KCNH2_RAT
ID KCNH2_RAT Reviewed; 1163 AA.
AC O08962; O08720;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Potassium voltage-gated channel subfamily H member 2;
DE AltName: Full=Ether-a-go-go-related gene potassium channel 1;
DE Short=ERG-1;
DE Short=Eag-related protein 1;
DE Short=Ether-a-go-go-related protein 1;
DE Short=RERG;
DE Short=r-ERG;
DE AltName: Full=Voltage-gated potassium channel subunit Kv11.1;
GN Name=Kcnh2; Synonyms=Erg;
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].
RC TISSUE=Brain cortex;
RX PubMed=9664620;
RA Bauer C.K., Engeland B., Wulfsen I., Ludwig J., Pongs O., Schwarz J.R.;
RT "RERG is a molecular correlate of the inward-rectifying K current in clonal
RT rat pituitary cells.";
RL Recept. Channels 6:19-29(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 409-568.
RX PubMed=9012748; DOI=10.1161/01.res.80.2.261;
RA Wymore R.S., Gintant G.A., Wymore R.T., Dixon J.E., McKinnon D.,
RA Cohen I.S.;
RT "Tissue and species distribution of mRNA for the IKr-like K+ channel,
RT erg.";
RL Circ. Res. 80:261-268(1997).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=10718922; DOI=10.1046/j.1365-2826.2000.00447.x;
RA Wulfsen I., Hauber H.-P., Schiemann D., Bauer C.K., Schwarz J.R.;
RT "Expression of mRNA for voltage-dependent and inward-rectifying K channels
RT in GH3/B6 cells and rat pituitary.";
RL J. Neuroendocrinol. 12:263-272(2000).
RN [4]
RP INTERACTION WITH KCNH6 AND KCNH7, AND MUTAGENESIS OF GLY-630.
RX PubMed=11212207; DOI=10.1007/s004240000467;
RA Wimmers S., Wulfsen I., Bauer C.K., Schwarz J.R.;
RT "Erg1, erg2 and erg3 K channel subunits are able to form heteromultimers.";
RL Pflugers Arch. 441:450-455(2001).
RN [5]
RP INTERACTION WITH ALG10B.
RX PubMed=14525949; DOI=10.1096/fj.02-1057fje;
RA Kupershmidt S., Yang I.C.-H., Hayashi K., Wei J., Chanthaphaychith S.,
RA Petersen C.I., Johns D.C., George A.L. Jr., Roden D.M., Balser J.R.;
RT "The IKr drug response is modulated by KCR1 in transfected cardiac and
RT noncardiac cell lines.";
RL FASEB J. 17:2263-2265(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-285; SER-286 AND SER-353, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated inwardly
CC rectifying potassium channel. Channel properties are modulated by cAMP
CC and subunit assembly. Mediates the rapidly activating component of the
CC delayed rectifying potassium current in heart (IKr) (By similarity).
CC {ECO:0000250|UniProtKB:Q12809}.
CC -!- SUBUNIT: The potassium channel is probably composed of a homo- or
CC heterotetrameric complex of pore-forming alpha subunits that can
CC associate with modulating beta subunits (By similarity). Interacts with
CC DNAJB12 and DNAJB14; chaperones DNAJB12 and DNAJB14 promote
CC tetramerization (By similarity). Heteromultimer with KCNH6/ERG2 and
CC KCNH7/ERG3 (PubMed:11212207). Interacts with ALG10B (PubMed:14525949).
CC Heteromultimer with KCNE1 and KCNE2 (By similarity). Interacts with
CC CANX (By similarity). The core-glycosylated, but not the fully
CC glycosylated form interacts with RNF207 (By similarity). Interacts with
CC NDFIP1 and NDFIP2 (By similarity). {ECO:0000250|UniProtKB:Q12809,
CC ECO:0000269|PubMed:11212207, ECO:0000269|PubMed:14525949}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q12809};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and testis, slightly less
CC so in heart, adrenal, retina and thymus. Detected at lower levels in
CC lung, soleus, tibialis, and at very low levels in cornea and lens. A
CC shorter transcript is detected in skeletal muscle. Found in pituitary.
CC {ECO:0000269|PubMed:10718922}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position.
CC -!- PTM: Phosphorylated on serine and threonine residues. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the potassium channel family. H (Eag) (TC
CC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily. {ECO:0000305}.
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DR EMBL; Z96106; CAB09536.1; -; mRNA.
DR EMBL; U75210; AAC53160.1; -; mRNA.
DR RefSeq; NP_446401.1; NM_053949.1.
DR AlphaFoldDB; O08962; -.
DR BMRB; O08962; -.
DR SMR; O08962; -.
DR BioGRID; 250619; 2.
DR CORUM; O08962; -.
DR IntAct; O08962; 1.
DR STRING; 10116.ENSRNOP00000013800; -.
DR GuidetoPHARMACOLOGY; 572; -.
DR GlyGen; O08962; 1 site.
DR iPTMnet; O08962; -.
DR PhosphoSitePlus; O08962; -.
DR PaxDb; O08962; -.
DR GeneID; 117018; -.
DR KEGG; rno:117018; -.
DR CTD; 3757; -.
DR RGD; 621414; Kcnh2.
DR eggNOG; KOG0498; Eukaryota.
DR InParanoid; O08962; -.
DR OrthoDB; 247304at2759; -.
DR PhylomeDB; O08962; -.
DR Reactome; R-RNO-1296072; Voltage gated Potassium channels.
DR Reactome; R-RNO-5576890; Phase 3 - rapid repolarisation.
DR PRO; PR:O08962; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:RGD.
DR GO; GO:1902937; C:inward rectifier potassium channel complex; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISO:RGD.
DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; ISO:RGD.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:RGD.
DR GO; GO:0005216; F:ion channel activity; IDA:RGD.
DR GO; GO:0005267; F:potassium channel activity; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:RGD.
DR GO; GO:1902282; F:voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0086010; P:membrane depolarization during action potential; ISO:RGD.
DR GO; GO:0086009; P:membrane repolarization; ISO:RGD.
DR GO; GO:0086011; P:membrane repolarization during action potential; ISO:RGD.
DR GO; GO:0086013; P:membrane repolarization during cardiac muscle cell action potential; ISO:RGD.
DR GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; ISO:RGD.
DR GO; GO:1903765; P:negative regulation of potassium ion export across plasma membrane; ISO:RGD.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:RGD.
DR GO; GO:0055075; P:potassium ion homeostasis; ISO:RGD.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:RGD.
DR GO; GO:0060306; P:regulation of membrane repolarization; ISO:RGD.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISO:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISO:RGD.
DR CDD; cd00038; CAP_ED; 1.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG.
DR InterPro; IPR003967; K_chnl_volt-dep_ERG.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR000700; PAS-assoc_C.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF13426; PAS_9; 1.
DR PRINTS; PR01463; EAGCHANLFMLY.
DR PRINTS; PR01470; ERGCHANNEL.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00086; PAC; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS50113; PAC; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Methylation; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1163
FT /note="Potassium voltage-gated channel subfamily H member
FT 2"
FT /id="PRO_0000054003"
FT TOPO_DOM 1..405
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 406..426
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 427..452
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..473
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 519..522
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 523..543
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 544..549
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 550..570
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 571..613
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 614..634
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 635..640
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 641..661
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 662..1163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 17..88
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 92..144
FT /note="PAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141"
FT REGION 235..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 873..992
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1015..1043
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1126..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 626..631
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 256..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 933..951
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 744..861
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 873
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 1018
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 1141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 630
FT /note="G->S: Dominant negative mutant; abolishes ERG
FT current."
FT /evidence="ECO:0000269|PubMed:11212207"
FT CONFLICT 411
FT /note="V -> A (in Ref. 2; AAC53160)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1163 AA; 126952 MW; F0D75B0B532D9EA2 CRC64;
MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM
QRPCTCDFLH GPRTQRRAAA QIAQALLGAE ERKVEIAFYR KDGSCFLCLV DVVPVKNEDG
AVIMFILNFE VVMEKDMVGS PAHDTNHRGP STSWLASGRA KTFRLKLPAL LALTARESPM
RTGSTGSPGA PGAVVVDVDL TPAAPSSESL ALDEVSAMDN HVAGLGPAEE RRALVGPASA
SPVASIPGPH PSPRAQSLNP DASGSSCSLA RTRSRESCAS VRRASSADDI EAMRAGALPL
PPRHASTGAM HPLRSGLLNS TSDSDLVRYR TISKIPQITL NFVDLKGDPF LASPTSDREI
IAPKIKERTH NVTEKVTQVL SLGADVLPEY KLQAPRIHRW TILHYSPFKA VWDWLILLLV
IYTAVFTPYS AAFLLKETED GSQAPDCGYA CQPLAVVDLL VDIMFIVDIL INFRTTYVNA
NEEVVSHPGR IAVHYFKGWF LIDMVAAIPF DLLIFGSGSE ELIGLLKTAR LLRLVRVARK
LDRYSEYGAA VLFLLMCTFA LIAHWLACIW YAIGNMEQPH MDSHIGWLHN LGDQIGKPYN
SSGLGGPSIK DKYVTALYFT FSSLTSVGFG NVSPNTNSEK IFSICVMLIG SLMYASIFGN
VSAIIQRLYS GTARYHTQML RVREFIRFHQ IPNPLRQRLE EYFQHAWSYT NGIDMNAVLK
GFPECLQADI CLHLNRSLLQ HCKPFRGATK GCLRALAMKF KTTHAPPGDT LVHAGDLLTA
LYFISRGSIE ILRGDVVVAI LGKNDIFGEP LNLYARPGKS NGDVRALTYC DLHKIHRDDL
LEVLDMYPEF SDHFWSSLEI TFNLRDTNMI PGSPSSAELE SGFNRQRKRK LSFRRRTDKD
TEQPGEVSAL GQGPARVGPG PSCRGQPGGP WGESPSSGPS SPESSEDEGP GRSSSPLRLV
PFSSPRPPGD SPGGEPLTED GEKSSDTCNP LSGAFSGVSN IFSFWGDSRG RQYQELPRCP
APAPSLLNIP LSSPGRRSRG DVESRLDALQ RQLNRLETRL SADMATVLQL LQRQMTLVPP
AYSAVTTPGP GPTSTSPLLP VGPVPTLTLD SLSQVSQFVA FEELPAGAPE LPQDGPTRRL
SLPGQLGALT SQPLHRHGSD PGS
