ID   KCNJ4_RAT               Reviewed;         446 AA.
AC   P52190; O35752;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   04-NOV-2026, entry version 170.
DE   RecName: Full=Inward rectifier potassium channel 4;
DE   AltName: Full=BIR11;
DE   AltName: Full=Brain inwardly rectifying K(+) channel 2;
DE   AltName: Full=Inward rectifier K(+) channel Kir2.3;
DE            Short=IRK-3;
DE   AltName: Full=Potassium channel, inwardly rectifying subfamily J member 4;
GN   Name=Kcnj4; Synonyms=Irk3;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RC   STRAIN=GH3/B6;
RX   PubMed=7796907; DOI=10.1016/0014-5793(95)00527-g;
RA   Falk T., Meyerhof W., Corrette B.J., Schaefer J., Bauer C.K., Schwarz J.R.,
RA   Richter D.;
RT   "Cloning, functional expression and mRNA distribution of an inwardly
RT   rectifying potassium channel protein.";
RL   FEBS Lett. 367:127-131(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=7874445;
RA   Bond C.T., Pessia M., Xia X.-M., Lagrutta A., Kavanaugh M.P., Adelman J.P.;
RT   "Cloning and expression of a family of inward rectifier potassium
RT   channels.";
RL   Recept. Channels 2:183-191(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=7624316; DOI=10.1073/pnas.92.15.6753;
RA   Bredt D.S., Wang T.L., Cohen N.A., Guggino W.B., Snyder S.H.;
RT   "Cloning and expression of two brain-specific inwardly rectifying potassium
RT   channels.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:6753-6757(1995).
RN   [4]
RP   ASSOCIATION WITH A COMPLEX CONTAINING CASK; LIN7A; LIN7B; LIN7C; APBA1 AND
RP   DLG1.
RX   PubMed=14960569; DOI=10.1074/jbc.m400284200;
RA   Leonoudakis D., Conti L.R., Radeke C.M., McGuire L.M., Vandenberg C.A.;
RT   "A multiprotein trafficking complex composed of SAP97, CASK, Veli, and
RT   Mint1 is associated with inward rectifier Kir2 potassium channels.";
RL   J. Biol. Chem. 279:19051-19063(2004).
RN   [5]
RP   TISSUE SPECIFICITY.
RX   PubMed=16855024; DOI=10.1091/mbc.e06-02-0129;
RA   Alewine C., Olsen O., Wade J.B., Welling P.A.;
RT   "TIP-1 has PDZ scaffold antagonist activity.";
RL   Mol. Biol. Cell 17:4200-4211(2006).
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. Can be blocked by extracellular barium
CC       and cesium. {ECO:0000269|PubMed:7624316, ECO:0000269|PubMed:7796907}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103;
CC         Evidence={ECO:0000269|PubMed:7624316, ECO:0000269|PubMed:7796907};
CC   -!- SUBUNIT: Homomultimeric and heteromultimeric association with KCNJ2 and
CC       KCNJ12 (By similarity). Interacts with DLG2 and DLG4 (By similarity).
CC       Associates, via its PDZ-recognition domain, with a complex containing
CC       LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 (PubMed:14960569). Interacts
CC       with TAX1BP3. TAX1BP3 competes with LIN7 family members for KCNJ4
CC       binding (By similarity). {ECO:0000250|UniProtKB:P48050,
CC       ECO:0000250|UniProtKB:P52189, ECO:0000269|PubMed:14960569}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14960569};
CC       Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC       {ECO:0000250|UniProtKB:P52189}. Postsynaptic cell membrane
CC       {ECO:0000250|UniProtKB:P52189}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=TAX1BP3 binding promotes dissociation of KCNJ4 from
CC       LIN7 family members and KCNJ4 internalization.
CC       {ECO:0000250|UniProtKB:P52189}.
CC   -!- TISSUE SPECIFICITY: Detected in kidney distal convoluted tubules (at
CC       protein level). Widely expressed throughout the brain. Also found in
CC       some peripheral tissues. {ECO:0000269|PubMed:16855024}.
CC   -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel
CC       (TC 1.A.2.1) family. KCNJ4 subfamily. {ECO:0000305}.
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DR   EMBL; X87635; CAA60963.1; -; mRNA.
DR   EMBL; X83580; CAA58563.1; -; mRNA.
DR   EMBL; U27582; AAA87812.1; -; mRNA.
DR   PIR; S66268; S66268.
DR   RefSeq; NP_446322.2; NM_053870.3.
DR   AlphaFoldDB; P52190; -.
DR   SMR; P52190; -.
DR   FunCoup; P52190; 694.
DR   STRING; 10116.ENSRNOP00000053014; -.
DR   GlyGen; P52190; 2 sites.
DR   iPTMnet; P52190; -.
DR   PhosphoSitePlus; P52190; -.
DR   PaxDb; 10116-ENSRNOP00000053014; -.
DR   GeneID; 116649; -.
DR   KEGG; rno:116649; -.
DR   UCSC; RGD:621436; rat.
DR   AGR; RGD:621436; -.
DR   CTD; 3761; -.
DR   RGD; 621436; Kcnj4.
DR   eggNOG; KOG3827; Eukaryota.
DR   InParanoid; P52190; -.
DR   OMA; AAEPCIM; -.
DR   OrthoDB; 273257at2759; -.
DR   PhylomeDB; P52190; -.
DR   Reactome; R-RNO-1296041; Activation of G protein gated Potassium channels.
DR   Reactome; R-RNO-1296053; Classical Kir channels.
DR   Reactome; R-RNO-5576886; Phase 4 - resting membrane potential.
DR   Reactome; R-RNO-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR   PRO; PR:P52190; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005886; C:plasma membrane; EXP:UniProtKB.
DR   GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0030165; F:PDZ domain binding; ISO:RGD.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
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; IPR003273; K_chnl_inward-rec_Kir2.3.
DR   InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR   InterPro; IPR040445; Kir_TM.
DR   PANTHER; PTHR11767; INWARD RECTIFIER POTASSIUM CHANNEL; 1.
DR   PANTHER; PTHR11767:SF53; INWARD RECTIFIER POTASSIUM CHANNEL 4; 1.
DR   Pfam; PF01007; IRK; 1.
DR   Pfam; PF17655; IRK_C; 1.
DR   PIRSF; PIRSF005465; GIRK_kir; 1.
DR   PRINTS; PR01326; KIR23CHANNEL.
DR   PRINTS; PR01320; KIRCHANNEL.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Cytoplasmic vesicle; Ion channel; Ion transport; Membrane;
KW   Postsynaptic cell membrane; Potassium; Potassium transport;
KW   Reference proteome; Synapse; Transmembrane; Transmembrane helix; Transport;
KW   Voltage-gated channel.
FT   CHAIN           1..446
FT                   /note="Inward rectifier potassium channel 4"
FT                   /id="PRO_0000154933"
FT   TOPO_DOM        1..55
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        56..80
FT                   /note="Helical; Name=M1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        81..120
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        121..132
FT                   /note="Helical; Pore-forming; Name=H5"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        133..139
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        140..148
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        149..170
FT                   /note="Helical; Name=M2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        171..446
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          91..111
FT                   /note="Val/Gly/Ala/Pro stretch"
FT   MOTIF           134..139
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   MOTIF           444..446
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000255"
FT   SITE            164
FT                   /note="Role in the control of polyamine-mediated channel
FT                   gating and in the blocking by intracellular magnesium"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        53..54
FT                   /note="Missing (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        91..98
FT                   /note="PSGPTAGG -> LRAHGGS (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        109
FT                   /note="T -> R (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        115..122
FT                   /note="IMHVNGFL -> YHACKRLFW (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        130..131
FT                   /note="ET -> GA (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        135
FT                   /note="I -> Y (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        155
FT                   /note="Missing (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        176
FT                   /note="P -> A (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        176
FT                   /note="P -> G (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        178
FT                   /note="P -> S (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        197..198
FT                   /note="DG -> T (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        205..207
FT                   /note="RVG -> GWV (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        294
FT                   /note="V -> A (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        298
FT                   /note="A -> V (in Ref. 2; CAA60963)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        308
FT                   /note="L -> Q (in Ref. 3; AAA87812)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   446 AA;  49690 MW;  A86073996861D20C CRC64;
     MHGHSRNGQA HVPRRKRRNR FVKKNGQCNV YFANLSNKSQ RYMADIFTTC VDTRWRYMLM
     IFSAAFLVSW LFFGLLFWCI AFFHGDLEPS PSGPTAGGPG GNGGGAAPTA AKPCIMHVNG
     FLGAFLFSVE TQTTIGYGFR CVTEECPLAV IAVVVQSIVG CVIDSFMIGT IMAKMPRPKK
     RAQTLLFSHH AVISVRDGKL CLMWRVGNLR KSHIVEAHVR AQLIKPYMTQ EGEYLPLDQR
     DLNVGYDIGL DRIFLVSPII IVHEIDEDSP LYGMGKEELE SEDFEIVVIL EGMVEATAMT
     TQARSSYLAS EILWGHRFEP VVFEEKSHYK VDYSRFHKTY EVAGTPCCSA RELQESKITV
     LPAPPPPPSA FCYENELALM SQEEEEMEEE AAAAAAVAAG LGLEAGSKEE TGIIRMLEFG
     SHLDLERMQA ATLPLDNISY RRESAI
//