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1.A.2.1.10
G-protein-activated inward rectifying K+ channel, Kir3.2, KATP2, KCNJ7 or GIRK2 of 423 aas (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  Ivermectin (IVM) directly.  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 is likely to lead 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 the channel domain movements to control gate transitions. Na+ controls the cytosolic gate of the channel through an anti-clockwise rotation, whereas Gbetagamma 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).

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:

Genevestigator: P48051
eggNOG: prNOG19724
HEGENOM: HBG716702
Entrez Gene ID: 3763   
Pfam: PF01007   
Drugbank: Drugbank Link   
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     

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

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