ID   KCNH6_RAT               Reviewed;         950 AA.
AC   O54853;
DT   28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   24-JAN-2024, entry version 165.
DE   RecName: Full=Potassium voltage-gated channel subfamily H member 6;
DE   AltName: Full=Ether-a-go-go-related gene potassium channel 2;
DE            Short=ERG-2;
DE            Short=Eag-related protein 2;
DE            Short=Ether-a-go-go-related protein 2;
DE   AltName: Full=Voltage-gated potassium channel subunit Kv11.2;
GN   Name=Kcnh6; Synonyms=Erg2;
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=Cervical ganglion;
RX   PubMed=9390998; DOI=10.1523/jneurosci.17-24-09423.1997;
RA   Shi W., Wymore R.S., Wang H.-S., Pan Z., Cohen I.S., McKinnon D.,
RA   Dixon J.E.;
RT   "Identification of two nervous system-specific members of the erg potassium
RT   channel gene family.";
RL   J. Neurosci. 17:9423-9432(1997).
RN   [2]
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   [3]
RP   INTERACTION WITH KCNH2 AND KCNH7, AND MUTAGENESIS OF GLY-480.
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   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=11425889; DOI=10.1523/jneurosci.21-13-04609.2001;
RA   Saganich M.J., Machado E., Rudy B.;
RT   "Differential expression of genes encoding subthreshold-operating voltage-
RT   gated K+ channels in brain.";
RL   J. Neurosci. 21:4609-4624(2001).
CC   -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium
CC       channel. Elicits a slowly activating, rectifying current. Channel
CC       properties may be modulated by cAMP and subunit assembly.
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. Heteromultimer with KCNH2/ERG1
CC       and KCNH7/ERG3.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Highly expressed in celiac and superior mesenteric
CC       ganglia, but not detected in brain or in heart. Detected at low levels
CC       in retina. Also found in pituitary. Also found in the olfactory bulb
CC       (granular and mitral cell layers) (PubMed:11425889).
CC       {ECO:0000269|PubMed:10718922, ECO:0000269|PubMed:11425889}.
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   -!- SIMILARITY: Belongs to the potassium channel family. H (Eag)
CC       (TC 1.A.1.20) subfamily. Kv11.2/KCNH6 sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF016192; AAB94742.1; -; mRNA.
DR   RefSeq; NP_446389.1; NM_053937.1.
DR   AlphaFoldDB; O54853; -.
DR   BMRB; O54853; -.
DR   SMR; O54853; -.
DR   STRING; 10116.ENSRNOP00000010816; -.
DR   GuidetoPHARMACOLOGY; 573; -.
DR   TCDB; 1.A.1.20.2; the voltage-gated ion channel (vic) superfamily.
DR   PhosphoSitePlus; O54853; -.
DR   PaxDb; 10116-ENSRNOP00000010816; -.
DR   Ensembl; ENSRNOT00055051091; ENSRNOP00055042089; ENSRNOG00055029484.
DR   Ensembl; ENSRNOT00060023554; ENSRNOP00060018710; ENSRNOG00060013787.
DR   GeneID; 116745; -.
DR   KEGG; rno:116745; -.
DR   UCSC; RGD:620304; rat.
DR   AGR; RGD:620304; -.
DR   CTD; 81033; -.
DR   RGD; 620304; Kcnh6.
DR   eggNOG; KOG0498; Eukaryota.
DR   InParanoid; O54853; -.
DR   OrthoDB; 66005at2759; -.
DR   PhylomeDB; O54853; -.
DR   Reactome; R-RNO-1296072; Voltage gated Potassium channels.
DR   PRO; PR:O54853; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:RGD.
DR   GO; GO:0005267; F:potassium channel activity; TAS:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:RGD.
DR   GO; GO:0086011; P:membrane repolarization during action potential; IBA:GO_Central.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR   GO; GO:0086091; P:regulation of heart rate by cardiac conduction; 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; 1.10.1200.260; -; 1.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 1.
DR   Gene3D; 3.30.450.20; PAS domain; 1.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
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; IPR000014; PAS.
DR   InterPro; IPR035965; PAS-like_dom_sf.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   NCBIfam; TIGR00229; sensory_box; 1.
DR   PANTHER; PTHR10217:SF468; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 6; 1.
DR   PANTHER; PTHR10217; VOLTAGE AND LIGAND GATED POTASSIUM CHANNEL; 1.
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   SUPFAM; SSF51206; cAMP-binding domain-like; 1.
DR   SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 1.
PE   1: Evidence at protein level;
KW   Ion channel; Ion transport; Membrane; Potassium; Potassium channel;
KW   Potassium transport; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..950
FT                   /note="Potassium voltage-gated channel subfamily H member
FT                   6"
FT                   /id="PRO_0000054014"
FT   TOPO_DOM        1..261
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        262..282
FT                   /note="Helical; Name=Segment S1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        283..298
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        299..319
FT                   /note="Helical; Name=Segment S2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        320..340
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        341..361
FT                   /note="Helical; Name=Segment S3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        362..370
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        371..391
FT                   /note="Helical; Voltage-sensor; Name=Segment S4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        392..398
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        399..419
FT                   /note="Helical; Name=Segment S5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        420..463
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        464..484
FT                   /note="Pore-forming; Name=Segment H5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        485..490
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        491..511
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        512..950
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          41..70
FT                   /note="PAS"
FT   DOMAIN          92..144
FT                   /note="PAC"
FT   REGION          154..174
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          719..750
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          890..950
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           476..481
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   BINDING         594..711
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT   MUTAGEN         480
FT                   /note="G->S: Dominant negative mutant; abolishes ERG
FT                   current."
FT                   /evidence="ECO:0000269|PubMed:11212207"
SQ   SEQUENCE   950 AA;  105706 MW;  AB5AE674B08776F0 CRC64;
     MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM
     QRPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG
     AVIMFILNFE DLAQLLAKSS SRSLTQRLLS HSFLGSEGSH SRPSGQGPGP GRGKYRTVSQ
     IPQFTLNFVE FNLEKHRSGS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ
     APRIHRGTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESQR GTCGYTCSPL
     TVVDLIVDIM FVVDIVINFR TTYVNTNDEV VSHPRRIAVH YFKGWFLIDM VAAIPFDLLI
     FRTGSDETTT LIGLLKTARL LRLVRVARKL DRYSEYGAAV LFLLMCTFAL IAHWLACIWY
     AIGNVERPYL EPKIGWLDSL GAQLGKQYNG SDPASGPSVQ DKYVTALYFT FSSLTSVGFG
     NVSPNTNSEK VFSICVMLIG SLMYASIFGN VSAIIQRLYS GTARYHTQML RVKEFIRFHQ
     IPNPLRQRLE EYFQHAWSYT NGIDMNAVLK GFPECLQADI CLHLHRALLQ HCPAFRGASK
     GCLRALAVKF KTTHAPPGDT LVHLGDVLST LYFISRGSIE ILRDDVVVAI LGKNDIFGEP
     ASLHARPGKS SADVRALTYC DLHKIHRADL LEVLDMYPAF ADTFWNKLEV TFNLRDADGG
     LQSTPRQAPG HQDPQGFFLN DSQSGAAPSL SISDTSALWP ELLQQMPPSP PNPRQDLDCW
     HRELGFKLEQ LQAQMNRLES RVSSDLSRIL QLLQHPQGRP SYILGASASS DLASFPETSV
     TRSSESTLLV GHVPSAQTLS YGDLDDHIQT PRNFSPRTPH VAMAMDKTLV PSSEQEQPGG
     LLSPLASPLR PLEVPGLGGS RFPSLPEHLS SVPKQLEFQR HGSDPGFTRS
//