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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). A cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug, glibenclamide, and ATP at 3.63 A resolution revealed details of the ATP and glibenclamide binding sites (Martin et al. 2017). The structure showed that glibenclamide lodges in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide led to reduced sensitivity to this drug (Martin et al. 2017).

Accession Number:P70673
Protein Name:ATP-sensitive inward rectifier potassium channel 11 aka ROMK aka Kcnj11 aka Kir6.2
Length:390
Molecular Weight:43608.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:3
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: P70673
eggNOG: maNOG08055
RefSeq: NP_112648.2   
Entrez Gene ID: 83535   
Pfam: PF01007   
KEGG: rno:83535   

Gene Ontology

GO:0008282 C:ATP-sensitive potassium channel complex
GO:0005783 C:endoplasmic reticulum
GO:0005792 C:microsome
GO:0005739 C:mitochondrion
GO:0030315 C:T-tubule
GO:0015272 F:ATP-activated inward rectifier potassium ch...
GO:0008022 F:protein C-terminus binding
GO:0042493 P:response to drug
GO:0033574 P:response to testosterone stimulus

References (2)

[1] “A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.”  Isomoto S.et.al.   8798681
[2] “Rat inwardly rectifying potassium channel Kir6.2: cloning electrophysiological characterization, and decreased expression in pancreatic islets of male Zucker diabetic fatty rats.”  Tokuyama Y.et.al.   8607800

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLSRKGIIPE EYVLTRLAED PTEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF 
61:	TTLVDLKWPH TLLIFTMSFL CSWLLFAMVW WLIAFAHGDL APGEGTNVPC VTSIHSFSSA 
121:	FLFSIEVQVT IGFGGRMVTE ECPLAILILI VQNIVGLMIN AIMLGCIFMK TAQAHRRAET 
181:	LIFSKHAVIT LRHGRLCFML RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM 
241:	ENGVGGNSIF LVAPLIIYHV IDSNSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA 
301:	RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTVKVP TPLCTARQLD EDRSLLDALT 
361:	LASSRGPLRK RSVAVAKAKP KFSISPDSLS