KCNK16
Domain
The pore-forming domains 1 and 2 assemble to form a single pore in which M2 and M4 transmembrane helices line the central cavity and M1 and M3 face the lipid bilayer. The transmembrane helices are bridged by the selectivity filters 1 and 2 carrying a signature sequence TxTTxGYGD that coordinate the permeant ions. Up to four ions can simultaneously occupy the selectivity filter and at least two elementary charges must translocate across the filter to convert it into the open conformation.
Function
K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate (PubMed:11263999, PubMed:12724142, PubMed:14985088, PubMed:26919430, PubMed:28928238, PubMed:34032641, PubMed:36063992). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:36063992). In pancreatic islets, conducts K(+) countercurrents for Ca(2+) release from the endoplasmic reticulum (ER) and regulates the frequency and duration of cytosolic Ca(2+) oscillations coupled to secretion of pancreatic hormones (PubMed:26239056, PubMed:28928238, PubMed:29402588, PubMed:34032641). In pancreatic beta cells, drives ER Ca(2+) efflux, which in turn activates Ca(2+)-dependent plasma membrane K(+) slow currents and cytosolic Ca(2+) influx, overall contributing to synchronous cytosolic Ca(2+) oscillations. Limits glucose-induced cytosolic Ca(2+) oscillations coupled to second-phase INS secretion (PubMed:26239056, PubMed:28928238, PubMed:34032641). Contributes to beta cell adaptation to acute inflammation by maintaining normal cytosolic Ca(2+) levels and INS secretion (By similarity). May regulate beta cell mitochondrial Ca(2+) levels either indirectly via ER Ca(2+) efflux or directly by hyperpolarizing the mitochondrial membrane potential. Limits mitochondrial Ca(2+) oscillations and ATP production involved in glucose homeostasis upon metabolic stress (By similarity). In pancreatic delta cells, limits Ca(2+)-induced Ca(2+)-release involved in somatostatin secretion and modulates islet paracrine signaling involved in glucagon secretion (PubMed:29402588). Permeable to other monovalent cations such as Rb(+) and Cs(+) (By similarity) (PubMed:26919430).
Sequence Similarities
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
Tissue Specificity
Highly expressed in pancreas, in both endocrine (alpha, beta, gamma, delta, and epsilon) and exocrine (acinar and ductal) cells. Expressed in pacreatic beta-cells (at protein level). Expressed in pacreatic delta-cells (at protein level). Not detectable in the other tissues tested.
Cellular localization
- Isoform a
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
- Isoform b
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Mitochondrion inner membrane
- Multi-pass membrane protein
Alternative names
TALK1, KCNK16, Potassium channel subfamily K member 16, 2P domain potassium channel Talk-1, TWIK-related alkaline pH-activated K(+) channel 1, TALK-1