TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.2.1.1









ATP-activated inward rectifier K+ channel, IRK1 (also called ROMK or KIR1.1) (regulated by Sur1, allowing ATP sensitivity; also activated by phosphatidylinositol 4,5-bisphosphate (PIP) with affinity to PIP controlled by protein kinase A phosphorylation (which increases affinity for PIP)) and protein kinase C phosphorylation (which decreases affinity for PIP (Zeng et al., 2003). Alternariol (AOH), the most important mycotoxin produced by Alternaria species, which are the most common mycoflora infecting small grain cereals worldwide, causes loss of cell viability by inducing apoptosis. AOH-induced apoptosis through a mitochondria-dependent pathway is characterized by p53 activation, an opening of the mitochondrial permeability transition pore (PTP), loss of mitochondrial transmembrane potential (ΔΨm), a downstream generation of O2- and caspase 9 and 3 activation (Bensassi et al., 2012). Pharmacological inhibition of renal ROMK causes diuresis and natriuresis in the absence of kaliuresis (Garcia et al. 2013).

Eukaryota
Metazoa
IRK1 of Homo sapiens (P48048)
*1.A.2.1.2









G-protein enhanced inward rectifier K channel 2, IRK2 (Kir2.1) (Andersen-Tawil Syndrome (ATS-1) protein; the V302M mutation causing the syndrome, alters the G-loop cytoplasmic K conduction pathway) (Bendahhou et al., 2003; Ma et al., 2007). (Blocked by chloroquine which binds in the cytoplasmic pore domain (Rodriguez-Menchaca et al., 2008)). Forms heteromultimers with Kir3.1 and Kir3.4 (Ishihara et al., 2009). A C-terminal domain is critical for the sensitivity of Kir2.1 to cholesterol (Epshtein et al., 2009). Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification (Caballero et al., 2010).  The inhibitory cholesterol binding site has been identified (Fürst et al. 2014).  Polyamines and Mg2+ block ion flux synergistically (Huang and Kuo 2016).

Eukaryota
Metazoa
IRK2 of Homo sapiens (P63252)
*1.A.2.1.3









G-protein activated IRK5 channel. The p75 neurotrophin receptor mediates cell death by activating GIRK channels through phosphatidylinositol 4,5-bisphosphate (Coulson et al., 2008). Cholesterol up-regulates neuronal GIRK channel activity (Bukiya et al. 2017).

Eukaryota
Metazoa
IRK5 of Homo sapiens (P48544)
*1.A.2.1.4









Hepatocyte basolateral inwardly rectifying K+ channel, Kir4.2, involved in bile secretion (Hill et al., 2002)
Eukaryota
Metazoa
Kir4.2 of Rattus norvegicus (Q91ZF1)
*1.A.2.1.5









Cranial nerve inward rectifying K+ channel, Kir2.4 (IRK4) (Töpert et al., 1998)

Eukaryota
Metazoa
Kir2.4 of Rattus norvegicus (O70596)
*1.A.2.1.6









ATP-sensitive K+ channel, Kir6.3 (Zhang et al., 2005)
Eukaryota
Metazoa
Kir6.3 of Danio rerio (Q5R205)
*1.A.2.1.7









Kidney/pancreas/muscle ATP-senstive, ER/Golgi K+ channel, KATP or ROMK (Kir6.2) (Boim et al., 1995) (three alternatively spliced isoforms are called ROMK1-3). Involved in congenital hyperinsulinism (Lin et al., 2008). Regulated by Ankyrin-B (Li et al., 2010). ATP activates ATP-sensitive potassium channels composed of mutant sulfonylurea receptor 1 (SUR1) and Kir6.2 with diminished PIP2 sensitivity (Pratt and Shyng, 2011). This channel protects the myocardium from hypertrophy induced by pressure-overloading (Alvin et al., 2011). Domain organization studies show which domains in Sur and Kir6.2 interact (Wang et al. 2012).  KATP channels consisting of Kir6.2 and SUR1 couple cell metabolism to membrane excitability and regulate insulin secretion in pancreatic beta cells, and mutations in the former protein can compensate for mutations in the latter (Zhou et al. 2013).  Mutations cause inactivation of channel function by disrupting PIP2-dependent gating (Bushman et al. 2013). Thus, these proteins comprise part of the glucose sensing mechanism (Rufino et al. 2013).  A single point mutation can confer voltage sensitivity (Kurata et al. 2010).  Its involvement in type II diabetes has been reviewed by Bonfanti et al. 2015. KATP channels (Kir6.2/SUR1) in the brain and endocrine pancreas  couple metabolic status to the membrane potential. In beta-cells, increases in cytosolic [ATP/ADP] inhibit KATP channel activity, leading to membrane depolarization and exocytosis of insulin granules. Mutations in ABCC8 (SUR1) or KCNJ11 (Kir6.2) can result in gain or loss of channel activity and cause neonatal diabetes (ND) or congenital hyperinsulinism (CHI), respectively.  Nucleotide binding without hydrolysis switches SUR1 to stimulatory conformations.  Increased affinity for ATP gives rise to ND while decreased affinty gives rise to CHI (Ortiz and Bryan 2015).  Kir6.2 can associate with either SUR1 (TC# 3.A.1.208.4) or SUR2A (TC# 3.A.1.208.23) to form heteroctamers, leading to different locations and consequences (Principalli et al. 2015).

Eukaryota
Metazoa
ROMK of Rattus norvegicus (P70673)
*1.A.2.1.8









The inward rectifier potassium channel 13, Kir 7.1
Eukaryota
Metazoa
Kir 7.1 of Homo sapiens (O60928)
*1.A.2.1.9









The inward-rectifier k+ channel, Kir2.2 at the 3-d structure at 3.1 Å resolution is available (Tao et al., 2009). (70%v identical to Kir2.1 (TC # 1.A.2.1.2)). The structural basis of PIP2 activation of Kir2.2 has been presented (Hansen et al., 2011).

Eukaryota
Metazoa
Kir2.2 of Homo sapiens (Q14500)
*1.A.2.1.10









G-protein-activated inward rectifying K+ channel, Kir3.2 or GIRK (Inanobe et al., 2011; Yokogawa et al. 2011).  Important in regulating heart rate and neuronal excitability.  Activated by binding of the βγ-subunit complex to the cytoplasmic pore gate (Yokogawa et al. 2011). Chen et al. 2017 found that the G-protein-gated inwardly rectifying K+ (GIRK) channel is activated by IVM directly.

Eukaryota
Metazoa
Kir3.2 of Homo sapiens (P48051)
*1.A.2.1.11









Inward rectifying potassium channel 16, Kir5.1. (Potassium channel subfamily J member 16), KCNJ16.  Involved in pH and fluid regulation.  Forms heteromers with Kir4.1/KCNJ10 or Kir2.1/KCNJ2.

Eukaryota
Metazoa
KCNJ16 of Homo sapiens
*1.A.2.1.12









G protein-activated inward rectifying K+ channel 1 (Kir3.1; IRK3; GIRK1). Regulates the heartbeat in humans. Phosphatidylinositol bisphosphate (PIP2) activates by opening the intracelluar G-loop gate (Meng et al., 2012).  Along the ion permeation pathway, three relatively narrow regions (the selectivity filter, the inner helix bundle crossing, and the cytosolic G loop) may serve as gates to control ion permeation (Meng et al. 2016). Cholesterol up-regulates neuronal GIRK channel activity (Bukiya et al. 2017). Changes in the levels of cholesterol and PI(4,5)P2 may act in concert to provide fine-tuning of Kir3 channel function (Bukiya et al. 2017).

Eukaryota
Metazoa
Kir3.1 (IRK3) of Homo sapiens (P48549)
*1.A.2.1.13









ATP-sensitive inward rectifying K  channel 8, Kir6.1. Acts with Sur2B (3.A.1.208.23). Channel activity is inhibited in oxidative stress via S-glutathionylation (Yang et al., 2011). Oxidative sensitivity is dependent on Cys176 (Yang et al., 2011).  These proteins comprise part of the glucose sensing mechanism (Rufino et al. 2013).

Eukaryota
Metazoa
Kir6.1 of Homo sapiens (Q15842)
*1.A.2.1.14









Inward rectifying potassium (K+) (IRK) channel of 426 aas and 2 TMSs, AgaP.

Eukaryota
Metazoa
AgaP of Anopheles gambiae (African malaria mosquito)
*1.A.2.1.15









Kir1 (AgaP) K+ channel of 444 aas and 2 TMSs.

Eukaryota
Metazoa
Kir1 of Anopheles gambiae (African malaria mosquito)
*1.A.2.1.16









Inward rectifying K+ channel, Kir4.1 of 379 aas.  Inhibited by chloroethylclonidine and pentamidine which bind in the channel (Rodríguez-Menchaca et al. 2016; Aréchiga-Figueroa et al. 2017). Also inhibited by chloropuine which inhibits by an open pore blocking mecnanism (Marmolejo-Murillo et al. 2017).

Eukaryota
Metazoa
Kir4.1 of Homo sapiens
*1.A.2.1.17









KCNJ11 or Kir6.2 or KATP of 390 aas; 96% identical to the rat homologue, TC# 1.A.2.1.7. Congenital hyperinsulinism (CHI) is characterized by persistent insulin secretion despite severe hypoglycemia. Mutations in the pancreatic ATP-sensitive K+ (K(ATP)) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease. Many mutations in SUR1 render the channel unable to traffic to the cell surface, thereby reducing channel function. Many studies have shown that for some SUR1 trafficking mutants, the defects could be corrected by treating cells with sulfonylureas or diazoxide (Yan et al. 2007). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium (Tammaro and Ashcroft 2007). Kir6.2 is an ATP-sensitive potassium (KATP) channel coupling cell metabolism to electrical activity by regulating K+ fluxes across the plasma membrane. Channel closure is facilitated by ATP, which binds to the pore-forming subunit (Kir6.2). Conversely, channel opening is potentiated by phosphoinositol bisphosphate (PIP2), which binds to Kir6.2 and reduces channel inhibition by ATP.  The PIP2 binding site has been identified (Haider et al. 2007).  KATP channels are metabolic sensors that couple cell energetics to membrane excitability. In pancreatic beta-cells, channels formed by SUR1 and Kir6.2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas. Martin et al. 2017 used cryo-EM to elucidate the structural basis of channel assembly and gating. The structure, determined in the presence of ATP and the sulfonylurea, glibenclamide, at ~6 Å resolution, revealed a closed Kir6.2 tetrameric core with four peripheral SUR1s, each anchored to a Kir6.2 by its N-terminal transmembrane domain (TMD0). Intricate interactions between TMD0, the loop following TMD0, and Kir6.2 near the proposed PIP2 binding site, and where ATP density is observed, suggest that SUR1 may contribute to ATP and PIP2 binding to enhance Kir6.2 sensitivity to both. The SUR1-ABC core is found in an unusual inward-facing conformation whereby the two nucleotide binding domains are misaligned along a two-fold symmetry axis, revealing a possible mechanism by which glibenclamide inhibits channel activity (Martin et al. 2017).

Eukaryota
Metazoa
Kir6.2 of Homo sapiens
*1.A.2.2.1









Prokaryotic K+-selective Kir channel KirBac1.1 (selectivity: K+ = Rb+ = Cs+ >> Li, Na+ or NMGM) (Enkvetchakul et al., 2004), inward rectifying (Cheng et al., 2009). The inhibitory cholesterol binding site has been identified (Fürst et al. 2014).

Bacteria
Proteobacteria
KirBac1.1 OF Burkholderia pseudomallei (IP7BA; gi33357898)
*1.A.2.2.2









The KirBac3.1 K+ channel (a dimer of dimers with gating visualized by atomic force microscopy, Jaroslawski et al., 2007) (regulated by binding lipids, G-proteins, nucleotides, and ions (H+, Ca2+, and Mg2+)). The 3-D structure is available (1XL6_A).  The inhibitory cholesterol binding site has been identified (Fürst et al. 2014).

Bacteria
Proteobacteria
KirBac3.1 of Magnetospirillum magnetotacticum  (D9N164)
*1.A.2.2.3









ATP-sensitive inward rectifying Kir K channel (Choi et al. 2010).

Bacteria
Proteobacteria
Kir K+ channel of Chromobacterium violaceum
*1.A.2.2.4









Putative K+ channel

Bacteria
Cyanobacteria
K+ channel of Synechocystis PCC 6803
*1.A.2.2.5









Inward rectifier potassium channel
Bacteria
Proteobacteria
K+ channel of Burkholderia xenovorans