KCNH2_CANLF
ID KCNH2_CANLF Reviewed; 1158 AA.
AC Q9TSZ3; O02719; O18820;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
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=DERG;
DE Short=ERG-1;
DE Short=Eag-related protein 1;
DE Short=Ether-a-go-go-related protein 1;
DE Short=c-ERG;
DE AltName: Full=Voltage-gated potassium channel subunit Kv11.1;
GN Name=KCNH2; Synonyms=CERG, ERG;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=11417212; DOI=10.1007/s004240100524;
RA Zehelein J., Zhang W., Koenen M., Graf M., Heinemann S.H., Katus H.A.;
RT "Molecular cloning and expression of cERG, the ether a go-go-related gene
RT from canine myocardium.";
RL Pflugers Arch. 442:188-191(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 407-566.
RC TISSUE=Heart;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 616-714.
RC TISSUE=Heart atrium;
RX PubMed=10205145; DOI=10.1161/01.res.84.7.776;
RA Yue L., Melnyk P., Gaspo R., Wang Z., Nattel S.;
RT "Molecular mechanisms underlying ionic remodeling in a dog model of atrial
RT fibrillation.";
RL Circ. Res. 84:776-784(1999).
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. Interacts with DNAJB12 and
CC DNAJB14; chaperones DNAJB12 and DNAJB14 promote tetramerization (By
CC similarity). Heteromultimer with KCNH6/ERG2 and KCNH7/ERG3 (By
CC similarity). Interacts with ALG10B (By similarity). Heteromultimer with
CC KCNE1 and KCNE2. Interacts with CANX. The core-glycosylated, but not
CC the fully glycosylated form interacts with RNF207. Interacts with
CC NDFIP1 and NDFIP2 (By similarity). {ECO:0000250|UniProtKB:O08962,
CC ECO:0000250|UniProtKB:Q12809}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q12809};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in left and right atria of the
CC heart, in cortex and hippocampus; detected at intermediate levels in
CC left and right ventricle, Purkinje fibers, cerebellum, thalamus and
CC basal ganglia; detected at low levels in liver, spleen and kidney.
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; AJ243344; CAB64868.1; -; mRNA.
DR EMBL; U75213; AAC48722.1; -; mRNA.
DR EMBL; AF017429; AAB70524.1; -; mRNA.
DR RefSeq; NP_001003145.1; NM_001003145.1.
DR AlphaFoldDB; Q9TSZ3; -.
DR BMRB; Q9TSZ3; -.
DR SMR; Q9TSZ3; -.
DR STRING; 9612.ENSCAFP00000035370; -.
DR BindingDB; Q9TSZ3; -.
DR ChEMBL; CHEMBL3085616; -.
DR PaxDb; Q9TSZ3; -.
DR Ensembl; ENSCAFT00000039504; ENSCAFP00000035367; ENSCAFG00000025442.
DR Ensembl; ENSCAFT00030045812; ENSCAFP00030040025; ENSCAFG00030024832.
DR Ensembl; ENSCAFT00040008538; ENSCAFP00040007416; ENSCAFG00040004496.
DR Ensembl; ENSCAFT00845017520; ENSCAFP00845013635; ENSCAFG00845009911.
DR GeneID; 403761; -.
DR KEGG; cfa:403761; -.
DR CTD; 3757; -.
DR VEuPathDB; HostDB:ENSCAFG00845009911; -.
DR VGNC; VGNC:42248; KCNH2.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000159846; -.
DR InParanoid; Q9TSZ3; -.
DR OrthoDB; 247304at2759; -.
DR Proteomes; UP000002254; Chromosome 16.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:1902937; C:inward rectifier potassium channel complex; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; IEA:Ensembl.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IEA:Ensembl.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0097110; F:scaffold protein binding; IEA:Ensembl.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:1902282; F:voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0086010; P:membrane depolarization during action potential; IEA:Ensembl.
DR GO; GO:0086011; P:membrane repolarization during action potential; IBA:GO_Central.
DR GO; GO:1903765; P:negative regulation of potassium ion export across plasma membrane; IEA:Ensembl.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; IEA:Ensembl.
DR GO; GO:0055075; P:potassium ion homeostasis; IEA:Ensembl.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IBA:GO_Central.
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 2: Evidence at transcript 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..1158
FT /note="Potassium voltage-gated channel subfamily H member
FT 2"
FT /id="PRO_0000053997"
FT TOPO_DOM 1..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..449
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..494
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..519
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 520..540
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 541..546
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 547..567
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 568..610
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 611..631
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 632..637
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..658
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 659..1158
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 232..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 869..987
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 623..628
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 256..279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 929..946
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 741..858
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 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08962"
FT MOD_RES 870
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT MOD_RES 873
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 1013
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O35219"
FT MOD_RES 1136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12809"
FT CARBOHYD 597
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 442
FT /note="P -> T (in Ref. 2; AAC48722)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1158 AA; 126645 MW; 53C849032B4AA3D0 CRC64;
MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM
QRPCTCDFLH GPRTQRRAAA QIAQALLGAE ERKVEIAFYR KDGSCFLCLV DVVPVKNEDG
AVIMFILNFE VVMEKDMVGS PTHDTNHRGP PTSWLAPGRA KTFRLKLPAL LALTTRESSA
RPGGVGSAGA PGAVVVDVDL SPAVPSRESL ALDEVTAMDN HVAGLGPMEE QRALVGSSSP
PAGAPEPLPS PRAHSLNPDA SGSSCSLART RSRESCASVR RASSADDIEA MRAGLPPPPR
HASTGAMHPL RGGLLNSTSD SDLVRYRTIS KIPQITLNFV DLKGDPFLAS PTSDREIIAP
KIKERTHNVT EKVTQVLSLG ADVLPEYKLQ APRIHRWTIL HYSPFKAVWD WLILLLVIYT
AVFTPYSAAF LLKETEEGPP APDCGYACQP LAVVDFIVDI MFIVDILINF RTTYVNANEE
VVSHPGRIAV HYFKGWFLID MVAAIPFDLL IFGSGSEELI GLLKTARLLR LVRVARKLDR
YSEYGAAVLF LLMCTFALIA HWLACIWYAI GNMEQPHMDS RIGWLHNLGD QIGKPYNSSG
LGGPSIKDKY VTALYFTFSS LTSVGFGNVS PNTNSEKIFS ICVMLIGSLM YASIFGNVSA
IIQRLYSGTA RYHTQMLRVR EFIRFHQIPN PLRQRLEEYF QHAWSYTNGI DMNAVLKGFP
ECLQADICLH LNRSLLQHCK PFRGATKGCL RALAMKFKTT HAPPGDTLVH AGDLLTALYF
ISRGSIEILR GDVVVAILGK NDIFGEPLNL YARPGKSNGD VRALTYCDLH KIHRDDLLEV
LDMYPEFSDH FWSSLEITFN LRDTNMIPGS PGSAELEGGF NRQRKRKLSF RRRTDRDPEQ
PGEVSALGPG RAGAGPSGRG RPGGPWGESP SSGPSSPESS EDEGPGRSSS PLRLVPFSSP
RPPGEPPGGE PLTEDGEKSS DTCNPLSGAF SGVSNIFSFW GDSRGHQYQE LPRCPAPTPS
LLNIPLSSPC RRPRGDVEGR LDALQRQLNR LETRLSADMA TVLQLLQRQM TLIPPAYSAV
TTPGPGPTST SSLLPVSPIP TLTLDSLSQV SQFMAFEELP PGAPELPQDG PPRRLSLPGQ
LGALTSQPLH RHGSDPGS
