KCNH2_MOUSE
ID KCNH2_MOUSE Reviewed; 1162 AA.
AC O35219; O35220; O35221; O35989;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 184.
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=MERG;
DE AltName: Full=Voltage-gated potassium channel subunit Kv11.1;
GN Name=Kcnh2; Synonyms=Erg, Merg1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), AND
RP VARIANTS ARG-186; THR-455; TYR-752 AND ASN-1006.
RC STRAIN=129/Sv, and BALB/cJ; TISSUE=Heart;
RX PubMed=9351462; DOI=10.1161/01.res.81.5.870;
RA London B., Trudeau M.C., Newton K.P., Beyer A.K., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Satler C.A., Robertson G.A.;
RT "Two isoforms of the mouse ether-a-go-go-related gene coassemble to form
RT channels with properties similar to the rapidly activating component of the
RT cardiac delayed rectifier K+ current.";
RL Circ. Res. 81:870-878(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Atrial tumor;
RX PubMed=9351446; DOI=10.1161/01.res.81.5.719;
RA Lees-Miller J.P., Kondo C., Wang L., Duff H.J.;
RT "Electrophysiological characterization of an alternatively processed ERG K+
RT channel in mouse and human hearts.";
RL Circ. Res. 81:719-726(1997).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241; SER-245; SER-285;
RP SER-286; SER-322; SER-873; SER-876 AND SER-1140, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1017, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1; Synonyms=1A, A;
CC IsoId=O35219-1; Sequence=Displayed;
CC Name=2; Synonyms=1A';
CC IsoId=O35219-2; Sequence=VSP_000969;
CC Name=3; Synonyms=1B, B;
CC IsoId=O35219-3; Sequence=VSP_000970;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in heart, brain and testis
CC and at low levels in lung. Isoform 3 is expressed predominantly in
CC heart. The expression of isoform 2 is low in all tissues tested.
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; AF012868; AAC53418.1; -; mRNA.
DR EMBL; AF012869; AAC53419.1; -; mRNA.
DR EMBL; AF012871; AAC53420.1; -; Genomic_DNA.
DR EMBL; AF012870; AAC53420.1; JOINED; Genomic_DNA.
DR EMBL; AF012871; AAC53421.1; -; Genomic_DNA.
DR EMBL; AF012871; AAC53422.1; -; Genomic_DNA.
DR EMBL; AF012870; AAC53422.1; JOINED; Genomic_DNA.
DR EMBL; AF034762; AAB87571.1; -; mRNA.
DR CCDS; CCDS19116.1; -. [O35219-1]
DR CCDS; CCDS80224.1; -. [O35219-3]
DR RefSeq; NP_001281091.1; NM_001294162.1.
DR AlphaFoldDB; O35219; -.
DR BMRB; O35219; -.
DR SMR; O35219; -.
DR ComplexPortal; CPX-3197; Voltage-gated potassium channel complex variant 2.
DR ComplexPortal; CPX-3198; Voltage-gated potassium channel complex variant 1.
DR IntAct; O35219; 31.
DR STRING; 10090.ENSMUSP00000047705; -.
DR GlyGen; O35219; 1 site.
DR iPTMnet; O35219; -.
DR PhosphoSitePlus; O35219; -.
DR jPOST; O35219; -.
DR MaxQB; O35219; -.
DR PaxDb; O35219; -.
DR PeptideAtlas; O35219; -.
DR PRIDE; O35219; -.
DR ProteomicsDB; 269265; -. [O35219-1]
DR ProteomicsDB; 269266; -. [O35219-2]
DR ProteomicsDB; 269267; -. [O35219-3]
DR DNASU; 16511; -.
DR GeneID; 16511; -.
DR KEGG; mmu:16511; -.
DR UCSC; uc008wrb.1; mouse. [O35219-3]
DR CTD; 3757; -.
DR MGI; MGI:1341722; Kcnh2.
DR eggNOG; KOG0498; Eukaryota.
DR InParanoid; O35219; -.
DR PhylomeDB; O35219; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR Reactome; R-MMU-5576890; Phase 3 - rapid repolarisation.
DR BioGRID-ORCS; 16511; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Erg; mouse.
DR PRO; PR:O35219; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O35219; protein.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:1902937; C:inward rectifier potassium channel complex; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISO:MGI.
DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; ISO:MGI.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:MGI.
DR GO; GO:0005216; F:ion channel activity; ISO:MGI.
DR GO; GO:0005267; F:potassium channel activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:MGI.
DR GO; GO:1902282; F:voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; ISO:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0086010; P:membrane depolarization during action potential; ISO:MGI.
DR GO; GO:0086009; P:membrane repolarization; ISO:MGI.
DR GO; GO:0086011; P:membrane repolarization during action potential; ISO:MGI.
DR GO; GO:0086013; P:membrane repolarization during cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:1903765; P:negative regulation of potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:0055075; P:potassium ion homeostasis; ISO:MGI.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:MGI.
DR GO; GO:0006813; P:potassium ion transport; ISO:MGI.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IDA:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:MGI.
DR GO; GO:0060306; P:regulation of membrane repolarization; ISO:MGI.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IDA:MGI.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISO:MGI.
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 Alternative splicing; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Methylation; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1162
FT /note="Potassium voltage-gated channel subfamily H member
FT 2"
FT /id="PRO_0000054000"
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..1162
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 233..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 873..991
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1125..1162
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 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08962"
FT MOD_RES 873
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1017
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..378
FT /note="MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELC
FT GYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVD
FT VVPVKNEDGAVIMFILNFEVVMEKDMVGSPAHDTNHRGPSTSWLASGRAKTFRLKLPAL
FT LALTARESSVRTGSMHSAGAPGAVVVDVDLTPAAPSSESLALDEVSAMDNHVAGLGPAE
FT ERRALVGPGSASPVASIRGPHPSPRAQSLNPDASGSSCSLARTRSRESCASVRRASSAD
FT DIEAMRAGALPPPPRHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKG
FT DPFLASPTSDREIIAPKIKERTHNVTEKVTQ -> MAIPTGKESRTGALQPRAQKGRVR
FT RAVRISSLVAQE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9351446,
FT ECO:0000303|PubMed:9351462"
FT /id="VSP_000970"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9351462"
FT /id="VSP_000969"
FT VARIANT 186
FT /note="H -> R (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:9351462"
FT VARIANT 455
FT /note="A -> T (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:9351462"
FT VARIANT 752
FT /note="C -> Y (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:9351462"
FT VARIANT 1006
FT /note="D -> N (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:9351462"
SQ SEQUENCE 1162 AA; 126886 MW; A9455F7F10B61E46 CRC64;
MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM
QRPCTCDFLH GPRTQRRAAA QIAQALLGAE ERKVEIAFYR KDGSCFLCLV DVVPVKNEDG
AVIMFILNFE VVMEKDMVGS PAHDTNHRGP STSWLASGRA KTFRLKLPAL LALTARESSV
RTGSMHSAGA PGAVVVDVDL TPAAPSSESL ALDEVSAMDN HVAGLGPAEE RRALVGPGSA
SPVASIRGPH PSPRAQSLNP DASGSSCSLA RTRSRESCAS VRRASSADDI EAMRAGALPP
PPRHASTGAM HPLRSGLLNS TSDSDLVRYR TISKIPQITL NFVDLKGDPF LASPTSDREI
IAPKIKERTH NVTEKVTQVL SLGADVLPEY KLQAPRIHRW TILHYSPFKA VWDWLILLLV
IYTAVFTPYS AAFLLKETED GSQAPDCGYA CQPLAVVDLI 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 PGSPGSAELE SGFNRQRKRK LSFRRRTDKD
TEQPGEVSAL GQGPARVGPG PSCRGQPGGP WGESPSSGPS SPESSEDEGP GRSSSPLRLV
PFSSPRPPGD PPGGEPLTED GEKSDTCNPL SGAFSGVSNI FSFWGDSRGR QYQELPRCPA
PAPSLLNIPL SSPGRRSRGD VESRLDALQR QLNRLETRLS ADMATVLQLL QRQMTLVPPA
YSAVTTPGPG PTSASPLLPV GPVPTLTLDS LSQVSQFVAF EELPAGAPEL PQDGPTRRLS
LPGQLGALTS QPLHRHGSDP GS
