KCNN4_HUMAN
ID KCNN4_HUMAN Reviewed; 427 AA.
AC O15554; Q53XR4;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Intermediate conductance calcium-activated potassium channel protein 4;
DE Short=SK4;
DE Short=SKCa 4;
DE Short=SKCa4;
DE AltName: Full=IKCa1;
DE Short=IK1;
DE AltName: Full=KCa3.1;
DE AltName: Full=KCa4;
DE AltName: Full=Putative Gardos channel;
GN Name=KCNN4; Synonyms=IK1, IKCA1, KCA4, SK4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=9380751; DOI=10.1073/pnas.94.20.11013;
RA Joiner W.J., Wang L.-Y., Tang M.D., Kaczmarek L.K.;
RT "hSK4, a member of a novel subfamily of calcium-activated potassium
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11013-11018(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas;
RX PubMed=9326665; DOI=10.1073/pnas.94.21.11651;
RA Ishii T.M., Silvia C., Hirschberg B., Bond C.T., Adelman J.P., Maylie J.;
RT "A human intermediate conductance calcium-activated potassium channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11651-11656(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymph node;
RX PubMed=9407042; DOI=10.1074/jbc.272.52.32723;
RA Logsdon N.J., Kang J., Togo J.A., Christian E.P., Aiyar J.;
RT "A novel gene, hKCa4, encodes the calcium-activated potassium channel in
RT human T lymphocytes.";
RL J. Biol. Chem. 272:32723-32726(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9693050; DOI=10.1006/geno.1998.5333;
RA Ghanshani S., Coleman M., Gustavsson P., Wu A.C., Gargus J.J., Gutman G.A.,
RA Dahl N., Mohrenweiser H., Chandy K.G.;
RT "Human calcium-activated potassium channel gene KCNN4 maps to chromosome
RT 19q13.2 in the region deleted in diamond-blackfan anemia.";
RL Genomics 51:160-161(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10961988; DOI=10.1074/jbc.m003941200;
RA Ghanshani S., Wulff H., Miller M.J., Rohm H., Neben A., Gutman G.A.,
RA Cahalan M.D., Chandy K.G.;
RT "Up-regulation of the IKCa1 potassium channel during T-cell activation.
RT Molecular mechanism and functional consequences.";
RL J. Biol. Chem. 275:37137-37149(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Myometrium;
RA Mazzone J.N., Kaiser R.A., Buxton I.L.O.;
RT "Characterization of calcium-activated potassium channels in human
RT myometrium.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 227-367.
RA Golding S., Culliford S.J., Ellory J.C.;
RT "hIK1 (putative Gardos channel) PCR product amplified from the K562 human
RT erythroleukemic cell line.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP INTERACTION WITH CALMODULIN.
RX PubMed=10026195; DOI=10.1074/jbc.274.9.5746;
RA Fanger C.M., Ghanshani S., Logsdon N.J., Rauer H., Kalman K., Zhou J.,
RA Beckingham K., Chandy K.G., Cahalan M.D., Aiyar J.;
RT "Calmodulin mediates calcium-dependent activation of the intermediate
RT conductance KCa channel, IKCa1.";
RL J. Biol. Chem. 274:5746-5754(1999).
RN [12]
RP MUTAGENESIS OF THR-250 AND VAL-275.
RX PubMed=11425865; DOI=10.1074/jbc.m105231200;
RA Wulff H., Gutman G.A., Cahalan M.D., Chandy K.G.;
RT "Delineation of the clotrimazole/TRAM-34 binding site on the intermediate
RT conductance calcium-activated potassium channel, IKCa1.";
RL J. Biol. Chem. 276:32040-32045(2001).
RN [13]
RP INTERACTION WITH MTMR6.
RX PubMed=15831468; DOI=10.1128/mcb.25.9.3630-3638.2005;
RA Srivastava S., Li Z., Lin L., Liu G., Ko K., Coetzee W.A., Skolnik E.Y.;
RT "The phosphatidylinositol 3-phosphate phosphatase myotubularin-related
RT protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel
RT KCa3.1.";
RL Mol. Cell. Biol. 25:3630-3638(2005).
RN [14]
RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT HIS-358.
RX PubMed=17157250; DOI=10.1016/j.molcel.2006.11.012;
RA Srivastava S., Li Z., Ko K., Choudhury P., Albaqumi M., Johnson A.K.,
RA Yan Y., Backer J.M., Unutmaz D., Coetzee W.A., Skolnik E.Y.;
RT "Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside
RT diphosphate kinase B is required for activation of KCa3.1 and CD4 T
RT cells.";
RL Mol. Cell 24:665-675(2006).
RN [15]
RP FUNCTION, ACTIVITY REGULATION, AND DEPHOSPHORYLATION BY PTHP1.
RX PubMed=18796614; DOI=10.1073/pnas.0803678105;
RA Srivastava S., Zhdanova O., Di L., Li Z., Albaqumi M., Wulff H.,
RA Skolnik E.Y.;
RT "Protein histidine phosphatase 1 negatively regulates CD4 T cells by
RT inhibiting the K+ channel KCa3.1.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:14442-14446(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP FUNCTION.
RX PubMed=24591580; DOI=10.1073/pnas.1311029111;
RA Maekawa M., Terasaka S., Mochizuki Y., Kawai K., Ikeda Y., Araki N.,
RA Skolnik E.Y., Taguchi T., Arai H.;
RT "Sequential breakdown of 3-phosphorylated phosphoinositides is essential
RT for the completion of macropinocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E978-E987(2014).
RN [18]
RP VARIANTS DHS2 MET-282 AND HIS-352.
RX PubMed=26178367; DOI=10.1002/ajh.24117;
RA Andolfo I., Russo R., Manna F., Shmukler B.E., Gambale A., Vitiello G.,
RA De Rosa G., Brugnara C., Alper S.L., Snyder L.M., Iolascon A.;
RT "Novel Gardos channel mutations linked to dehydrated hereditary
RT stomatocytosis (xerocytosis).";
RL Am. J. Hematol. 90:921-926(2015).
RN [19]
RP INVOLVEMENT IN DHS2, VARIANT DHS2 HIS-352, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=26148990; DOI=10.1182/blood-2015-04-642496;
RA Rapetti-Mauss R., Lacoste C., Picard V., Guitton C., Lombard E.,
RA Loosveld M., Nivaggioni V., Dasilva N., Salgado D., Desvignes J.P.,
RA Beroud C., Viout P., Bernard M., Soriani O., Vinti H., Lacroze V.,
RA Feneant-Thibault M., Thuret I., Guizouarn H., Badens C.;
RT "A mutation in the Gardos channel is associated with hereditary
RT xerocytosis.";
RL Blood 126:1273-1280(2015).
RN [20]
RP VARIANTS DHS2 GLU-282 AND MET-282.
RX PubMed=26198474; DOI=10.1182/blood-2015-07-657957;
RA Glogowska E., Lezon-Geyda K., Maksimova Y., Schulz V.P., Gallagher P.G.;
RT "Mutations in the Gardos channel (KCNN4) are associated with hereditary
RT xerocytosis.";
RL Blood 126:1281-1284(2015).
CC -!- FUNCTION: Forms a voltage-independent potassium channel that is
CC activated by intracellular calcium (PubMed:26148990). Activation is
CC followed by membrane hyperpolarization which promotes calcium influx.
CC Required for maximal calcium influx and proliferation during the
CC reactivation of naive T-cells (PubMed:17157250, PubMed:18796614). Plays
CC a role in the late stages of EGF-induced macropinocytosis
CC (PubMed:24591580). {ECO:0000269|PubMed:17157250,
CC ECO:0000269|PubMed:18796614, ECO:0000269|PubMed:24591580,
CC ECO:0000269|PubMed:26148990}.
CC -!- ACTIVITY REGULATION: The channel is inhibited by clotrimazole and
CC charybdotoxin but is insensitive to apamin.
CC {ECO:0000269|PubMed:17157250, ECO:0000269|PubMed:18796614}.
CC -!- SUBUNIT: Heterotetramer of potassium channel proteins (Probable).
CC Interacts with MTMR6. {ECO:0000269|PubMed:10026195,
CC ECO:0000269|PubMed:15831468, ECO:0000305}.
CC -!- INTERACTION:
CC O15554; Q13323: BIK; NbExp=3; IntAct=EBI-2924473, EBI-700794;
CC O15554; P62158: CALM3; NbExp=2; IntAct=EBI-2924473, EBI-397435;
CC O15554; P13569: CFTR; NbExp=5; IntAct=EBI-2924473, EBI-349854;
CC O15554; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-2924473, EBI-12208021;
CC O15554; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-2924473, EBI-12175685;
CC O15554; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-2924473, EBI-13345167;
CC O15554; Q9NRX4: PHPT1; NbExp=2; IntAct=EBI-2924473, EBI-740955;
CC O15554; Q01453: PMP22; NbExp=3; IntAct=EBI-2924473, EBI-2845982;
CC O15554; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-2924473, EBI-8644112;
CC O15554; P61266: STX1B; NbExp=3; IntAct=EBI-2924473, EBI-9071709;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26148990};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed in non-excitable tissues.
CC -!- INDUCTION: Up-regulated by phorbol myristate acetate (PMA) and
CC phytohemagglutinin (PHA) in T-cells.
CC -!- PTM: Phosphorylation at His-358 by NDKB activates the channel, and
CC conversely it's dephosphorylation by PHPT1 inhibits the channel.
CC {ECO:0000269|PubMed:17157250}.
CC -!- DISEASE: Dehydrated hereditary stomatocytosis 2 (DHS2) [MIM:616689]: An
CC autosomal dominant hemolytic anemia characterized by primary
CC erythrocyte dehydration. Erythrocytes exhibit decreased total cation
CC and potassium content that are not accompanied by a proportional net
CC gain of sodium and water. Affected individuals typically manifest mild
CC to moderate compensated hemolytic anemia, with an increased erythrocyte
CC mean corpuscular hemoglobin concentration and a decreased osmotic
CC fragility, both of which reflect cellular dehydration. Their red cells
CC exhibit a panel of various shape abnormalities such as elliptocytes,
CC hemighosts, schizocytes, and very rare stomatocytic cells.
CC Complications such as splenomegaly and cholelithiasis, resulting from
CC increased red cell trapping in the spleen and elevated bilirubin
CC levels, respectively, may occur. {ECO:0000269|PubMed:26148990,
CC ECO:0000269|PubMed:26178367, ECO:0000269|PubMed:26198474}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the potassium channel KCNN family. KCa3.1/KCNN4
CC subfamily. {ECO:0000305}.
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DR EMBL; AF000972; AAB82739.1; -; mRNA.
DR EMBL; AF022150; AAC23541.1; -; mRNA.
DR EMBL; AF022797; AAC51913.1; -; mRNA.
DR EMBL; AF033021; AAC36804.1; -; mRNA.
DR EMBL; AF305735; AAG26917.1; -; Genomic_DNA.
DR EMBL; AF305731; AAG26917.1; JOINED; Genomic_DNA.
DR EMBL; AF305732; AAG26917.1; JOINED; Genomic_DNA.
DR EMBL; AF305733; AAG26917.1; JOINED; Genomic_DNA.
DR EMBL; AF305734; AAG26917.1; JOINED; Genomic_DNA.
DR EMBL; AF395661; AAK81862.1; -; mRNA.
DR EMBL; BT007426; AAP36094.1; -; mRNA.
DR EMBL; CH471126; EAW57230.1; -; Genomic_DNA.
DR EMBL; BC015337; AAH15337.1; -; mRNA.
DR EMBL; AF053403; AAC35281.1; -; mRNA.
DR CCDS; CCDS12630.1; -.
DR RefSeq; NP_002241.1; NM_002250.2.
DR PDB; 6CNM; EM; 3.40 A; A/B/C/D=1-427.
DR PDB; 6CNN; EM; 3.50 A; A/B/C/D=1-427.
DR PDB; 6CNO; EM; 4.70 A; A/B/C/D=1-427.
DR PDB; 6D42; X-ray; 1.75 A; A/B=376-415.
DR PDBsum; 6CNM; -.
DR PDBsum; 6CNN; -.
DR PDBsum; 6CNO; -.
DR PDBsum; 6D42; -.
DR AlphaFoldDB; O15554; -.
DR SMR; O15554; -.
DR BioGRID; 109984; 104.
DR DIP; DIP-48598N; -.
DR IntAct; O15554; 14.
DR MINT; O15554; -.
DR STRING; 9606.ENSP00000262888; -.
DR BindingDB; O15554; -.
DR ChEMBL; CHEMBL4305; -.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB00468; Quinine.
DR DrugBank; DB09089; Trimebutine.
DR DrugCentral; O15554; -.
DR GuidetoPHARMACOLOGY; 384; -.
DR TCDB; 1.A.1.16.2; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; O15554; -.
DR PhosphoSitePlus; O15554; -.
DR SwissPalm; O15554; -.
DR BioMuta; KCNN4; -.
DR EPD; O15554; -.
DR jPOST; O15554; -.
DR MassIVE; O15554; -.
DR MaxQB; O15554; -.
DR PaxDb; O15554; -.
DR PeptideAtlas; O15554; -.
DR PRIDE; O15554; -.
DR ProteomicsDB; 48757; -.
DR Antibodypedia; 31124; 311 antibodies from 33 providers.
DR DNASU; 3783; -.
DR Ensembl; ENST00000648319.1; ENSP00000496939.1; ENSG00000104783.15.
DR GeneID; 3783; -.
DR KEGG; hsa:3783; -.
DR MANE-Select; ENST00000648319.1; ENSP00000496939.1; NM_002250.3; NP_002241.1.
DR UCSC; uc002oxl.3; human.
DR CTD; 3783; -.
DR DisGeNET; 3783; -.
DR GeneCards; KCNN4; -.
DR HGNC; HGNC:6293; KCNN4.
DR HPA; ENSG00000104783; Tissue enhanced (salivary).
DR MalaCards; KCNN4; -.
DR MIM; 602754; gene.
DR MIM; 616689; phenotype.
DR neXtProt; NX_O15554; -.
DR OpenTargets; ENSG00000104783; -.
DR Orphanet; 586; Cystic fibrosis.
DR Orphanet; 3202; Dehydrated hereditary stomatocytosis.
DR PharmGKB; PA222; -.
DR VEuPathDB; HostDB:ENSG00000104783; -.
DR eggNOG; KOG3684; Eukaryota.
DR GeneTree; ENSGT00950000182904; -.
DR HOGENOM; CLU_014617_5_2_1; -.
DR InParanoid; O15554; -.
DR OMA; PPCVQDL; -.
DR OrthoDB; 907751at2759; -.
DR PhylomeDB; O15554; -.
DR TreeFam; TF315015; -.
DR PathwayCommons; O15554; -.
DR Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR SignaLink; O15554; -.
DR SIGNOR; O15554; -.
DR BioGRID-ORCS; 3783; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; KCNN4; human.
DR GeneWiki; KCNN4; -.
DR GenomeRNAi; 3783; -.
DR Pharos; O15554; Tchem.
DR PRO; PR:O15554; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O15554; protein.
DR Bgee; ENSG00000104783; Expressed in olfactory segment of nasal mucosa and 137 other tissues.
DR ExpressionAtlas; O15554; baseline and differential.
DR Genevisible; O15554; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:BHF-UCL.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0022894; F:Intermediate conductance calcium-activated potassium channel activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; TAS:Reactome.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:BHF-UCL.
DR GO; GO:0016286; F:small conductance calcium-activated potassium channel activity; IEA:InterPro.
DR GO; GO:0006816; P:calcium ion transport; IDA:BHF-UCL.
DR GO; GO:0006884; P:cell volume homeostasis; IEA:Ensembl.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; IBA:GO_Central.
DR GO; GO:0045332; P:phospholipid translocation; IEA:Ensembl.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; TAS:Reactome.
DR GO; GO:0050714; P:positive regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0046541; P:saliva secretion; IEA:Ensembl.
DR GO; GO:0030322; P:stabilization of membrane potential; IDA:BHF-UCL.
DR InterPro; IPR004178; CaM-bd_dom.
DR InterPro; IPR036122; CaM-bd_dom_sf.
DR InterPro; IPR015449; K_chnl_Ca-activ_SK.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR10153; PTHR10153; 1.
DR Pfam; PF02888; CaMBD; 1.
DR Pfam; PF07885; Ion_trans_2; 1.
DR Pfam; PF03530; SK_channel; 1.
DR SMART; SM01053; CaMBD; 1.
DR SUPFAM; SSF81327; SSF81327; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calmodulin-binding; Cell membrane; Disease variant;
KW Hereditary hemolytic anemia; Immunity; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..427
FT /note="Intermediate conductance calcium-activated potassium
FT channel protein 4"
FT /id="PRO_0000155017"
FT TRANSMEM 29..49
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..79
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT INTRAMEM 241..261
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT REGION 286..347
FT /note="Calmodulin-binding"
FT MOD_RES 358
FT /note="Phosphohistidine"
FT /evidence="ECO:0000269|PubMed:17157250"
FT VARIANT 282
FT /note="V -> E (in DHS2; dbSNP:rs1057519077)"
FT /evidence="ECO:0000269|PubMed:26198474"
FT /id="VAR_074485"
FT VARIANT 282
FT /note="V -> M (in DHS2; dbSNP:rs1057519076)"
FT /evidence="ECO:0000269|PubMed:26178367,
FT ECO:0000269|PubMed:26198474"
FT /id="VAR_074486"
FT VARIANT 352
FT /note="R -> H (in DHS2; no effect on plasma membrane
FT localization; increases calcium-activated potassium channel
FT activity; dbSNP:rs774455945)"
FT /evidence="ECO:0000269|PubMed:26148990,
FT ECO:0000269|PubMed:26178367"
FT /id="VAR_074487"
FT MUTAGEN 250
FT /note="T->S: Loss of sensitivity to triarylmethanes."
FT /evidence="ECO:0000269|PubMed:11425865"
FT MUTAGEN 275
FT /note="V->A: Loss of sensitivity to triarylmethanes."
FT /evidence="ECO:0000269|PubMed:11425865"
FT CONFLICT 66
FT /note="S -> G (in Ref. 6; AAK81862)"
FT /evidence="ECO:0000305"
FT HELIX 12..50
FT /evidence="ECO:0007829|PDB:6CNM"
FT TURN 51..56
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 57..91
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 149..154
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 155..161
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 162..170
FT /evidence="ECO:0007829|PDB:6CNM"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 177..186
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 192..202
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 204..226
FT /evidence="ECO:0007829|PDB:6CNM"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 237..248
FT /evidence="ECO:0007829|PDB:6CNM"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:6CNN"
FT HELIX 261..287
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 293..330
FT /evidence="ECO:0007829|PDB:6CNM"
FT TURN 335..337
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 338..368
FT /evidence="ECO:0007829|PDB:6CNM"
FT HELIX 378..413
FT /evidence="ECO:0007829|PDB:6D42"
SQ SEQUENCE 427 AA; 47696 MW; 23F9AF66609B410F CRC64;
MGGDLVLGLG ALRRRKRLLE QEKSLAGWAL VLAGTGIGLM VLHAEMLWFG GCSWALYLFL
VKCTISISTF LLLCLIVAFH AKEVQLFMTD NGLRDWRVAL TGRQAAQIVL ELVVCGLHPA
PVRGPPCVQD LGAPLTSPQP WPGFLGQGEA LLSLAMLLRL YLVPRAVLLR SGVLLNASYR
SIGALNQVRF RHWFVAKLYM NTHPGRLLLG LTLGLWLTTA WVLSVAERQA VNATGHLSDT
LWLIPITFLT IGYGDVVPGT MWGKIVCLCT GVMGVCCTAL LVAVVARKLE FNKAEKHVHN
FMMDIQYTKE MKESAARVLQ EAWMFYKHTR RKESHAARRH QRKLLAAINA FRQVRLKHRK
LREQVNSMVD ISKMHMILYD LQQNLSSSHR ALEKQIDTLA GKLDALTELL STALGPRQLP
EPSQQSK
