ANO1_HUMAN
ID ANO1_HUMAN Reviewed; 986 AA.
AC Q5XXA6; A0A2H4Y9B2; A8KAM3; E9PNA7; Q8IYY8; Q8N7V3;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Anoctamin-1;
DE AltName: Full=Discovered on gastrointestinal stromal tumors protein 1;
DE AltName: Full=Oral cancer overexpressed protein 2;
DE AltName: Full=Transmembrane protein 16A;
DE AltName: Full=Tumor-amplified and overexpressed sequence 2;
GN Name=ANO1;
GN Synonyms=DOG1 {ECO:0000303|PubMed:15215166}, ORAOV2, TAOS2, TMEM16A;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=16906560; DOI=10.1002/gcc.20371;
RA Huang X., Godfrey T.E., Gooding W.E., McCarty K.S. Jr., Gollin S.M.;
RT "Comprehensive genome and transcriptome analysis of the 11q13 amplicon in
RT human oral cancer and synteny to the 7F5 amplicon in murine oral
RT carcinoma.";
RL Genes Chromosomes Cancer 45:1058-1069(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND FUNCTION.
RX PubMed=26359375; DOI=10.1152/ajpgi.00074.2015;
RA Strege P.R., Bernard C.E., Mazzone A., Linden D.R., Beyder A.,
RA Gibbons S.J., Farrugia G.;
RT "A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater
RT sensitivity to intracellular Ca2.";
RL Am. J. Physiol. 309:G743-G749(2015).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Testis, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [6]
RP IDENTIFICATION, AND TOPOLOGY.
RX PubMed=12739008;
RA Katoh M., Katoh M.;
RT "FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome
RT 11q13, encodes the eight-transmembrane protein homologous to C12orf3,
RT C11orf25 and FLJ34272 gene products.";
RL Int. J. Oncol. 22:1375-1381(2003).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15215166; DOI=10.1016/s0002-9440(10)63279-8;
RA West R.B., Corless C.L., Chen X., Rubin B.P., Subramanian S.,
RA Montgomery K., Zhu S., Ball C.A., Nielsen T.O., Patel R., Goldblum J.R.,
RA Brown P.O., Heinrich M.C., van de Rijn M.;
RT "The novel marker, DOG1, is expressed ubiquitously in gastrointestinal
RT stromal tumors irrespective of KIT or PDGFRA mutation status.";
RL Am. J. Pathol. 165:107-113(2004).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [9]
RP REVIEW.
RX PubMed=21186280; DOI=10.1152/physiol.00030.2010;
RA Ferrera L., Caputo A., Galietta L.J.;
RT "TMEM16A protein: a new identity for Ca(2+)-dependent Cl? channels.";
RL Physiology (Bethesda) 25:357-363(2010).
RN [10]
RP REVIEW.
RX PubMed=21642943; DOI=10.1038/aps.2011.48;
RA Duran C., Hartzell H.C.;
RT "Physiological roles and diseases of Tmem16/Anoctamin proteins: are they
RT all chloride channels?";
RL Acta Pharmacol. Sin. 32:685-692(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CFTR, AND ACTIVITY
RP REGULATION.
RX PubMed=22178883; DOI=10.1159/000335765;
RA Ousingsawat J., Kongsuphol P., Schreiber R., Kunzelmann K.;
RT "CFTR and TMEM16A are separate but functionally related Cl-channels.";
RL Cell. Physiol. Biochem. 28:715-724(2011).
RN [13]
RP SUBUNIT.
RX PubMed=21056985; DOI=10.1074/jbc.m110.174847;
RA Sheridan J.T., Worthington E.N., Yu K., Gabriel S.E., Hartzell H.C.,
RA Tarran R.;
RT "Characterization of the oligomeric structure of the Ca(2+)-activated
RT Cl- channel Ano1/TMEM16A.";
RL J. Biol. Chem. 286:1381-1388(2011).
RN [14]
RP REVIEW.
RX PubMed=21607626; DOI=10.1007/s00424-011-0975-9;
RA Kunzelmann K., Tian Y., Martins J.R., Faria D., Kongsuphol P.,
RA Ousingsawat J., Thevenod F., Roussa E., Rock J., Schreiber R.;
RT "Anoctamins.";
RL Pflugers Arch. 462:195-208(2011).
RN [15]
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 [16]
RP REVIEW, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21984732; DOI=10.1113/expphysiol.2011.058198;
RA Scudieri P., Sondo E., Ferrera L., Galietta L.J.;
RT "The anoctamin family: TMEM16A and TMEM16B as calcium-activated chloride
RT channels.";
RL Exp. Physiol. 97:177-183(2012).
RN [17]
RP REVIEW.
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 [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22946059; DOI=10.1242/jcs.109553;
RA Tian Y., Schreiber R., Kunzelmann K.;
RT "Anoctamins are a family of Ca2+ activated Cl- channels.";
RL J. Cell Sci. 125:4991-4998(2012).
RN [19]
RP 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 [20]
RP ALTERNATIVE SPLICING (ISOFORM 4), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25220078; DOI=10.1111/exd.12543;
RA Ertongur-Fauth T., Hochheimer A., Buescher J.M., Rapprich S., Krohn M.;
RT "A novel TMEM16A splice variant lacking the dimerization domain contributes
RT to calcium-activated chloride secretion in human sweat gland epithelial
RT cells.";
RL Exp. Dermatol. 23:825-831(2014).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107 AND SER-196, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=28559167; DOI=10.1016/j.jsb.2017.05.009;
RA Peckys D.B., Stoerger C., Latta L., Wissenbach U., Flockerzi V.,
RA de Jonge N.;
RT "The stoichiometry of the TMEM16A ion channel determined in intact plasma
RT membranes of COS-7 cells using liquid-phase electron microscopy.";
RL J. Struct. Biol. 199:102-113(2017).
RN [23]
RP FUNCTION, AND INTERACTION WITH CFTR.
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 [24]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=31732694; DOI=10.26508/lsa.201900462;
RA Simoes F.B., Quaresma M.C., Clarke L.A., Silva I.A., Pankonien I.,
RA Railean V., Kmit A., Amaral M.D.;
RT "TMEM16A chloride channel does not drive mucus production.";
RL Life. Sci Alliance 2:0-0(2019).
RN [25]
RP FUNCTION, AND INDUCTION.
RX PubMed=33026825; DOI=10.1165/rcmb.2019-0442oc;
RA Cabrita I., Benedetto R., Wanitchakool P., Lerias J., Centeio R.,
RA Ousingsawat J., Schreiber R., Kunzelmann K.;
RT "TMEM16A Mediates Mucus Production in Human Airway Epithelial Cells.";
RL Am. J. Respir. Cell Mol. Biol. 64:50-58(2021).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISEASE.
RX PubMed=32487539; DOI=10.1136/jmedgenet-2020-106978;
RA Park J.H., Ousingsawat J., Cabrita I., Bettels R.E., Grosse-Onnebrink J.,
RA Schmalstieg C., Biskup S., Reunert J., Rust S., Schreiber R.,
RA Kunzelmann K., Marquardt T.;
RT "TMEM16A deficiency: a potentially fatal neonatal disease resulting from
RT impaired chloride currents.";
RL J. Med. Genet. 58:247-253(2021).
CC -!- FUNCTION: Calcium-activated chloride channel (CaCC) (PubMed:20056604,
CC PubMed:22178883, PubMed:21984732, PubMed:22946059, PubMed:32487539).
CC Plays a role in transepithelial anion transport and smooth muscle
CC contraction. Required for the normal functioning of the interstitial
CC cells of Cajal (ICCs) which generate electrical pacemaker activity in
CC gastrointestinal smooth muscles. Acts as a major contributor to basal
CC and stimulated chloride conductance in airway epithelial cells and
CC plays an important role in tracheal cartilage development. Required for
CC CFTR activation by enhancing endoplasmic reticulum Ca(2+) store release
CC and is also required for CFTR membrane expression (PubMed:28963502).
CC Required for basal and ATP-dependent mucus secretion in airways and
CC intestine, probably by controlling exocytosis of mucus-filled granules
CC by providing Ca(2+) to an apical signaling compartment (By similarity).
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 (PubMed:33026825). However, was shown in
CC another study not to be required for MUC5AC expression
CC (PubMed:31732694). Plays a role in the propagation of Ca(2+) waves in
CC Kolliker's organ in the cochlea and contributes to the refinement of
CC auditory brainstem circuitries prior to hearing onset (By similarity).
CC In vomeronasal sensory neurons, modulates spontaneous firing patterns
CC in the absence of stimuli as well as the firing pattern of pheromone-
CC evoked activity (By similarity). Responsible for calcium-activated
CC chloride channel activity in type I taste cells of the vallate papillae
CC (By similarity). Acts as a heat sensor in nociceptive neurons (By
CC similarity). In dorsal root ganglion neurons, plays a role in mediating
CC non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-
CC dependent itching, acting as a downstream effector of MRGPRs (By
CC similarity). In the developing brain, required for the Ca(2+)-dependent
CC process extension of radial glial cells (By similarity).
CC {ECO:0000250|UniProtKB:Q8BHY3, ECO:0000269|PubMed:20056604,
CC ECO:0000269|PubMed:21984732, ECO:0000269|PubMed:22178883,
CC ECO:0000269|PubMed:22946059, ECO:0000269|PubMed:28963502,
CC ECO:0000269|PubMed:31732694, ECO:0000269|PubMed:32487539,
CC ECO:0000269|PubMed:33026825}.
CC -!- FUNCTION: [Isoform 4]: Calcium-activated chloride channel (CaCC).
CC Contributes to calcium-activated chloride secretion in human sweat
CC gland epithelial cells. Shows increased basal chloride permeability and
CC decreased Ca(2+)-induced chloride permeability.
CC {ECO:0000269|PubMed:25220078}.
CC -!- FUNCTION: [Isoform 5]: Calcium-activated chloride channel (CaCC). Shows
CC increased sensitivity to intracellular Ca(2+).
CC {ECO:0000269|PubMed:26359375}.
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). Activated by heat
CC with activation seen at temperatures above 44 degrees Celsius (By
CC similarity). Activated by BDNF in radial glial cells (By similarity).
CC {ECO:0000250|UniProtKB:Q8BHY3, ECO:0000269|PubMed:22178883}.
CC -!- SUBUNIT: Homodimer (PubMed:21056985, PubMed:28559167). Interacts with
CC CFTR (PubMed:22178883, PubMed:28963502). Interacts with TRPV4 (By
CC similarity). {ECO:0000250|UniProtKB:Q8BHY3,
CC ECO:0000269|PubMed:21056985, ECO:0000269|PubMed:22178883,
CC ECO:0000269|PubMed:28559167, ECO:0000269|PubMed:28963502}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15215166, ECO:0000269|PubMed:20056604,
CC ECO:0000269|PubMed:21984732, ECO:0000269|PubMed:22178883,
CC ECO:0000269|PubMed:22946059, ECO:0000269|PubMed:28559167,
CC ECO:0000269|PubMed:31732694, ECO:0000269|PubMed:32487539}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q8BHY3}. Presynapse
CC {ECO:0000250|UniProtKB:Q8BHY3}. Note=In differentiating airway
CC epithelial cells, predominantly intracellular at day 0 but is apically
CC localized by day 30. Expressed in the presynapse of retinal neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q8BHY3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=TMEM16A(ac) {ECO:0000303|PubMed:25220078};
CC IsoId=Q5XXA6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5XXA6-2; Sequence=VSP_025665, VSP_025668, VSP_025669;
CC Name=3;
CC IsoId=Q5XXA6-3; Sequence=VSP_025666, VSP_025667, VSP_025668,
CC VSP_025669, VSP_025670, VSP_025671;
CC Name=4; Synonyms=TMEM16A(ac-delta-e3) {ECO:0000303|PubMed:25220078};
CC IsoId=Q5XXA6-4; Sequence=VSP_061540, VSP_025669;
CC Name=5; Synonyms=Ano1(+0) {ECO:0000303|PubMed:26359375};
CC IsoId=Q5XXA6-5; Sequence=VSP_061539, VSP_061541;
CC -!- TISSUE SPECIFICITY: Expressed in nasal epithelial cells (at protein
CC level) (PubMed:32487539). In the kidney, expressed in the collecting
CC duct (at protein level) (PubMed:24913262). Broadly expressed with
CC higher levels in liver, skeletal muscle and gastrointestinal muscles
CC (PubMed:16906560, PubMed:15215166). Expressed in eccrine sweat glands
CC (PubMed:25220078). {ECO:0000269|PubMed:15215166,
CC ECO:0000269|PubMed:16906560, ECO:0000269|PubMed:24913262,
CC ECO:0000269|PubMed:25220078, ECO:0000269|PubMed:32487539}.
CC -!- DEVELOPMENTAL STAGE: In airway epithelial cells, highly expressed
CC during cell proliferation with levels decreasing as cell
CC differentiation progresses (at protein level).
CC {ECO:0000269|PubMed:31732694}.
CC -!- INDUCTION: By IL13 (PubMed:33026825). By IL4, likely as a result of
CC IL4-induced cell proliferation (PubMed:31732694). By wounding in airway
CC epithelial cells with levels decreasing significantly during the
CC healing process (PubMed:31732694). {ECO:0000269|PubMed:31732694,
CC ECO:0000269|PubMed:33026825}.
CC -!- DOMAIN: The region spanning the fifth and sixth transmembrane domains
CC probably forms the pore-forming region. {ECO:0000250}.
CC -!- DISEASE: Note=Defects in ANO1 may be the cause of a disorder
CC characterized by impaired intestinal peristalsis, intestinal
CC pneumatosis, microalbuminuria and dysmorphic features in neonates. The
CC defective ANO1 protein is truncated, accumulates intracellularly and is
CC non-functional, resulting in the absence of Ca(2+)-activated chloride
CC currents and secondary CFTR dysfunction. {ECO:0000269|PubMed:32487539}.
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:0000250|UniProtKB:Q8BHY3}.
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DR EMBL; AY728143; AAU82085.1; -; mRNA.
DR EMBL; KY449273; AUD55143.1; -; mRNA.
DR EMBL; AK097619; BAC05123.1; -; mRNA.
DR EMBL; AK293088; BAF85777.1; -; mRNA.
DR EMBL; AP000879; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033036; AAH33036.2; -; mRNA.
DR CCDS; CCDS44663.1; -. [Q5XXA6-1]
DR RefSeq; NP_060513.5; NM_018043.5. [Q5XXA6-1]
DR RefSeq; XP_006718668.1; XM_006718605.2. [Q5XXA6-2]
DR RefSeq; XP_011543433.1; XM_011545131.2. [Q5XXA6-3]
DR AlphaFoldDB; Q5XXA6; -.
DR SMR; Q5XXA6; -.
DR BioGRID; 120417; 9.
DR IntAct; Q5XXA6; 2.
DR STRING; 9606.ENSP00000347454; -.
DR BindingDB; Q5XXA6; -.
DR ChEMBL; CHEMBL2046267; -.
DR DrugBank; DB04941; Crofelemer.
DR DrugCentral; Q5XXA6; -.
DR GuidetoPHARMACOLOGY; 708; -.
DR TCDB; 1.A.17.1.1; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; Q5XXA6; 1 site.
DR iPTMnet; Q5XXA6; -.
DR PhosphoSitePlus; Q5XXA6; -.
DR BioMuta; ANO1; -.
DR DMDM; 74708278; -.
DR EPD; Q5XXA6; -.
DR jPOST; Q5XXA6; -.
DR MassIVE; Q5XXA6; -.
DR MaxQB; Q5XXA6; -.
DR PaxDb; Q5XXA6; -.
DR PeptideAtlas; Q5XXA6; -.
DR PRIDE; Q5XXA6; -.
DR ProteomicsDB; 65854; -. [Q5XXA6-1]
DR ProteomicsDB; 65855; -. [Q5XXA6-2]
DR ProteomicsDB; 65856; -. [Q5XXA6-3]
DR Antibodypedia; 30667; 1377 antibodies from 39 providers.
DR DNASU; 55107; -.
DR Ensembl; ENST00000316296.9; ENSP00000319477.5; ENSG00000131620.18. [Q5XXA6-3]
DR Ensembl; ENST00000355303.10; ENSP00000347454.5; ENSG00000131620.18. [Q5XXA6-1]
DR Ensembl; ENST00000530676.5; ENSP00000435797.1; ENSG00000131620.18. [Q5XXA6-2]
DR GeneID; 55107; -.
DR KEGG; hsa:55107; -.
DR MANE-Select; ENST00000355303.10; ENSP00000347454.5; NM_018043.7; NP_060513.5.
DR UCSC; uc001opj.4; human. [Q5XXA6-1]
DR CTD; 55107; -.
DR DisGeNET; 55107; -.
DR GeneCards; ANO1; -.
DR HGNC; HGNC:21625; ANO1.
DR HPA; ENSG00000131620; Tissue enhanced (epididymis, salivary gland, seminal vesicle).
DR MIM; 610108; gene.
DR neXtProt; NX_Q5XXA6; -.
DR OpenTargets; ENSG00000131620; -.
DR PharmGKB; PA164715378; -.
DR VEuPathDB; HostDB:ENSG00000131620; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000157182; -.
DR HOGENOM; CLU_006685_5_2_1; -.
DR InParanoid; Q5XXA6; -.
DR OMA; SFRMEEX; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q5XXA6; -.
DR TreeFam; TF314265; -.
DR PathwayCommons; Q5XXA6; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q5XXA6; -.
DR BioGRID-ORCS; 55107; 14 hits in 1063 CRISPR screens.
DR ChiTaRS; ANO1; human.
DR GeneWiki; ANO1; -.
DR GenomeRNAi; 55107; -.
DR Pharos; Q5XXA6; Tclin.
DR PRO; PR:Q5XXA6; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q5XXA6; protein.
DR Bgee; ENSG00000131620; Expressed in caput epididymis and 142 other tissues.
DR ExpressionAtlas; Q5XXA6; baseline and differential.
DR Genevisible; Q5XXA6; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005227; F:calcium activated cation channel activity; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0015111; F:iodide transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; ISS:UniProtKB.
DR GO; GO:0006812; P:cation transport; IDA:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IMP:UniProtKB.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0106091; P:glial cell projection elongation; ISS:UniProtKB.
DR GO; GO:0015705; P:iodide transport; IMP:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0070254; P:mucus secretion; IMP:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS: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; 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 Alternative splicing; Calcium; Cell membrane; Cell projection; Chloride;
KW Chloride channel; Developmental protein; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..986
FT /note="Anoctamin-1"
FT /id="PRO_0000288435"
FT TOPO_DOM 1..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 334..354
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 355..406
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 407..427
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 428..519
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 520..540
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 541..568
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 569..589
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 590..607
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 608..628
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 629..657
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 658..678
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 679..725
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TRANSMEM 747..767
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 768..784
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 785..805
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 806..892
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 893..913
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT TOPO_DOM 914..986
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 79..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 951..986
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..93
FT /note="Polar residues"
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:0000250|UniProtKB:Q8BHY3"
FT BINDING 677
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 680
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 728
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 731
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 760
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 764
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 909
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT BINDING 914
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT SITE 428
FT /note="Unlikely to bind calcium but may play an important
FT structural role"
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 832
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 370..395
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT DISULFID 379..862
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT DISULFID 382..386
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT DISULFID 651..656
FT /evidence="ECO:0000250|UniProtKB:Q8BHY3"
FT VAR_SEQ 1..116
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025665"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025666"
FT VAR_SEQ 1
FT /note="M -> MQEGDIGLEGLPPREVPTVEAAGAVDGEGAPPGGPSAQAATM (in
FT isoform 5)"
FT /evidence="ECO:0000269|PubMed:26359375"
FT /id="VSP_061539"
FT VAR_SEQ 29..36
FT /note="GYLPSEGT -> MLTRPSQV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025667"
FT VAR_SEQ 148..180
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000269|PubMed:25220078"
FT /id="VSP_061540"
FT VAR_SEQ 267
FT /note="G -> GQGEGRKKDSALLSKRRKCGKYG (in isoform 5)"
FT /evidence="ECO:0000269|PubMed:26359375"
FT /id="VSP_061541"
FT VAR_SEQ 448..451
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_025668"
FT VAR_SEQ 476..501
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000269|PubMed:25220078,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_025669"
FT VAR_SEQ 651..700
FT /note="CAPGGCLMELCIQLSIIMLGKQLIQNNLFEIGIPKMKKLIRYLKLKQQSP
FT -> VTEILFISGSPFCLAYDLSTPCTWEKQLQHICSAKSSRFLSFLLETFLFP (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025670"
FT VAR_SEQ 701..986
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025671"
FT VARIANT 608
FT /note="F -> S (in dbSNP:rs2186797)"
FT /id="VAR_032417"
FT VARIANT 983
FT /note="G -> R (in dbSNP:rs3740722)"
FT /id="VAR_032418"
FT CONFLICT 202
FT /note="T -> A (in Ref. 3; BAF85777)"
FT /evidence="ECO:0000305"
FT CONFLICT 801
FT /note="N -> D (in Ref. 5; AAH33036)"
FT /evidence="ECO:0000305"
FT CONFLICT 948
FT /note="W -> C (in Ref. 5; AAH33036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 986 AA; 114078 MW; E30A02F91EF36FC2 CRC64;
MRVNEKYSTL PAEDRSVHII NICAIEDIGY LPSEGTLLNS LSVDPDAECK YGLYFRDGRR
KVDYILVYHH KRPSGNRTLV RRVQHSDTPS GARSVKQDHP LPGKGASLDA GSGEPPMDYH
EDDKRFRREE YEGNLLEAGL ELERDEDTKI HGVGFVKIHA PWNVLCREAE FLKLKMPTKK
MYHINETRGL LKKINSVLQK ITDPIQPKVA EHRPQTMKRL SYPFSREKQH LFDLSDKDSF
FDSKTRSTIV YEILKRTTCT KAKYSMGITS LLANGVYAAA YPLHDGDYNG ENVEFNDRKL
LYEEWARYGV FYKYQPIDLV RKYFGEKIGL YFAWLGVYTQ MLIPASIVGI IVFLYGCATM
DENIPSMEMC DQRHNITMCP LCDKTCSYWK MSSACATARA SHLFDNPATV FFSVFMALWA
ATFMEHWKRK QMRLNYRWDL TGFEEEEEAV KDHPRAEYEA RVLEKSLKKE SRNKEKRRHI
PEESTNKWKQ RVKTAMAGVK LTDKVKLTWR DRFPAYLTNL VSIIFMIAVT FAIVLGVIIY
RISMAAALAM NSSPSVRSNI RVTVTATAVI INLVVIILLD EVYGCIARWL TKIEVPKTEK
SFEERLIFKA FLLKFVNSYT PIFYVAFFKG RFVGRPGDYV YIFRSFRMEE CAPGGCLMEL
CIQLSIIMLG KQLIQNNLFE IGIPKMKKLI RYLKLKQQSP PDHEECVKRK QRYEVDYNLE
PFAGLTPEYM EMIIQFGFVT LFVASFPLAP LFALLNNIIE IRLDAKKFVT ELRRPVAVRA
KDIGIWYNIL RGIGKLAVII NAFVISFTSD FIPRLVYLYM YSKNGTMHGF VNHTLSSFNV
SDFQNGTAPN DPLDLGYEVQ ICRYKDYREP PWSENKYDIS KDFWAVLAAR LAFVIVFQNL
VMFMSDFVDW VIPDIPKDIS QQIHKEKVLM VELFMREEQD KQQLLETWME KERQKDEPPC
NHHNTKACPD SLGSPAPSHA YHGGVL
