ID   KCNJ2_RABIT             Reviewed;         427 AA.
AC   P49656;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   02-SEP-2026, entry version 157.
DE   RecName: Full=Inward rectifier potassium channel 2;
DE   AltName: Full=Inward rectifier K(+) channel Kir2.1;
DE            Short=IRK-1;
DE   AltName: Full=Potassium channel, inwardly rectifying subfamily J member 2;
GN   Name=KCNJ2; Synonyms=IRK1;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RC   STRAIN=New Zealand white; TISSUE=Heart;
RX   PubMed=8307148; DOI=10.1016/0014-5793(94)80126-6;
RA   Ishii K., Yamagishi T., Taira N.;
RT   "Cloning and functional expression of a cardiac inward rectifier K+
RT   channel.";
RL   FEBS Lett. 338:107-111(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RC   STRAIN=New Zealand white; TISSUE=Lens epithelium;
RX   PubMed=9533862; DOI=10.1006/exer.1997.0432;
RA   Rae J.L., Shepard A.R.;
RT   "Inwardly rectifying potassium channels in lens epithelium are from the
RT   IRK1 (Kir 2.1) family.";
RL   Exp. Eye Res. 66:347-359(1998).
CC   -!- FUNCTION: Inward rectifier potassium channels are characterized by a
CC       greater tendency to allow potassium to flow into the cell rather than
CC       out of it. Their voltage dependence is regulated by the concentration
CC       of extracellular potassium; as external potassium is raised, the
CC       voltage range of the channel opening shifts to more positive voltages.
CC       The inward rectification is mainly due to the blockage of outward
CC       current by internal magnesium (PubMed:8307148, PubMed:9533862). Can be
CC       blocked by extracellular barium and cesium (PubMed:8307148). Probably
CC       participates in establishing action potential waveform and excitability
CC       of neuronal and muscle tissues (By similarity).
CC       {ECO:0000250|UniProtKB:P63252, ECO:0000269|PubMed:8307148,
CC       ECO:0000269|PubMed:9533862}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103;
CC         Evidence={ECO:0000269|PubMed:8307148, ECO:0000269|PubMed:9533862};
CC   -!- ACTIVITY REGULATION: Activated by phosphatidylinositol 4,5 biphosphate
CC       (PtdIns(4,5)P2). {ECO:0000250|UniProtKB:Q64273}.
CC   -!- SUBUNIT: Homotetramer. Homomultimeric and heteromultimeric association
CC       with KCNJ4/Kir2.3. Can form heteromeric channels with Kir2.6/KCNJ18 (By
CC       similarity). Associates, via its PDZ-recognition domain, with a complex
CC       containing LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1.
CC       {ECO:0000250|UniProtKB:P63252, ECO:0000250|UniProtKB:Q64273}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O19182};
CC       Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma,
CC       T-tubule {ECO:0000250|UniProtKB:Q64273}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the ventricle and skeletal
CC       muscle, moderately in cerebrum and cerebellum. Only low levels are
CC       detected in kidney or lung.
CC   -!- PTM: S-nitrosylation increases the open probability and inward
CC       rectifying currents. {ECO:0000250|UniProtKB:P63252}.
CC   -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel
CC       (TC 1.A.2.1) family. KCNJ2 subfamily. {ECO:0000305}.
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DR   EMBL; D21057; BAA04636.1; -; mRNA.
DR   EMBL; AF021138; AAB88796.1; -; mRNA.
DR   PIR; S41087; S41087.
DR   RefSeq; NP_001075667.1; NM_001082198.1.
DR   RefSeq; XP_017204295.1; XM_017348806.3.
DR   AlphaFoldDB; P49656; -.
DR   SMR; P49656; -.
DR   FunCoup; P49656; 164.
DR   STRING; 9986.ENSOCUP00000008971; -.
DR   PaxDb; 9986-ENSOCUP00000008971; -.
DR   Ensembl; ENSOCUT00000010415.2; ENSOCUP00000008971.2; ENSOCUG00000010416.2.
DR   GeneID; 100008987; -.
DR   KEGG; ocu:100008987; -.
DR   CTD; 3759; -.
DR   eggNOG; KOG3827; Eukaryota.
DR   GeneTree; ENSGT01030000234586; -.
DR   HOGENOM; CLU_022738_3_0_1; -.
DR   InParanoid; P49656; -.
DR   OMA; THPEMDH; -.
DR   OrthoDB; 273257at2759; -.
DR   Proteomes; UP000001811; Chromosome 19.
DR   Bgee; ENSOCUG00000010416; Expressed in heart and 14 other cell types or tissues.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0030315; C:T-tubule; ISS:UniProtKB.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR   GO; GO:0086008; F:voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization; IEA:Ensembl.
DR   GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IEA:Ensembl.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IEA:Ensembl.
DR   GO; GO:0006813; P:potassium ion transport; ISS:UniProtKB.
DR   GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR   GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IEA:Ensembl.
DR   GO; GO:0060306; P:regulation of membrane repolarization; IEA:Ensembl.
DR   GO; GO:0034765; P:regulation of monoatomic ion transmembrane transport; IEA:TreeGrafter.
DR   GO; GO:0014861; P:regulation of skeletal muscle contraction via regulation of action potential; IEA:Ensembl.
DR   GO; GO:0055119; P:relaxation of cardiac muscle; IEA:Ensembl.
DR   GO; GO:0090076; P:relaxation of skeletal muscle; IEA:Ensembl.
DR   FunFam; 1.10.287.70:FF:000039; ATP-sensitive inward rectifier potassium channel 12; 1.
DR   FunFam; 2.60.40.1400:FF:000001; G protein-activated inward rectifier potassium channel 2; 1.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 2.60.40.1400; G protein-activated inward rectifier potassium channel 1; 1.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR041647; IRK_C.
DR   InterPro; IPR016449; K_chnl_inward-rec_Kir.
DR   InterPro; IPR003271; K_chnl_inward-rec_Kir2.1.
DR   InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR   InterPro; IPR013673; K_chnl_inward-rec_Kir_N.
DR   InterPro; IPR040445; Kir_TM.
DR   PANTHER; PTHR11767; INWARD RECTIFIER POTASSIUM CHANNEL; 1.
DR   PANTHER; PTHR11767:SF43; INWARD RECTIFIER POTASSIUM CHANNEL 2; 1.
DR   Pfam; PF01007; IRK; 1.
DR   Pfam; PF17655; IRK_C; 1.
DR   Pfam; PF08466; IRK_N; 1.
DR   PIRSF; PIRSF005465; GIRK_kir; 1.
DR   PRINTS; PR01324; KIR21CHANNEL.
DR   PRINTS; PR01320; KIRCHANNEL.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Ion channel; Ion transport; Membrane; Potassium;
KW   Potassium transport; Reference proteome; S-nitrosylation; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..427
FT                   /note="Inward rectifier potassium channel 2"
FT                   /id="PRO_0000154927"
FT   TOPO_DOM        1..81
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        82..106
FT                   /note="Helical; Name=M1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        107..128
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        129..140
FT                   /note="Helical; Pore-forming; Name=H5"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        141..147
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        148..156
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        157..178
FT                   /note="Helical; Name=M2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        179..427
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          181..208
FT                   /note="Polyphosphoinositide (PIP2)-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q64273"
FT   REGION          384..427
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           142..147
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   MOTIF           425..427
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000255"
FT   SITE            172
FT                   /note="Role in the control of polyamine-mediated channel
FT                   gating and in the blocking by intracellular magnesium"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         76
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P63252"
SQ   SEQUENCE   427 AA;  48350 MW;  1A57A8BB19B8A4A3 CRC64;
     MGSVRTNRYS IVSSEEDGMK LATMAVANGF GNGKSKVHTR QQCRSRFVKK DGHCNVQFIN
     VGEKGQRYLA DIFTTCVDIR WRWMLVIFCL AFVLSWLFFG CVFWLIALLH GDLDASRESK
     ACVSEVNSFT AAFLFSIETQ TTIGYGFRCV TDECPVAVFM VVFQSIVGCI IDAFIIGAVM
     AKMAKPKKRN ETLVFSHNAV IAMRDGKLCL MWRVGNLRKS HLVEAHVRAQ LLKSRITSEG
     EYIPLDQIDI NVGFDSGIDR IFLVSPITIV HEIDEDSPLY DLSKQDMDNA DFEIVVILEG
     MVEATAMTTQ CRSSYLANEI LWGHRYEPVL FEEKHYYKVD YSRFHKTYEV PNTPLCSARD
     LAEKKYILSN ANSFCYENEV ALTSKEEDDS ENGVPESTST DTPPDIDLHN QASVPLEPRP
     LRRESEI
//