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1.A.2.1.10
G-protein-activated inward rectifying K+ channel, Kir3.2, KATP2, KCNJ6, KCNJ7 or GIRK2 of 423 aas (Inanobe et al., 2011; Yokogawa et al. 2011). They play essential roles in electrical signaling in neurons and muscle cells (Weng et al. 2021), being 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 GIRK channels are activated by Ivermectin (IVM). Cholesterol binds to and upregulates GIRK channels (GIRK2 and 4), and the binding sites have been determined (Rosenhouse-Dantsker 2018). An inherited gain-of-function mutation in the human GIRK3.4 causes familial human sinus node dysfunction (SND). The increased activity of GIRK channels likely leads to a sustained hyperpolarization of pacemaker cells and thereby reduces heart rate (Kuß et al. 2019). GIRK2 channels are abundantly expressed in the heart and require that phosphatidylinositol bisphosphate (PIP2) is present so that intracellular channel-gating regulators such as Gbetagamma (Gβγ) and Na+ ions maintain the channel-open state. Li et al. 2019 determined how each regulator uses  channel domain movements to control gate transitions. Na+ controls the cytosolic gate of the channel through an anti-clockwise rotation, whereas Gβγ stabilizes the transmembrane gate in the open state through a rocking movement of the cytosolic domain. Both effects altered the way by which the channel interacts with PIP2 and thereby stabilized the open states of the respective gates (Li et al. 2019). The protein plays a role in heart atrial fibrillation (AF)-valvular heart disease (VHD) (Zhao et al. 2021). Measurements of ligand binding and channel current have been made (Usher et al. 2021). CryoEM structures of GIRK2 in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS) and phosphatidylinositol 4,5-bisphosphate (PIP2) reveal that CHS binds near PIP2 in lipid-facing hydrophobic pockets of the transmembrane domain, suggesting that CHS stabilizes the PIP2 interaction with the channel to promote engagement of the cytoplasmic domain with the transmembrane region (Mathiharan et al. 2021).

Accession Number:P48051
Protein Name:G protein-activated inward rectifier potassium channel 2
Length:423
Molecular Weight:48451.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:3
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Entrez Gene ID: 3763   
Pfam: PF01007   
KEGG: hsa:3763   

Gene Ontology

GO:0005794 C:Golgi apparatus
GO:0008076 C:voltage-gated potassium channel complex
GO:0015467 F:G-protein activated inward rectifier potassium channel activity
GO:0007268 P:synaptic transmission

References (5)

[1] “Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels.”  Ferrer J.et.al.   7592809
[2] “Co-expression of human Kir3 subunits can yield channels with different functional properties.”  Schoots O.et.al.   10659995
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit.”  Sakura H.et.al.   7796919
[5] “Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM.”  Tsaur M.-L.et.al.   7729621
Structure:
3sya   3syc   3syp     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAKLTESMTN VLEGDSMDQD VESPVAIHQP KLPKQARDDL PRHISRDRTK RKIQRYVRKD 
61:	GKCNVHHGNV RETYRYLTDI FTTLVDLKWR FNLLIFVMVY TVTWLFFGMI WWLIAYIRGD 
121:	MDHIEDPSWT PCVTNLNGFV SAFLFSIETE TTIGYGYRVI TDKCPEGIIL LLIQSVLGSI 
181:	VNAFMVGCMF VKISQPKKRA ETLVFSTHAV ISMRDGKLCL MFRVGDLRNS HIVEASIRAK 
241:	LIKSKQTSEG EFIPLNQTDI NVGYYTGDDR LFLVSPLIIS HEINQQSPFW EISKAQLPKE 
301:	ELEIVVILEG MVEATGMTCQ ARSSYITSEI LWGYRFTPVL TLEDGFYEVD YNSFHETYET 
361:	STPSLSAKEL AELASRAELP LSWSVSSKLN QHAELETEEE EKNLEEQTER NGDVANLENE 
421:	SKV