ANO1_MOUSE
ID ANO1_MOUSE Reviewed; 960 AA.
AC Q8BHY3; Q6P5C6; Q8BI26; Q99JK1;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Anoctamin-1;
DE AltName: Full=Transmembrane protein 16A;
GN Name=Ano1; Synonyms=Tmem16a;
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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP PORE-FORMING REGION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-621;
RP CYS-625; CYS-630; CYS-635; LYS-645 AND LYS-668.
RX PubMed=18724360; DOI=10.1038/nature07313;
RA Yang Y.D., Cho H., Koo J.Y., Tak M.H., Cho Y., Shim W.-S., Park S.P.,
RA Lee J., Lee B., Kim B.-M., Raouf R., Shin Y.K., Oh U.;
RT "TMEM16A confers receptor-activated calcium-dependent chloride
RT conductance.";
RL Nature 455:1210-1215(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head, Kidney, and Skin;
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 MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Eye, and Mammary tumor;
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18585372; DOI=10.1016/j.ydbio.2008.06.009;
RA Rock J.R., Futtner C.R., Harfe B.D.;
RT "The transmembrane protein TMEM16A is required for normal development of
RT the murine trachea.";
RL Dev. Biol. 321:141-149(2008).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=18729231; DOI=10.1002/dvdy.21676;
RA Rock J.R., Harfe B.D.;
RT "Expression of TMEM16 paralogs during murine embryogenesis.";
RL Dev. Dyn. 237:2566-2574(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, 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 [7]
RP TISSUE SPECIFICITY.
RX PubMed=20056604; DOI=10.1074/jbc.m109.065367;
RA Schreiber R., Uliyakina I., Kongsuphol P., Warth R., Mirza M.,
RA Martins J.R., Kunzelmann K.;
RT "Expression and function of epithelial anoctamins.";
RL J. Biol. Chem. 285:7838-7845(2010).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22075693; DOI=10.1152/ajpcell.00140.2011;
RA Duran C., Qu Z., Osunkoya A.O., Cui Y., Hartzell H.C.;
RT "ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular
RT proteins.";
RL Am. J. Physiol. 302:C482-C493(2012).
RN [9]
RP MUTAGENESIS OF LYS-588.
RX PubMed=23021219; DOI=10.1016/j.cell.2012.07.036;
RA Yang H., Kim A., David T., Palmer D., Jin T., Tien J., Huang F., Cheng T.,
RA Coughlin S.R., Jan Y.N., Jan L.Y.;
RT "TMEM16F forms a Ca(2+)-activated cation channel required for lipid
RT scrambling in platelets during blood coagulation.";
RL Cell 151:111-122(2012).
RN [10]
RP REVIEW.
RX PubMed=22302790; DOI=10.1113/expphysiol.2011.058214;
RA Winpenny J.P., Gray M.A.;
RT "The anoctamin (TMEM16) gene family: calcium-activated chloride channels
RT come of age.";
RL Exp. Physiol. 97:175-176(2012).
RN [11]
RP REVIEW, AND FUNCTION.
RX PubMed=21908539; DOI=10.1113/expphysiol.2011.058206;
RA Kunzelmann K., Schreiber R., Kmit A., Jantarajit W., Martins J.R.,
RA Faria D., Kongsuphol P., Ousingsawat J., Tian Y.;
RT "Expression and function of epithelial anoctamins.";
RL Exp. Physiol. 97:184-192(2012).
RN [12]
RP REVIEW, AND FUNCTION.
RX PubMed=22002868; DOI=10.1113/expphysiol.2011.058248;
RA Sanders K.M., Zhu M.H., Britton F., Koh S.D., Ward S.M.;
RT "Anoctamins and gastrointestinal smooth muscle excitability.";
RL Exp. Physiol. 97:200-206(2012).
RN [13]
RP FUNCTION, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22634729; DOI=10.1038/nn.3111;
RA Cho H., Yang Y.D., Lee J., Lee B., Kim T., Jang Y., Back S.K., Na H.S.,
RA Harfe B.D., Wang F., Raouf R., Wood J.N., Oh U.;
RT "The calcium-activated chloride channel anoctamin 1 acts as a heat sensor
RT in nociceptive neurons.";
RL Nat. Neurosci. 15:1015-1021(2012).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23840801; DOI=10.1371/journal.pone.0067989;
RA Jeon J.H., Paik S.S., Chun M.H., Oh U., Kim I.B.;
RT "Presynaptic Localization and Possible Function of Calcium-Activated
RT Chloride Channel Anoctamin 1 in the Mammalian Retina.";
RL PLoS ONE 8:e67989-e67989(2013).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24913262; DOI=10.1111/apha.12323;
RA Svenningsen P., Nielsen M.R., Marcussen N., Walter S., Jensen B.L.;
RT "TMEM16A is a Ca(2+) -activated Cl(-) channel expressed in the renal
RT collecting duct.";
RL Acta Physiol. 212:166-174(2014).
RN [16]
RP INTERACTION WITH TRPV4.
RX PubMed=24509911; DOI=10.1096/fj.13-243436;
RA Takayama Y., Shibasaki K., Suzuki Y., Yamanaka A., Tominaga M.;
RT "Modulation of water efflux through functional interaction between TRPV4
RT and TMEM16A/anoctamin 1.";
RL FASEB J. 28:2238-2248(2014).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=25779870; DOI=10.1085/jgp.201411348;
RA Amjad A., Hernandez-Clavijo A., Pifferi S., Maurya D.K., Boccaccio A.,
RA Franzot J., Rock J., Menini A.;
RT "Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated
RT chloride current in mouse vomeronasal sensory neurons.";
RL J. Gen. Physiol. 145:285-301(2015).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28963502; DOI=10.1038/s41598-017-10910-0;
RA Benedetto R., Ousingsawat J., Wanitchakool P., Zhang Y., Holtzman M.J.,
RA Amaral M., Rock J.R., Schreiber R., Kunzelmann K.;
RT "Epithelial Chloride Transport by CFTR Requires TMEM16A.";
RL Sci. Rep. 7:12397-12397(2017).
RN [19]
RP DISRUPTION PHENOTYPE.
RX PubMed=29928889; DOI=10.1016/j.lfs.2018.06.019;
RA Seo K.H., Jin Y., Jung S.Y., Lee S.H.;
RT "Comprehensive behavioral analyses of anoctamin1/TMEM16A-conditional
RT knockout mice.";
RL Life Sci. 207:323-331(2018).
RN [20]
RP ERRATUM OF PUBMED:29928889.
RX PubMed=30630631; DOI=10.1016/j.lfs.2018.12.049;
RA Seo K.H., Jin Y., Jung S.Y., Lee S.H.;
RL Life Sci. 218:346-346(2019).
RN [21]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=31175367; DOI=10.1093/biolre/ioz096;
RA Qu M., Lu P., Bellve K., Fogarty K., Lifshitz L., Shi F., Zhuge R.;
RT "Smooth muscle cell-specific TMEM16A deletion does not alter Ca2+
RT signaling, uterine contraction, gestation length, or litter size in mice.";
RL Biol. Reprod. 101:318-327(2019).
RN [22]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30586313; DOI=10.1096/fj.201801333rrr;
RA Benedetto R., Cabrita I., Schreiber R., Kunzelmann K.;
RT "TMEM16A is indispensable for basal mucus secretion in airways and
RT intestine.";
RL FASEB J. 33:4502-4512(2019).
RN [23]
RP FUNCTION, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=31147466; DOI=10.1073/pnas.1901067116;
RA Hong G.S., Lee S.H., Lee B., Choi J.H., Oh S.J., Jang Y., Hwang E.M.,
RA Kim H., Jung J., Kim I.B., Oh U.;
RT "ANO1/TMEM16A regulates process maturation in radial glial cells in the
RT developing brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:12494-12499(2019).
RN [24]
RP CALCIUM-BINDING, AND MUTAGENESIS OF GLU-425; LYS-428; ASP-883 AND ASP-888.
RX PubMed=33378669; DOI=10.1016/j.celrep.2020.108570;
RA Le S.C., Yang H.;
RT "An Additional Ca2+ Binding Site Allosterically Controls TMEM16A
RT Activation.";
RL Cell Rep. 33:108570-108570(2020).
RN [25]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=34433575; DOI=10.1523/eneuro.0179-21.2021;
RA Hernandez-Clavijo A., Sarno N., Gonzalez-Velandia K.Y., Degen R., Fleck D.,
RA Rock J.R., Spehr M., Menini A., Pifferi S.;
RT "TMEM16A and TMEM16B Modulate Pheromone-Evoked Action Potential Firing in
RT Mouse Vomeronasal Sensory Neurons.";
RL ENeuro 8:0-0(2021).
RN [26]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=34089532; DOI=10.1113/jp281645;
RA Guarascio D.M., Gonzalez-Velandia K.Y., Hernandez-Clavijo A., Menini A.,
RA Pifferi S.;
RT "Functional expression of TMEM16A in taste bud cells.";
RL J. Physiol. (Lond.) 599:3697-3714(2021).
RN [27]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=35129434; DOI=10.7554/elife.72251;
RA Maul A., Huebner A.K., Strenzke N., Moser T., Ruebsamen R., Jovanovic S.,
RA Huebner C.A.;
RT "The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+
RT waves and promotes the refinement of auditory brainstem networks in mice.";
RL Elife 11:0-0(2022).
RN [28]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=35135993; DOI=10.1097/j.pain.0000000000002611;
RA Kim H., Kim H., Cho H., Lee B., Lu H.J., Kim K., Chung S., Shim W.S.,
RA Shin Y.K., Dong X., Wood J.N., Oh U.;
RT "Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G
RT protein receptor-dependent itch.";
RL Pain 0:0-0(2022).
RN [29] {ECO:0007744|PDB:5NL2}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.60 ANGSTROMS), FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-515; ARG-535; LYS-588 AND
RP LYS-645.
RX PubMed=28561733; DOI=10.7554/elife.26232;
RA Paulino C., Neldner Y., Lam A.K., Kalienkova V., Brunner J.D., Schenck S.,
RA Dutzler R.;
RT "Structural basis for anion conduction in the calcium-activated chloride
RT channel TMEM16A.";
RL Elife 6:0-0(2017).
RN [30] {ECO:0007744|PDB:5OYB, ECO:0007744|PDB:5OYG}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.75 ANGSTROMS) OF APOPROTEIN AND IN
RP COMPLEX WITH CALCIUM, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY,
RP DISULFIDE BONDS, AND MUTAGENESIS OF ILE-550; TYR-593; GLY-644; ASN-651;
RP GLY-656; PRO-658 AND ASN-730.
RX PubMed=29236691; DOI=10.1038/nature24652;
RA Paulino C., Kalienkova V., Lam A.K.M., Neldner Y., Dutzler R.;
RT "Activation mechanism of the calcium-activated chloride channel TMEM16A
RT revealed by cryo-EM.";
RL Nature 552:421-425(2017).
RN [31] {ECO:0007744|PDB:6BGI, ECO:0007744|PDB:6BGJ}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 1-907 OF APOPROTEIN
RP AND IN COMPLEX WITH CALCIUM, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT,
RP TOPOLOGY, AND MUTAGENESIS OF ASN-546; ASN-591; TYR-593; ILE-596; VAL-599;
RP SER-639; LEU-643; GLU-654; GLN-709; PHE-712; PHE-716; ASP-784; TYR-791 AND
RP HIS-807.
RX PubMed=29236684; DOI=10.1038/nature25024;
RA Dang S., Feng S., Tien J., Peters C.J., Bulkley D., Lolicato M., Zhao J.,
RA Zuberbuhler K., Ye W., Qi L., Chen T., Craik C.S., Jan Y.N.,
RA Minor D.L. Jr., Cheng Y., Jan L.Y.;
RT "Cryo-EM structures of the TMEM16A calcium-activated chloride channel.";
RL Nature 552:426-429(2017).
CC -!- FUNCTION: Calcium-activated chloride channel (CaCC) (PubMed:28561733,
CC PubMed:29236691, PubMed:29236684, PubMed:25779870, PubMed:28963502,
CC PubMed:22634729, PubMed:31147466, PubMed:34433575, PubMed:34089532,
CC PubMed:24913262, PubMed:35135993, PubMed:23840801). Plays a role in
CC transepithelial anion transport and smooth muscle contraction
CC (PubMed:28561733, PubMed:29236691, PubMed:29236684). Required for the
CC normal functioning of the interstitial cells of Cajal (ICCs) which
CC generate electrical pacemaker activity in gastrointestinal smooth
CC muscles. Acts as a major contributor to basal and stimulated chloride
CC conductance in airway epithelial cells and plays an important role in
CC tracheal cartilage development. Required for CFTR activation by
CC enhancing endoplasmic reticulum Ca(2+) store release and is also
CC required for CFTR membrane expression (By similarity). Required for
CC basal and ATP-dependent mucus secretion in airways and intestine,
CC probably by controlling exocytosis of mucus-filled granules by
CC providing Ca(2+) to an apical signaling compartment (PubMed:30586313).
CC Contributes to airway mucus expression induced by interleukins IL3 and
CC IL8 and by the asthma-associated protein CLCA1 and is required for
CC expression of mucin MUC5AC (By similarity). However, was shown in
CC another study not to be required for MUC5AC expression (By similarity).
CC Plays a role in the propagation of Ca(2+) waves in Kolliker's organ in
CC the cochlea and contributes to the refinement of auditory brainstem
CC circuitries prior to hearing onset (PubMed:35129434). In vomeronasal
CC sensory neurons, modulates spontaneous firing patterns in the absence
CC of stimuli as well as the firing pattern of pheromone-evoked activity
CC (PubMed:34433575). Responsible for calcium-activated chloride channel
CC activity in type I taste cells of the vallate papillae
CC (PubMed:34089532). Acts as a heat sensor in nociceptive neurons
CC (PubMed:22634729). In dorsal root ganglion neurons, plays a role in
CC mediating non-histaminergic Mas-related G-protein coupled receptor
CC (MRGPR)-dependent itching, acting as a downstream effector of MRGPRs
CC (PubMed:35135993). In the developing brain, required for the Ca(2+)-
CC dependent process extension of radial glial cells (PubMed:31147466).
CC {ECO:0000250|UniProtKB:Q5XXA6, ECO:0000269|PubMed:18585372,
CC ECO:0000269|PubMed:18724360, ECO:0000269|PubMed:21908539,
CC ECO:0000269|PubMed:22002868, ECO:0000269|PubMed:22075693,
CC ECO:0000269|PubMed:22634729, ECO:0000269|PubMed:24913262,
CC ECO:0000269|PubMed:25779870, ECO:0000269|PubMed:28561733,
CC ECO:0000269|PubMed:28963502, ECO:0000269|PubMed:29236684,
CC ECO:0000269|PubMed:29236691, ECO:0000269|PubMed:30586313,
CC ECO:0000269|PubMed:31147466, ECO:0000269|PubMed:34089532,
CC ECO:0000269|PubMed:34433575, ECO:0000269|PubMed:35129434,
CC ECO:0000269|PubMed:35135993}.
CC -!- ACTIVITY REGULATION: ATP and calmodulin are essential for its
CC activation. Channel activity is inhibited by CFTR protein and by
CC chloride inhibitors such as niflumic acid (NFA) and 4,4'-
CC diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) (By similarity).
CC Activated by heat with activation seen at temperatures above 44 degrees
CC Celsius (PubMed:22634729). Activated by BDNF in radial glial cells
CC (PubMed:31147466). {ECO:0000250|UniProtKB:Q5XXA6,
CC ECO:0000269|PubMed:22634729, ECO:0000269|PubMed:31147466}.
CC -!- SUBUNIT: Homodimer (PubMed:28561733, PubMed:29236691, PubMed:29236684).
CC Interacts with CFTR (By similarity). Interacts with TRPV4
CC (PubMed:24509911). {ECO:0000250|UniProtKB:Q5XXA6,
CC ECO:0000269|PubMed:24509911, ECO:0000269|PubMed:28561733,
CC ECO:0000269|PubMed:29236684, ECO:0000269|PubMed:29236691}.
CC -!- INTERACTION:
CC Q8BHY3; Q8BHY3: Ano1; NbExp=2; IntAct=EBI-11795280, EBI-11795280;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:18585372, ECO:0000269|PubMed:22075693,
CC ECO:0000269|PubMed:24913262, ECO:0000269|PubMed:28561733,
CC ECO:0000269|PubMed:29236684, ECO:0000269|PubMed:29236691}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:28561733,
CC ECO:0000269|PubMed:29236684, ECO:0000269|PubMed:29236691}. Presynapse
CC {ECO:0000269|PubMed:23840801}. Note=In differentiating airway
CC epithelial cells, predominantly intracellular at day 0 but is apically
CC localized by day 30 (By similarity). Expressed in the presynapse of
CC retinal neurons (PubMed:23840801). {ECO:0000250|UniProtKB:Q5XXA6,
CC ECO:0000269|PubMed:23840801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BHY3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BHY3-2; Sequence=VSP_025672;
CC -!- TISSUE SPECIFICITY: Expressed at the apical surface of the vomeronasal
CC epithelium (at protein level) (PubMed:25779870, PubMed:34433575).
CC Expressed in the lateral and septal nasal glands (at protein level)
CC (PubMed:25779870). Highly expressed in pulmonary bronchiole epithelial
CC cells, pancreatic and submandibular gland acinar cells, kidney proximal
CC tubule, all retinal cell layers, most sensory cells of dorsal root
CC ganglia, Leydig cells and spermatocytes (at protein level). In the
CC dorsal root ganglia, detected in small-diameter nociceptive neurons and
CC in larger myelinated neurons (at protein level) (PubMed:22634729). In
CC the dorsal root ganglia, expressed in MrgprA3-positive neurons (at
CC protein level) (PubMed:35135993). In the developing brain, highly
CC expressed in the ventricular zone and subventricular zone at E12.5 and
CC E14.5 where it is detected in radial glial cells but not in neurons
CC with expression dramatically decreased at P1 (at protein level)
CC (PubMed:31147466). Highly expressed in the endometrial stroma (at
CC protein level) (PubMed:31175367). In taste buds of the vallate
CC papillae, expressed in the apical region of type I taste cells (at
CC protein level) (PubMed:34089532). In the kidney, expressed in the
CC collecting duct (at protein level) (PubMed:24913262). In the retina,
CC strongly expressed in the outer and inner plexiform layers, weakly
CC expressed in some somata in the inner nuclear layer and ganglion cell
CC layer and not expressed in the outer nuclear layer (at protein level)
CC (PubMed:23840801). Expressed in various retinal neurons including rod
CC bipolar cells (at protein level) (PubMed:23840801). Expressed in eye,
CC brain, myometrium and endometrium with higher levels in endometrium
CC than myometrium in estrus and day 18 pregnant mice (PubMed:31175367).
CC Not detected in uterine smooth muscle cells (PubMed:31175367).
CC Expressed at high levels in the thyroid gland and gastrointestinal
CC muscles. {ECO:0000269|PubMed:18585372, ECO:0000269|PubMed:18724360,
CC ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:22634729,
CC ECO:0000269|PubMed:23840801, ECO:0000269|PubMed:24913262,
CC ECO:0000269|PubMed:25779870, ECO:0000269|PubMed:31147466,
CC ECO:0000269|PubMed:31175367, ECO:0000269|PubMed:34089532,
CC ECO:0000269|PubMed:34433575, ECO:0000269|PubMed:35135993}.
CC -!- DEVELOPMENTAL STAGE: In the developing respiratory system, expressed in
CC epithelium of trachea and lung at 12.5 dpc and 14.5 dpc but not
CC detected in distal epithelial tips. Expressed in the mesenchyme
CC adjacent to the proximal conducting airway epithelium at 14.5 dpc but
CC not at 16.5 dpc. Epithelial expression persists at 16.5 dpc. At 18.5
CC dpc, high levels detected only in epithelial cells of terminal sacules.
CC In the developing gastrointestinal tract, expressed in the esophageal
CC mesenchyme and epithelium of posterior stomach and intestine. In the
CC developing skeleton, expressed in the perichondria of the neural arch
CC of developing vertebrae at 14.5 dpc and 16.5 dpc. In developing skin,
CC expression is restricted to basal layers of the epidermis at 16.5 dpc.
CC {ECO:0000269|PubMed:18729231}.
CC -!- DOMAIN: The region spanning the fifth and sixth transmembrane domains
CC probably forms the pore-forming region.
CC -!- DISRUPTION PHENOTYPE: Mice display severe tracheomalacia with gaps in
CC the tracheal cartilage rings along the entire length of the trachea
CC (PubMed:18585372). 90% of mutants die within the first nine days of
CC postnatal life and no mutants survive longer than 30 days postpartum
CC (PubMed:18585372). Embryonic radial glial cells exhibit significantly
CC shorter processes and mutant embryos display abnormal cortical
CC organization and decreased cortical thickness (PubMed:31147466).
CC Conditional knockout in mature vomeronasal sensory neurons abolishes
CC calcium-activated chloride currents but does not affect Tmem16b
CC expression or glomerular development in the accessory olfactory bulb
CC (PubMed:25779870, PubMed:34433575). Conditional knockout in intestinal
CC and respiratory epithelial cells abolishes both calcium-activated
CC chloride channel activity and CFTR-dependent chloride secretion
CC (PubMed:28963502). Conditional knockout in ciliated airway epithelial
CC cells results in inhibition of basal airway mucus secretion with
CC accumulation of mucus in airway club cells (PubMed:30586313).
CC Conditional knockout in intestinal epithelial cells results in
CC accumulation of mucus in both large and small intestinal goblet cells
CC (PubMed:30586313). Conditional knockout in Syn1-expressing cells
CC results in impaired social behavior, depressive-like behavior and
CC decreased weight but does not affect locomotor activity, cognitive
CC function or motor coordination (PubMed:29928889). Conditional knockout
CC in dorsal root ganglion neurons results in reduction of heat-sensitve
CC Cl- currents and a pronounced analgesic effect in response to heat
CC (PubMed:22634729). Conditional knockout in dorsal root ganglion neurons
CC results in reduced Mas-related G-protein coupled receptor-dependent
CC itching (PubMed:35135993). Conditional knockout in the inner ear does
CC not affect morphological development of the organ of Corti but impairs
CC pre-hearing cochlear activity and spontaneous burst firing as well as
CC sensitivity and frequency selectivity of sound-evoked firing of neurons
CC of the medial nucleus of the trapezoid body (MNTB) (PubMed:35129434).
CC Conditional knockout in smooth muscle cells does not alter Ca2+
CC signaling, uterine contraction, gestation length, or litter size
CC (PubMed:31175367). RNAi-mediated knockdown reduces calcium-activated
CC chloride currents and saliva production (PubMed:18724360). RNAi-
CC mediated knockdown results in a pronounced analgesic effect in response
CC to heat (PubMed:22634729). {ECO:0000269|PubMed:18585372,
CC ECO:0000269|PubMed:18724360, ECO:0000269|PubMed:22634729,
CC ECO:0000269|PubMed:25779870, ECO:0000269|PubMed:28963502,
CC ECO:0000269|PubMed:29928889, ECO:0000269|PubMed:30586313,
CC ECO:0000269|PubMed:31147466, ECO:0000269|PubMed:31175367,
CC ECO:0000269|PubMed:34433575, ECO:0000269|PubMed:35129434,
CC ECO:0000269|PubMed:35135993}.
CC -!- MISCELLANEOUS: The term 'anoctamin' was coined because these channels
CC are anion selective and are predicted to have eight (OCT) transmembrane
CC segments. There is some dissatisfaction in the field with the Ano
CC nomenclature because it is not certain that all the members of this
CC family are anion channels or have the 8-transmembrane topology.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the anoctamin family. {ECO:0000305}.
CC -!- CAUTION: Contains ten transmembrane regions, not eight as predicted.
CC {ECO:0000269|PubMed:28561733, ECO:0000269|PubMed:29236684,
CC ECO:0000269|PubMed:29236691}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06062.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC26230.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC26398.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC35051.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AK028991; BAC26230.1; ALT_INIT; mRNA.
DR EMBL; AK029329; BAC26398.1; ALT_INIT; mRNA.
DR EMBL; AK052589; BAC35051.1; ALT_SEQ; mRNA.
DR EMBL; BC006062; AAH06062.1; ALT_INIT; mRNA.
DR EMBL; BC062959; AAH62959.1; -; mRNA.
DR CCDS; CCDS40202.2; -. [Q8BHY3-1]
DR CCDS; CCDS57600.1; -. [Q8BHY3-2]
DR RefSeq; NP_001229278.1; NM_001242349.1. [Q8BHY3-2]
DR RefSeq; NP_848757.4; NM_178642.5. [Q8BHY3-1]
DR PDB; 5NL2; EM; 6.60 A; A/B=1-960.
DR PDB; 5OYB; EM; 3.75 A; A/B=1-960.
DR PDB; 5OYG; EM; 4.06 A; A/B=1-960.
DR PDB; 6BGI; EM; 3.80 A; A/B=1-907.
DR PDB; 6BGJ; EM; 3.80 A; A/B=1-907.
DR PDB; 7B5C; EM; 3.70 A; A/B=1-960.
DR PDB; 7B5D; EM; 3.30 A; A/B=1-960.
DR PDB; 7B5E; EM; 4.10 A; A/B=1-960.
DR PDBsum; 5NL2; -.
DR PDBsum; 5OYB; -.
DR PDBsum; 5OYG; -.
DR PDBsum; 6BGI; -.
DR PDBsum; 6BGJ; -.
DR PDBsum; 7B5C; -.
DR PDBsum; 7B5D; -.
DR PDBsum; 7B5E; -.
DR AlphaFoldDB; Q8BHY3; -.
DR SMR; Q8BHY3; -.
DR IntAct; Q8BHY3; 1.
DR STRING; 10090.ENSMUSP00000112616; -.
DR BindingDB; Q8BHY3; -.
DR ChEMBL; CHEMBL4105874; -.
DR TCDB; 1.A.17.1.25; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; Q8BHY3; 1 site.
DR iPTMnet; Q8BHY3; -.
DR PhosphoSitePlus; Q8BHY3; -.
DR EPD; Q8BHY3; -.
DR MaxQB; Q8BHY3; -.
DR PaxDb; Q8BHY3; -.
DR PRIDE; Q8BHY3; -.
DR ProteomicsDB; 296309; -. [Q8BHY3-1]
DR ProteomicsDB; 296310; -. [Q8BHY3-2]
DR Antibodypedia; 30667; 1377 antibodies from 39 providers.
DR DNASU; 101772; -.
DR Ensembl; ENSMUST00000033393; ENSMUSP00000033393; ENSMUSG00000031075. [Q8BHY3-2]
DR GeneID; 101772; -.
DR KEGG; mmu:101772; -.
DR CTD; 55107; -.
DR MGI; MGI:2142149; Ano1.
DR VEuPathDB; HostDB:ENSMUSG00000031075; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000157182; -.
DR HOGENOM; CLU_006685_1_2_1; -.
DR InParanoid; Q8BHY3; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q8BHY3; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 101772; 2 hits in 69 CRISPR screens.
DR ChiTaRS; Ano1; mouse.
DR PRO; PR:Q8BHY3; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8BHY3; protein.
DR Bgee; ENSMUSG00000031075; Expressed in parotid gland and 285 other tissues.
DR ExpressionAtlas; Q8BHY3; baseline and differential.
DR Genevisible; Q8BHY3; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005227; F:calcium activated cation channel activity; ISO:MGI.
DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0015111; F:iodide transmembrane transporter activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0006812; P:cation transport; ISO:MGI.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:1901653; P:cellular response to peptide; ISO:MGI.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IDA:UniProtKB.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0106091; P:glial cell projection elongation; IMP:UniProtKB.
DR GO; GO:0015705; P:iodide transport; ISO:MGI.
DR GO; GO:0070254; P:mucus secretion; IMP:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0072657; P:protein localization to membrane; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0060438; P:trachea development; IMP:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR InterPro; IPR032394; Anoct_dimer.
DR InterPro; IPR007632; Anoctamin.
DR InterPro; IPR031287; Anoctamin-1.
DR PANTHER; PTHR12308; PTHR12308; 1.
DR PANTHER; PTHR12308:SF13; PTHR12308:SF13; 1.
DR Pfam; PF16178; Anoct_dimer; 1.
DR Pfam; PF04547; Anoctamin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Cell projection; Chloride; Chloride channel; Developmental protein;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..960
FT /note="Anoctamin-1"
FT /id="PRO_0000288436"
FT TOPO_DOM 1..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 334..354
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 355..406
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 407..427
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 428..493
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 515..542
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 543..563
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 564..581
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 582..602
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 603..631
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 632..652
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 653..699
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 700..720
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 721..741
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 742..758
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 759..779
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 780..866
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TRANSMEM 867..887
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT TOPO_DOM 888..960
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT REGION 92..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 928..960
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 425
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:33378669"
FT BINDING 651
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:29236691"
FT BINDING 654
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:29236691"
FT BINDING 702
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:29236691"
FT BINDING 705
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:29236691"
FT BINDING 734
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:29236691"
FT BINDING 738
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:29236691"
FT BINDING 883
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:33378669"
FT BINDING 888
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:33378669"
FT SITE 428
FT /note="Unlikely to bind calcium but may play an important
FT structural role"
FT /evidence="ECO:0000269|PubMed:33378669"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XXA6"
FT CARBOHYD 806
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 370..395
FT /evidence="ECO:0000269|PubMed:29236691,
FT ECO:0007744|PDB:5OYB, ECO:0007744|PDB:5OYG"
FT DISULFID 379..836
FT /evidence="ECO:0000269|PubMed:29236691,
FT ECO:0007744|PDB:5OYB, ECO:0007744|PDB:5OYG"
FT DISULFID 382..386
FT /evidence="ECO:0000269|PubMed:29236691,
FT ECO:0007744|PDB:5OYB, ECO:0007744|PDB:5OYG"
FT DISULFID 625..630
FT /evidence="ECO:0000269|PubMed:29236691,
FT ECO:0007744|PDB:5OYB, ECO:0007744|PDB:5OYG"
FT VAR_SEQ 448..451
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025672"
FT MUTAGEN 425
FT /note="E->A,K: Increased Ca(2+) sensitivity."
FT /evidence="ECO:0000269|PubMed:33378669"
FT MUTAGEN 428
FT /note="K->A,E: Decreased Ca(2+) sensitivity."
FT /evidence="ECO:0000269|PubMed:33378669"
FT MUTAGEN 515
FT /note="R->A: Decreased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:28561733"
FT MUTAGEN 535
FT /note="R->A: Decreased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:28561733"
FT MUTAGEN 546
FT /note="N->D: Decreased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 550
FT /note="I->A: Low constitutive channel activity. Decreased
FT threshold for activation by calcium."
FT /evidence="ECO:0000269|PubMed:29236684,
FT ECO:0000269|PubMed:29236691"
FT MUTAGEN 588
FT /note="K->A,Q: Decreased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:23021219,
FT ECO:0000269|PubMed:28561733"
FT MUTAGEN 591
FT /note="N->A: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 593
FT /note="Y->D: Decreased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 596
FT /note="I->A: Decreased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 599
FT /note="V->A: Increased threshold for activation by calcium.
FT Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 599
FT /note="V->K,L,R: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 621
FT /note="R->E: Reduced anion permeability and increased
FT cation permeability."
FT /evidence="ECO:0000269|PubMed:18724360"
FT MUTAGEN 625
FT /note="C->A: No effect of cysteine-modifying agent MTSET on
FT ion permeability in contrast to wild-type where MTSET
FT blocks current."
FT /evidence="ECO:0000269|PubMed:18724360"
FT MUTAGEN 630
FT /note="C->A: No effect of cysteine-modifying agent MTSET on
FT ion permeability in contrast to wild-type where MTSET
FT blocks current."
FT /evidence="ECO:0000269|PubMed:18724360"
FT MUTAGEN 635
FT /note="C->A: No effect of cysteine-modifying agent MTSET on
FT ion permeability in contrast to wild-type where MTSET
FT blocks current."
FT /evidence="ECO:0000269|PubMed:18724360"
FT MUTAGEN 639
FT /note="S->A: Decreased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 643
FT /note="L->A: Increased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 644
FT /note="G->A: Decreased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236691"
FT MUTAGEN 644
FT /note="G->P: Low constitutive channel activity. Decreased
FT threshold for activation by calcium."
FT /evidence="ECO:0000269|PubMed:29236691"
FT MUTAGEN 645
FT /note="K->A: Decreased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:28561733"
FT MUTAGEN 645
FT /note="K->E: Reduced anion permeability and increased
FT cation permeability."
FT /evidence="ECO:0000269|PubMed:18724360"
FT MUTAGEN 651
FT /note="N->A: Strongly increased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236691"
FT MUTAGEN 654
FT /note="E->A: Strongly increased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 656
FT /note="G->A,P: No effect on threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236691"
FT MUTAGEN 658
FT /note="P->A,G: Moderately increased threshold for
FT activation by calcium."
FT /evidence="ECO:0000269|PubMed:29236691"
FT MUTAGEN 668
FT /note="K->E: Reduced anion permeability and increased
FT cation permeability."
FT /evidence="ECO:0000269|PubMed:18724360"
FT MUTAGEN 709
FT /note="Q->A: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 712
FT /note="F->A: Decreased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 716
FT /note="F->A: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 730
FT /note="N->A: Strongly increased threshold for activation by
FT calcium."
FT /evidence="ECO:0000269|PubMed:29236691"
FT MUTAGEN 784
FT /note="D->A: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 791
FT /note="Y->A: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 807
FT /note="H->A: Increased permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:29236684"
FT MUTAGEN 883
FT /note="D->A,K: Increased Ca(2+) sensitivity."
FT /evidence="ECO:0000269|PubMed:33378669"
FT MUTAGEN 888
FT /note="D->A,K,N: Decreased Ca(2+) sensitivity."
FT /evidence="ECO:0000269|PubMed:33378669"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 203..205
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 206..212
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 243..256
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 268..274
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 297..304
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 317..324
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 326..359
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 364..370
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 381..385
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 391..395
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 396..401
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 407..438
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 453..465
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 491..518
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 524..528
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 537..566
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 573..600
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 602..606
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 610..612
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 617..619
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 631..650
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 686..691
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 700..716
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 717..719
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 723..744
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 759..781
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 786..794
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 797..800
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 804..808
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 809..813
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 818..820
FT /evidence="ECO:0007829|PDB:7B5D"
FT TURN 826..829
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 834..840
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 845..849
FT /evidence="ECO:0007829|PDB:7B5D"
FT STRAND 851..853
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 855..885
FT /evidence="ECO:0007829|PDB:7B5D"
FT HELIX 891..909
FT /evidence="ECO:0007829|PDB:7B5D"
SQ SEQUENCE 960 AA; 110916 MW; BFD0112FD310CE88 CRC64;
MRVPEKYSTL PAEDRSVHIV NICAIEDLGY LPSEGTLLNS LSVDPDAECK YGLYFRDGKR
KVDYILVYHH KRASGSRTLA RRGLQNDMVL GTRSVRQDQP LPGKGSPVDA GSPEVPMDYH
EDDKRFRREE YEGNLLEAGL ELENDEDTKI HGVGFVKIHA PWHVLCREAE FLKLKMPTKK
VYHISETRGL LKTINSVLQK ITDPIQPKVA EHRPQTTKRL SYPFSREKQH LFDLTDRDSF
FDSKTRSTIV YEILKRTTCT KAKYSMGITS LLANGVYSAA YPLHDGDYEG DNVEFNDRKL
LYEEWASYGV FYKYQPIDLV RKYFGEKVGL YFAWLGAYTQ MLIPASIVGV IVFLYGCATV
DENIPSMEMC DQRYNITMCP LCDKTCSYWK MSSACATARA SHLFDNPATV FFSVFMALWA
ATFMEHWKRK QMRLNYRWDL TGFEEEEEAV KDHPRAEYEA RVLEKSLRKE SRNKETDKVK
LTWRDRFPAY FTNLVSIIFM IAVTFAIVLG VIIYRISTAA ALAMNSSPSV RSNIRVTVTA
TAVIINLVVI ILLDEVYGCI ARWLTKIEVP KTEKSFEERL TFKAFLLKFV NSYTPIFYVA
FFKGRFVGRP GDYVYIFRSF RMEECAPGGC LMELCIQLSI IMLGKQLIQN NLFEIGIPKM
KKFIRYLKLR RQSPSDREEY VKRKQRYEVD FNLEPFAGLT PEYMEMIIQF GFVTLFVASF
PLAPLFALLN NIIEIRLDAK KFVTELRRPV AIRAKDIGIW YNILRGVGKL AVIINAFVIS
FTSDFIPRLV YLYMYSQNGT MHGFVNHTLS SFNVSDFQNG TAPNDPLDLG YEVQICRYKD
YREPPWSEHK YDISKDFWAV LAARLAFVIV FQNLVMFMSD FVDWVIPDIP KDISQQIHKE
KVLMVELFMR EEQGKQQLLD TWMEKEKPRD VPCNNHSPTT HPEAGDGSPV PSYEYHGDAL
