| KCNK13 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | KCNK13 , K2p13.1, THIK-1, THIK1, potassium two pore domain channel subfamily K member 13 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607367; MGI: 2384976; HomoloGene: 69351; GeneCards: KCNK13; OMA:KCNK13 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Potassium channel, subfamily K, member 13 (KCNK13), also known as K2P13.1 or THIK-1, is a protein that in humans is encoded by the KCNK13 gene. It is a potassium channel containing two pore-forming P domains. [5] [6]
K2P13.1 was first discovered in 2000 from a rat cDNA library, along with the closely related protein K2P12.1 [8] The two channels were named tandem pore domain halothane-inhibited K+ channel 1 and 2 (THIK-1 and THIK-2) because the anesthetic halothane inhibited the potassium current. THIK-1 was also shown to be activated by arachidonic acid and displayed mild voltage dependence, with moderate outward rectification at low external K+ and weak inward rectification with nearly symmetrical K+ concentrations. [8] [9] Later research showed that THIK-1 can be activated by G-protein-coupled receptor pathways [10] and by polyanionic lipids such as PIP2 and oleoyl-CoA. [11]
In humans, THIK-1 expression is almost exclusively restricted to microglia, where it functions as the main potassium channel and is responsible for maintaining their resting membrane potential through tonic background potassium conductance [12] . THIK-1 activity can regulate microglial ramification, surveillance, NLRP3 inflammasome activation, and subsequent release of pro-inflammatory cytokine interleukin-1β (IL-1β) [13] [14] [15] . It also plays a role in cell shrinkage during apoptosis via caspase-8 cleavage. [16]
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells.
NLR family pyrin domain containing 3 (NLRP3), is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1.
Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.
Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene.
Potassium inwardly-rectifying channel, subfamily J, member 8, also known as KCNJ8, is a human gene encoding the Kir6.1 protein. A mutation in KCNJ8 has been associated with cardiac arrest in the early repolarization syndrome.
Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the KCNK2 gene.
Potassium channel subfamily K member 9 is a protein that in humans is encoded by the KCNK9 gene.
Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene. KCNK4 protein channels are also called TRAAK channels.
NLR family CARD domain-containing protein 4 is a protein that in humans is encoded by the NLRC4 gene.
Potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13) is a human gene encoding the Kir7.1 protein.
Potassium channel subfamily K member 15 is a protein that in humans is encoded by the KCNK15 gene.
Potassium channel subfamily K member 17 is a protein that in humans is encoded by the KCNK17 gene.
The nucleotide-binding oligomerization domain-like receptors, or NOD-like receptors (NLRs), are intracellular sensors of pathogen-associated molecular patterns (PAMPs) that enter the cell via phagocytosis or pores, and damage-associated molecular patterns (DAMPs) that are associated with cell stress. They are types of pattern recognition receptors (PRRs), and play key roles in the regulation of innate immune response. NLRs can cooperate with toll-like receptors (TLRs) and regulate inflammatory and apoptotic response.
Potassium channel, subfamily K, member 10, also known as KCNK10 is a human gene. The protein encoded by this gene, K2P10.1, is a potassium channel containing two pore-forming P domains.
Potassium channel, subfamily K, member 12, also known as KCNK12 is a human gene. The protein encoded by this gene, K2P12.1, is a potassium channel containing two pore-forming P domains.
Potassium channel subfamily K member 16 is a protein that in humans is encoded by the KCNK16 gene. The protein encoded by this gene, K2P16.1, is a potassium channel containing two pore-forming P domains.
Inflammasomes are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death. They are formed as a result of specific cytosolic pattern recognition receptors (PRRs) sensing microbe-derived pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) from the host cell, or homeostatic disruptions. Activation and assembly of the inflammasome promotes the activation of caspase-1, which then proteolytically cleaves pro-inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as the pore-forming molecule gasdermin D (GSDMD). The N-terminal GSDMD fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, which is responsible for the release of mature cytokines. Additionally, inflammasomes can act as integral components of larger cell death-inducing complexes called PANoptosomes, which drive another distinct form of pro-inflammatory cell death called PANoptosis.
NOD-like receptor family pyrin domain containing 11 is a protein that in humans is encoded by the NLRP11 gene located on the long arm of human chromosome 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of CATERPILLER. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6
Gasdermin D is a protein that in humans is encoded by the GSDMD gene on chromosome 8. It belongs to the gasdermin family which is conserved among vertebrates and comprises six members in humans, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5) and DFNB59 (Pejvakin). Members of the gasdermin family are expressed in a variety of cell types including epithelial cells and immune cells. GSDMA, GSDMB, GSDMC, GSDMD and GSDME have been suggested to act as tumour suppressors.
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