ID KCNH1_MOUSE Reviewed; 989 AA. AC Q60603; Q32MR6; Q3USQ9; DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2016, sequence version 2. DT 24-JAN-2024, entry version 203. DE RecName: Full=Potassium voltage-gated channel subfamily H member 1; DE AltName: Full=Ether-a-go-go potassium channel 1; DE Short=EAG channel 1; DE Short=EAG1; DE Short=m-eag; DE AltName: Full=Voltage-gated potassium channel subunit Kv10.1; GN Name=Kcnh1; Synonyms=Eag; 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 [MRNA]. RC TISSUE=Brain; RX PubMed=8159766; DOI=10.1073/pnas.91.8.3438; RA Warmke J.W., Ganetzky B.; RT "A family of potassium channel genes related to eag in Drosophila and RT mammals."; RL Proc. Natl. Acad. Sci. U.S.A. 91:3438-3442(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE24272.1}; RC TISSUE=Corpora quadrigemina {ECO:0000312|EMBL:BAE24272.1}; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP ACTIVITY REGULATION, LACK OF CYCLIC NUCLEOTIDE BINDING, FUNCTION, RP SUBCELLULAR LOCATION, AND DOMAIN. RX PubMed=19671703; DOI=10.1074/jbc.m109.016337; RA Brelidze T.I., Carlson A.E., Zagotta W.N.; RT "Absence of direct cyclic nucleotide modulation of mEAG1 and hERG1 channels RT revealed with fluorescence and electrophysiological methods."; RL J. Biol. Chem. 284:27989-27997(2009). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-974; SER-978 AND SER-981, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; 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 [7] RP INTERACTION WITH RABEP1. RX PubMed=22841712; DOI=10.1016/j.febslet.2012.07.055; RA Ninkovic M., Mitkovski M., Kohl T., Stuhmer W., Pardo L.A.; RT "Physical and functional interaction of KV10.1 with Rabaptin-5 impacts ion RT channel trafficking."; RL FEBS Lett. 586:3077-3084(2012). RN [8] RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=23424202; DOI=10.1093/hmg/ddt076; RA Ufartes R., Schneider T., Mortensen L.S., de Juan Romero C., Hentrich K., RA Knoetgen H., Beilinson V., Moebius W., Tarabykin V., Alves F., Pardo L.A., RA Rawlins J.N., Stuehmer W.; RT "Behavioural and functional characterization of Kv10.1 (Eag1) knockout RT mice."; RL Hum. Mol. Genet. 22:2247-2262(2013). RN [9] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=25556795; DOI=10.1113/jphysiol.2014.281600; RA Mortensen L.S., Schmidt H., Farsi Z., Barrantes-Freer A., Rubio M.E., RA Ufartes R., Eilers J., Sakaba T., Stuehmer W., Pardo L.A.; RT "KV 10.1 opposes activity-dependent increase in Ca2+ influx into the RT presynaptic terminal of the parallel fibre-Purkinje cell synapse."; RL J. Physiol. (Lond.) 593:181-196(2015). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 552-707, DOMAIN, RP CALMODULIN-BINDING REGION, AND MUTAGENESIS OF VAL-628; 697-LEU--TYR-699; RP TYR-699; 699-TYR--LEU-701 AND 705-ILE--PHE-707. RX PubMed=22732247; DOI=10.1016/j.jmb.2012.06.025; RA Marques-Carvalho M.J., Sahoo N., Muskett F.W., Vieira-Pires R.S., RA Gabant G., Cadene M., Schonherr R., Morais-Cabral J.H.; RT "Structural, biochemical, and functional characterization of the cyclic RT nucleotide binding homology domain from the mouse EAG1 potassium channel."; RL J. Mol. Biol. 423:34-46(2012). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-136 AND 552-724, FUNCTION, RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 7-ARG-ARG-8; ARG-57; RP GLU-627 AND ASP-642. RX PubMed=23975098; DOI=10.1038/nature12487; RA Haitin Y., Carlson A.E., Zagotta W.N.; RT "The structural mechanism of KCNH-channel regulation by the eag domain."; RL Nature 501:444-448(2013). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 28-137. RX PubMed=23555008; DOI=10.1371/journal.pone.0059265; RA Adaixo R., Harley C.A., Castro-Rodrigues A.F., Morais-Cabral J.H.; RT "Structural properties of PAS domains from the KCNH potassium channels."; RL PLoS ONE 8:E59265-E59265(2013). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 727-743 IN COMPLEX WITH CALM, RP MUTAGENESIS OF VAL-737; LEU-740 AND PHE-741, AND INTERACTION WITH CALM. RX PubMed=27618660; DOI=10.1016/j.str.2016.07.020; RA Marques-Carvalho M.J., Oppermann J., Munoz E., Fernandes A.S., Gabant G., RA Cadene M., Heinemann S.H., Schoenherr R., Morais-Cabral J.H.; RT "Molecular insights into the mechanism of calmodulin inhibition of the EAG1 RT potassium channel."; RL Structure 24:1742-1754(2016). CC -!- FUNCTION: Pore-forming (alpha) subunit of a voltage-gated delayed CC rectifier potassium channel (PubMed:19671703, PubMed:23975098). Channel CC properties are modulated by subunit assembly. Mediates IK(NI) current CC in myoblasts. Involved in the regulation of cell proliferation and CC differentiation, in particular adipogenic and osteogenic CC differentiation in bone marrow-derived mesenchymal stem cells (MSCs) CC (By similarity). {ECO:0000250|UniProtKB:O95259, CC ECO:0000269|PubMed:19671703, ECO:0000269|PubMed:23975098}. CC -!- ACTIVITY REGULATION: Channel activity is inhibited by interaction with CC Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha CC subunit with a calmodulin chain is sufficient to promote channel CC closure (By similarity). Channel activity is not regulated by cyclic CC nucleotides (PubMed:19671703). Channel activity is inhibited by binding CC intracellular phosphatidylinositol-3,5-bisphosphate and CC phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by CC phosphatidylinositol 4-phosphate (By similarity). CC {ECO:0000250|UniProtKB:O95259, ECO:0000269|PubMed:19671703}. CC -!- SUBUNIT: The potassium channel is composed of a homo- or CC heterotetrameric complex of pore-forming alpha subunits that can CC associate with modulating beta subunits. Heteromultimer with KCNH5/EAG2 CC (By similarity). Interacts with ALG10B (By similarity). Interacts with CC RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN. CC Interacts (via C-terminal cytoplasmic region) with Ca(2+)-bound CC calmodulin (PubMed:27618660). {ECO:0000250|UniProtKB:O95259, CC ECO:0000269|PubMed:22841712, ECO:0000269|PubMed:27618660}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19671703, CC ECO:0000269|PubMed:23975098}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:O95259}. Nucleus inner membrane CC {ECO:0000250|UniProtKB:O95259}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:O95259}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:Q63472}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q63472}. Presynaptic cell membrane CC {ECO:0000269|PubMed:25556795}. Perikaryon CC {ECO:0000250|UniProtKB:Q63472}. Postsynaptic density membrane CC {ECO:0000250|UniProtKB:Q63472}. Early endosome membrane CC {ECO:0000250|UniProtKB:O95259}. Note=Perinuclear KCNH1 is located to CC NPC-free islands. {ECO:0000250|UniProtKB:O95259}. CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level) CC (PubMed:23424202, PubMed:25556795). Highly expressed in olfactory bulb. CC Detected in brain cortex, hippocampus, brain stem, striatum, thalamus, CC hypothalamus and spinal cord (PubMed:23424202). CC {ECO:0000269|PubMed:23424202, ECO:0000269|PubMed:25556795}. 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. {ECO:0000250|UniProtKB:Q63472}. CC -!- DOMAIN: The C-terminal region interacts with the cyclic nucleotide- CC binding domain and contributes to regulate channel gating. CC {ECO:0000269|PubMed:23975098, ECO:0000305|PubMed:22732247}. CC -!- DOMAIN: The PAS and PAC domain interact with the cyclic nucleotide- CC binding domain and contribute to the regulation of channel gating CC (PubMed:23975098). Calmodulin binding clamps together the PAS and PAC CC domain with the cyclic nucleotide-binding domain from a neighboring CC subunit and causes a conformation change that leads to channel closure. CC {ECO:0000250|UniProtKB:Q63472, ECO:0000269|PubMed:23975098}. CC -!- DOMAIN: The cyclic nucleotide-binding domain lacks residues that are CC essential for nucleotide-binding and cannot bind cyclic nucleotides CC (PubMed:19671703). Instead, residues from the C-terminal domain (the CC so-called intrinsic ligand) bind in the cavity that would be expected CC to bind cyclic nucleotides. Interaction with the C-terminal region CC hinders interaction with CALM and reduces the affinity for CALM. CC {ECO:0000269|PubMed:19671703, ECO:0000269|PubMed:22732247, CC ECO:0000269|PubMed:23975098}. CC -!- PTM: Channel activity is regulated via tyrosine CC phosphorylation/dephosphorylation by SRC and PTPN6. CC {ECO:0000250|UniProtKB:O95259}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are viable and CC fertile, and have normal brain morphology. Likewise, there is no change CC in the electrophysiological properties of cerebellar Purkinje cells and CC in the shape and frequency of action potentials. CC {ECO:0000269|PubMed:23424202}. CC -!- SIMILARITY: Belongs to the potassium channel family. H (Eag) CC (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U04294; AAA62474.1; -; mRNA. DR EMBL; AK140193; BAE24272.1; -; mRNA. DR EMBL; CH466555; EDL12967.1; -; Genomic_DNA. DR EMBL; BC109013; AAI09014.1; -; mRNA. DR CCDS; CCDS15627.1; -. DR PIR; I48912; I48912. DR RefSeq; NP_034730.1; NM_010600.3. DR PDB; 4F8A; X-ray; 2.20 A; A=552-707. DR PDB; 4HOI; X-ray; 1.85 A; A/B/C/D=28-137. DR PDB; 4LLO; X-ray; 2.00 A; A/C/E/G=552-724, B/D/F/H=6-136. DR PDB; 5HIT; X-ray; 2.85 A; B=727-743. DR PDBsum; 4F8A; -. DR PDBsum; 4HOI; -. DR PDBsum; 4LLO; -. DR PDBsum; 5HIT; -. DR AlphaFoldDB; Q60603; -. DR SMR; Q60603; -. DR BioGRID; 200892; 4. DR IntAct; Q60603; 1. DR MINT; Q60603; -. DR STRING; 10090.ENSMUSP00000077563; -. DR GlyCosmos; Q60603; 2 sites, No reported glycans. DR GlyGen; Q60603; 5 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q60603; -. DR PhosphoSitePlus; Q60603; -. DR PaxDb; 10090-ENSMUSP00000077563; -. DR ProteomicsDB; 269200; -. DR DNASU; 16510; -. DR GeneID; 16510; -. DR KEGG; mmu:16510; -. DR UCSC; uc007edo.2; mouse. DR AGR; MGI:1341721; -. DR CTD; 3756; -. DR MGI; MGI:1341721; Kcnh1. DR eggNOG; KOG0501; Eukaryota. DR InParanoid; Q60603; -. DR OrthoDB; 66005at2759; -. DR PhylomeDB; Q60603; -. DR TreeFam; TF313130; -. DR Reactome; R-MMU-1296072; Voltage gated Potassium channels. DR BioGRID-ORCS; 16510; 4 hits in 76 CRISPR screens. DR ChiTaRS; Kcnh1; mouse. DR PRO; PR:Q60603; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q60603; Protein. DR GO; GO:0030673; C:axolemma; ISO:MGI. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005637; C:nuclear inner membrane; ISO:MGI. DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell. DR GO; GO:0034705; C:potassium channel complex; ISO:MGI. DR GO; GO:0042734; C:presynaptic membrane; ISO:MGI. DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB. DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI. DR GO; GO:0005516; F:calmodulin binding; ISO:MGI. DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:1902936; F:phosphatidylinositol bisphosphate binding; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI. DR GO; GO:0099508; F:voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IDA:SynGO. DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; ISO:MGI. DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central. DR GO; GO:0099509; P:regulation of presynaptic cytosolic calcium ion concentration; IDA:SynGO. DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO. DR GO; GO:0001964; P:startle response; ISO:MGI. 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; IPR003949; K_chnl_volt-dep_EAG. DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/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 NCBIfam; TIGR00229; sensory_box; 1. DR PANTHER; PTHR10217:SF530; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 1; 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; PR01464; EAGCHANNEL. DR SMART; SM00100; cNMP; 1. DR SMART; SM00086; PAC; 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. DR PROSITE; PS50113; PAC; 1. DR PROSITE; PS50112; PAS; 1. DR Genevisible; Q60603; MM. PE 1: Evidence at protein level; KW 3D-structure; Calmodulin-binding; Cell membrane; Cell projection; Endosome; KW Glycoprotein; Ion channel; Ion transport; Lipid-binding; Membrane; Nucleus; KW Phosphoprotein; Postsynaptic cell membrane; Potassium; Potassium channel; KW Potassium transport; Reference proteome; Synapse; Transmembrane; KW Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1..989 FT /note="Potassium voltage-gated channel subfamily H member FT 1" FT /id="PRO_0000053995" FT TOPO_DOM 1..220 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TRANSMEM 221..241 FT /note="Helical; Name=Segment S1" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 242..248 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TRANSMEM 249..269 FT /note="Helical; Name=Segment S2" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 270..290 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TRANSMEM 291..309 FT /note="Helical; Name=Segment S3" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 310..345 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TRANSMEM 346..368 FT /note="Helical; Voltage-sensor; Name=Segment S4" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 369..377 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TRANSMEM 378..399 FT /note="Helical; Name=Segment S5" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 400..448 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT INTRAMEM 449..470 FT /note="Pore-forming; Name=Segment H5" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 471..477 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TRANSMEM 478..498 FT /note="Helical; Name=Segment S6" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT TOPO_DOM 499..989 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT DOMAIN 14..94 FT /note="PAS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 93..145 FT /note="PAC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141" FT REGION 151..162 FT /note="Required for phosphatidylinositol bisphosphate FT binding" FT /evidence="ECO:0000250|UniProtKB:O95259" FT REGION 673..770 FT /note="Calmodulin-binding" FT /evidence="ECO:0000269|PubMed:22732247, FT ECO:0000269|PubMed:27618660" FT REGION 699..701 FT /note="Interaction with cyclic nucleotide-binding pocket" FT /evidence="ECO:0000269|PubMed:22732247" FT REGION 857..905 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 924..964 FT /note="CAD (involved in subunit assembly)" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT REGION 961..989 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 463..468 FT /note="Selectivity filter" FT /evidence="ECO:0000250|UniProtKB:Q63472" FT COMPBIAS 857..874 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 881..897 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 961..975 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 974 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 978 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 981 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CARBOHYD 415 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 433 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT MUTAGEN 7..8 FT /note="RR->AA,EE: Strongly shifts the voltage-dependent FT channel activation to more depolarized membrane FT potentials." FT /evidence="ECO:0000269|PubMed:23975098" FT MUTAGEN 57 FT /note="R->D: Decreases the rate of channel opening. No FT effect; when associated with R-642." FT /evidence="ECO:0000269|PubMed:23975098" FT MUTAGEN 627 FT /note="E->A,R: Strongly shifts the voltage-dependent FT channel activation to much more depolarized membrane FT potentials." FT /evidence="ECO:0000269|PubMed:23975098" FT MUTAGEN 628 FT /note="V->A,L: Mildly increases the affinity for CALM." FT /evidence="ECO:0000269|PubMed:22732247" FT MUTAGEN 642 FT /note="D->R: Decreases the rate of channel opening. No FT effect; when associated with D-57." FT /evidence="ECO:0000269|PubMed:23975098" FT MUTAGEN 697..699 FT /note="LTY->ATA: Increases the affinity for CALM." FT /evidence="ECO:0000269|PubMed:22732247" FT MUTAGEN 699..701 FT /note="YNL->ANA: Increases the affinity for CALM." FT /evidence="ECO:0000269|PubMed:22732247" FT MUTAGEN 699 FT /note="Y->W: Mildly increases the affinity for CALM." FT /evidence="ECO:0000269|PubMed:22732247" FT MUTAGEN 705..707 FT /note="IVF->AAA: Decreases the affinity for CALM." FT /evidence="ECO:0000269|PubMed:22732247" FT MUTAGEN 737 FT /note="V->A: No effect on affinity for CALM; when FT associated with A-740." FT /evidence="ECO:0000269|PubMed:27618660" FT MUTAGEN 737 FT /note="V->S: Decreases affinity for CALM 230-fold; when FT associated with S-740." FT /evidence="ECO:0000269|PubMed:27618660" FT MUTAGEN 740 FT /note="L->A: No effect on affinity for CALM; when FT associated with A-737." FT /evidence="ECO:0000269|PubMed:27618660" FT MUTAGEN 740 FT /note="L->S: Decreases affinity for CALM 230-fold; when FT associated with S-737." FT /evidence="ECO:0000269|PubMed:27618660" FT MUTAGEN 741 FT /note="F->S: Decreases affinity for CALM about 30-fold." FT /evidence="ECO:0000269|PubMed:27618660" FT CONFLICT 808 FT /note="V -> M (in Ref. 1; AAA62474 and 2; BAE24272)" FT HELIX 17..22 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 29..34 FT /evidence="ECO:0007829|PDB:4HOI" FT STRAND 41..45 FT /evidence="ECO:0007829|PDB:4HOI" FT HELIX 47..53 FT /evidence="ECO:0007829|PDB:4HOI" FT HELIX 57..60 FT /evidence="ECO:0007829|PDB:4HOI" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:4HOI" FT HELIX 77..88 FT /evidence="ECO:0007829|PDB:4HOI" FT STRAND 93..100 FT /evidence="ECO:0007829|PDB:4HOI" FT STRAND 106..117 FT /evidence="ECO:0007829|PDB:4HOI" FT STRAND 123..132 FT /evidence="ECO:0007829|PDB:4HOI" FT TURN 134..136 FT /evidence="ECO:0007829|PDB:4HOI" FT STRAND 555..559 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 565..571 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 573..576 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 580..582 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 587..596 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 598..602 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 607..609 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 613..615 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 617..624 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 626..630 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 633..638 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 643..645 FT /evidence="ECO:0007829|PDB:4LLO" FT TURN 647..651 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 658..673 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 674..683 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 685..694 FT /evidence="ECO:0007829|PDB:4LLO" FT STRAND 698..700 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 710..718 FT /evidence="ECO:0007829|PDB:4LLO" FT HELIX 736..741 FT /evidence="ECO:0007829|PDB:5HIT" SQ SEQUENCE 989 AA; 111282 MW; AEC4C730E253DDC1 CRC64; MTMAGGRRGL VAPQNTFLEN IVRRSNDTNF VLGNAQIVDW PIVYSNDGFC KLSGYHRAEV MQKSSACSFM YGELTDKDTV EKVRQTFENY EMNSFEILMY KKNRTPVWFF VKIAPIRNEQ DKVVLFLCTF SDITAFKQPI EDDSCKGWGK FARLTRALTS SRGVLQQLAP SVQKGENVHK HSRLAEVLQL GSDILPQYKQ EAPKTPPHII LHYCVFKTTW DWIILILTFY TAILVPYNVS FKTRQNNVAW LVVDSIVDVI FLVDIVLNFH TTFVGPAGEV ISDPKLIRMN YLKTWFVIDL LSCLPYDVIN AFENVDEVSA FMGDPGKIGF ADQIPPPLEG RESQGISSLF SSLKVVRLLR LGRVARKLDH YIEYGAAVLV LLVCVFGLAA HWMACIWYSI GDYEIFDEDT KTIRNNSWLY QLALDIGTPY QFNGSGSGKW EGGPSKNSVY ISSLYFTMTS LTSVGFGNIA PSTDIEKIFA VAIMMIGSLL YATIFGNVTT IFQQMYANTN RYHEMLNSVR DFLKLYQVPK GLSERVMDYI VSTWSMSRGI DTEKVLQICP KDMRADICVH LNRKVFKEHP AFRLASDGCL RALAMEFQTV HCAPGDLIYH AGESVDSLCF VVSGSLEVIQ DDEVVAILGK GDVFGDVFWK EATLAQSCAN VRALTYCDLH VIKRDALQKV LEFYTAFSHS FSRNLILTYN LRKRIVFRKI SDVKREEEER MKRKNEAPLI LPPDHPVRRL FQRFRQQKEA RLAAERGGRD LDDLDVEKGN ALTDHTSANH SLVKASVVTV RESPATPVSF QAATTSTVSD HAKLHAPGSE CLGPKAVSCD PAKRKGWARF KDACGKGEDW NKVSKAESME TLPERTKAPG EATLKKTDSC DSGITKSDLR LDNVGETRSP QDRSPILAEV KHSFYPIPEQ TLQATVLEVK YELKEDIKAL NAKMTSIEKQ LSEILRILMS RGSAQSPQET GEISRPQSPE SDRDIFGAS //