aliases	2P domain potassium channel Talk-1, TWIK-related alkaline pH-activated K(+) channel 1 (TALK-1)
Organism	Homo sapiens (Human)
UniProt ID	Q96T55
Transmembrane Times	4
Length (aa)	309
Sequence	MPSAGLCSCWGGRVLPLLLAYVCYLLLGATIFQLLERQAEAQSRDQFQLEKLRFLENYTCLDQWAMEQFVQVIMEAWVKGVNPKGNSTNPSNWDFGSSFFFAGTVVTTIGYGNLAPSTEAGQVFCVFYALLGIPLNVIFLNHLGTGLRAHLAAIERWEDRPRRSQVLQVLGLALFLTLGTLVILIFPPMVFSHVEGWSFSEGFYFAFITLSTIGFGDYVVGTDPSKHYISVYRSLAAIWILLGLAWLALILPLGPLLLHRCCQLWLLSLRQGCGAKAAPGRRPRRGSTAARGVQVTPQDFPISKKGLGS

Function of KCNK16 Membrane Protein

The TALK-1 K⁺ channel regulates beta cell electrical excitability by polarizing beta cell membrane potential (Vm). Islet beta cells from TALK-1 knockout (KO) mice showed increased Vm depolarization, increased Ca²⁺ influx and elevated second phase glucose-stimulated insulin secretion (GSIS). In addition, non-synonymous polymorphisms in TALK-1 (rs1535500) resulted in the replacement of 277 alanine (A) with glutamate (E), which is associated with an increased risk of type 2 diabetes. This polymorphism leads to a gain-of-function (GOF) of TALK-1 channel that increases its open probability, predicts its hyperpolarized beta cell Vm and decreases Ca²⁺ influx and insulin secretion.

Dendrogram of 2P domain K<sup>+</sup> channels. Fig.1 Dendrogram of 2P domain K⁺ channels.

Application of KCNK16 Membrane Protein in Literature

Vierra N.C., et al. TALK-1 reduces delta-cell endoplasmic reticulum and cytoplasmic calcium levels limiting somatostatin secretion. Mol Metab. 2018, 9:84-97. PubMed ID: 29402588

These data indicated that TALK-1 reduced cytosolic Ca²⁺ elevations of δ-cell and somatostatin released by limiting δ-cell Ca²⁺-induced Ca²⁺ release (CICR), modulating the intraislet paracrine signaling mechanisms that controlled glucagon secretion.
Vierra N.C., et al. TALK-1 channels control β cell endoplasmic reticulum Ca²⁺ homeostasis. Sci Signal. 2017, 10(497). PubMed ID: 28928238

The data herein established TALK-1 channel as a key regulator of ER Ca(2+) in β-cells, and suggested that TALK-1 may be a therapeutic target for reducing ER Ca(2+) treatment defected in β-cells during the pathogenesis of diabetes.
Dickerson M.T., et al. Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells. PLoS One. 2017, 12(4):e0175069. PubMed ID: 28403169

The TALK-1/iOPN complex caused Vm hyperpolarization and reduced β-cell glucose-stimulated Ca²⁺ influx, which is predicted to inhibit glucose-stimulated insulin secretion (GSIS).
Vierra N.C., et al. Type 2 Diabetes-Associated K⁺ Channel TALK-1 Modulates β-Cell Electrical Excitability, Second-Phase Insulin Secretion, and Glucose Homeostasis. Diabetes. 2015, 64(11):3818-28. PubMed ID: 26239056

These findings revealed the TALK-1 channel as an important regulator of second-stage insulin secretion and suggested a clinically relevant mechanism for rs1535500 that increased the risk of type 2 diabetes by limiting glucose-stimulated insulin secretion.
Han J., et al. Functional properties of four splice variants of a human pancreatic tandem-pore K⁺ channel, TALK-1. Am J Physiol Cell Physiol. 2003, 285(3):C529-38. PubMed ID: 12724142

It had been discovered herein that at least two functional TALK-1 variants were present and could be used as background K⁺ currents in certain cells of the human pancreas.

KCNK16 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-KCNK16 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

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.

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