ID ANO2_MOUSE Reviewed; 1002 AA.
AC Q8CFW1; C4N788; Q8C8N6;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 27-MAR-2024, entry version 132.
DE RecName: Full=Anoctamin-2 {ECO:0000250|UniProtKB:Q9NQ90};
DE AltName: Full=Transmembrane protein 16B {ECO:0000312|EMBL:AAH33409.1};
GN Name=Ano2 {ECO:0000250|UniProtKB:Q9NQ90};
GN Synonyms=Tmem16b {ECO:0000312|EMBL:AAH33409.1};
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], FUNCTION, TRANSPORTER ACTIVITY, GLYCOSYLATION,
RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH DLG4, MUTAGENESIS OF
RP 1000-THR--ASN-1002, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=19474308; DOI=10.1523/jneurosci.5546-08.2009;
RA Stoehr H., Heisig J.B., Benz P.M., Schoeberl S., Milenkovic V.M.,
RA Strauss O., Aartsen W.M., Wijnholds J., Weber B.H.F., Schulz H.L.;
RT "TMEM16B, a novel protein with calcium-dependent chloride channel activity,
RT associates with a presynaptic protein complex in photoreceptor terminals.";
RL J. Neurosci. 29:6809-6818(2009).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAC32073.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-543.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC32073.1};
RC TISSUE=Retina {ECO:0000312|EMBL:BAC32073.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH33409.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 59-1002.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH33409.1};
RC TISSUE=Eye {ECO:0000312|EMBL:AAH33409.1};
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] {ECO:0000305}
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 [5]
RP FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=19475416; DOI=10.1007/s00424-009-0684-9;
RA Pifferi S., Dibattista M., Menini A.;
RT "TMEM16B induces chloride currents activated by calcium in mammalian
RT cells.";
RL Pflugers Arch. 458:1023-1038(2009).
RN [6]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=19561302; DOI=10.1073/pnas.0903304106;
RA Stephan A.B., Shum E.Y., Hirsh S., Cygnar K.D., Reisert J., Zhao H.;
RT "ANO2 is the cilial calcium-activated chloride channel that may mediate
RT olfactory amplification.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:11776-11781(2009).
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.
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 SUBUNIT.
RX PubMed=23576756; DOI=10.1073/pnas.1303672110;
RA Tien J., Lee H.Y., Minor D.L. Jr., Jan Y.N., Jan L.Y.;
RT "Identification of a dimerization domain in the TMEM16A calcium-activated
RT chloride channel (CaCC).";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6352-6357(2013).
CC -!- FUNCTION: Calcium-activated chloride channel (CaCC) which may play a
CC role in olfactory signal transduction. Odorant molecules bind to odor-
CC sensing receptors (OSRs), leading to an increase in calcium entry that
CC activates CaCC current which amplifies the depolarization of the OSR
CC cells, ANO2 seems to be the underlying chloride channel involved in
CC this process. May mediate light perception amplification in retina.
CC {ECO:0000269|PubMed:19474308, ECO:0000269|PubMed:19475416,
CC ECO:0000269|PubMed:19561302, ECO:0000269|PubMed:22075693}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:19474308,
CC ECO:0000269|PubMed:19475416};
CC -!- ACTIVITY REGULATION: Channel activity is repressed by chloride
CC inhibitors; strongly by niflumic acid (NFA), partially by flufenamic
CC acid (FFA), and only slightly by meclofenamic acid (MFA), 5-Nitro-2-(3-
CC phenylpropylamino)benzoic acid (NPPB), 4-acetamido-4'-isothiocyanato-
CC stilben-2,2'-disulfonate (SITS), and 4,4'-diisothiocyanatostilbene-
CC 2,2'-disulfonic acid (DIDS). {ECO:0000269|PubMed:19475416}.
CC -!- SUBUNIT: Homodimer (PubMed:23576756). Component of a presynaptic
CC protein complex recruited to specialized plasma membrane domains of
CC photoreceptors. Interacts with DLG4 by its C-terminal region.
CC {ECO:0000269|PubMed:19474308, ECO:0000269|PubMed:23576756}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19474308,
CC ECO:0000269|PubMed:19561302}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in retina, especially in the
CC photoreceptor synaptic terminals, and in olfactory epithelium,
CC particularly in sensory neurons (OSNs) and cilia (at protein level).
CC Also observed in retinal pigment epithelium (RPE), olfactory bulb,
CC brain, and cortex. {ECO:0000269|PubMed:19474308,
CC ECO:0000269|PubMed:19561302, ECO:0000269|PubMed:20056604}.
CC -!- DEVELOPMENTAL STAGE: Detected in the mantle layer of the neural tube
CC and in the dorsal root ganglia at 14.5 dpc. In developing skin,
CC expression is restricted to basal layers of the epidermis at 16.5 dpc.
CC {ECO:0000269|PubMed:18729231}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:19474308}.
CC -!- MISCELLANEOUS: The term 'anoctamin' was coined because these channels
CC are anion selective and have eight (OCT) transmembrane segments. There
CC is some dissatisfaction in the field with the Ano nomenclature because
CC it is not certain that all the members of this family are anion
CC channels or have the 8-transmembrane topology.
CC -!- SIMILARITY: Belongs to the anoctamin family.
CC {ECO:0000250|UniProtKB:Q9NQ90}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH33409.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC32073.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; FJ384096; ACL36051.1; -; mRNA.
DR EMBL; AK044763; BAC32073.1; ALT_SEQ; mRNA.
DR EMBL; BC033409; AAH33409.1; ALT_INIT; mRNA.
DR CCDS; CCDS39643.2; -.
DR RefSeq; NP_705817.2; NM_153589.2.
DR RefSeq; XP_006506182.1; XM_006506119.1.
DR AlphaFoldDB; Q8CFW1; -.
DR SMR; Q8CFW1; -.
DR BioGRID; 232544; 2.
DR STRING; 10090.ENSMUSP00000125303; -.
DR BindingDB; Q8CFW1; -.
DR ChEMBL; CHEMBL4739697; -.
DR GlyCosmos; Q8CFW1; 4 sites, No reported glycans.
DR GlyGen; Q8CFW1; 4 sites.
DR iPTMnet; Q8CFW1; -.
DR PhosphoSitePlus; Q8CFW1; -.
DR PaxDb; 10090-ENSMUSP00000125303; -.
DR ProteomicsDB; 282107; -.
DR Antibodypedia; 41841; 152 antibodies from 28 providers.
DR DNASU; 243634; -.
DR Ensembl; ENSMUST00000160496.8; ENSMUSP00000125303.2; ENSMUSG00000038115.17.
DR GeneID; 243634; -.
DR KEGG; mmu:243634; -.
DR UCSC; uc009duv.1; mouse.
DR AGR; MGI:2387214; -.
DR CTD; 57101; -.
DR MGI; MGI:2387214; Ano2.
DR VEuPathDB; HostDB:ENSMUSG00000038115; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000155840; -.
DR HOGENOM; CLU_006685_1_2_1; -.
DR InParanoid; Q8CFW1; -.
DR OMA; HYVYVFD; -.
DR OrthoDB; 534027at2759; -.
DR PhylomeDB; Q8CFW1; -.
DR TreeFam; TF314265; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 243634; 0 hits in 78 CRISPR screens.
DR ChiTaRS; Ano2; mouse.
DR PRO; PR:Q8CFW1; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8CFW1; Protein.
DR Bgee; ENSMUSG00000038115; Expressed in retinal neural layer and 41 other cell types or tissues.
DR ExpressionAtlas; Q8CFW1; baseline and differential.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0097730; C:non-motile cilium; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR GO; GO:0005254; F:chloride channel activity; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0006821; P:chloride transport; IDA:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR InterPro; IPR032394; Anoct_dimer.
DR InterPro; IPR007632; Anoctamin.
DR InterPro; IPR049452; Anoctamin_TM.
DR PANTHER; PTHR12308; ANOCTAMIN; 1.
DR PANTHER; PTHR12308:SF20; ANOCTAMIN-2; 1.
DR Pfam; PF16178; Anoct_dimer; 1.
DR Pfam; PF04547; Anoctamin; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Chloride; Chloride channel; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1002
FT /note="Anoctamin-2"
FT /id="PRO_0000353187"
FT TOPO_DOM 1..364
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 386..433
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..536
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 537..557
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 558..580
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 581..601
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 602..621
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 622..642
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 643..746
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 747..767
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 768..799
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 800..820
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 821..905
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 906..926
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 927..1002
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 958..1002
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1000..1002
FT /note="DLG4 binding (PDZ)"
FT COMPBIAS 958..972
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 973..1002
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 839
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 847
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 854
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 1000..1002
FT /note="Missing: Impaired interaction with DLG4."
FT /evidence="ECO:0000269|PubMed:19474308"
SQ SEQUENCE 1002 AA; 114134 MW; 8514FC9CC13F78C7 CRC64;
MAAPGLRDIP LLPGSPRRLS SRTVARGSQG PKHGQQYLKV PGHRAPGQRD NSSLHPSQVS
RRESSRDRSV INNYLDANEP PSSEARLSRM HFHDNQRKVD YVLAYHYRKR GAHLGHGSPG
HSLAVISNGE TGKERHGGGP GDVELGPLDA LEEERREQRD EFEHNLMAAG LELEKDLESK
SQGSVFVRIH APWQVLAREA EFLKIKVPTK KMYEIKAGGS IAKKFSAILQ TLSSPLQPRV
PEHSNNRMKN LSYPFSREKM YLYNIQEKDT FFDNATRSRI VHEILKRTAC SRANNTMGIN
SLIANNIYEA AYPLHDGEYD SPGDDMNDRK LLYQEWARYG VFYKFQPIDL IRKYFGEKIG
LYFAWLGLYT SFLIPSSVIG VIVFLYGCAT IEEDIPSKEM CDHQNAFTMC PLCDKSCDYW
NLSSACGTAR ASHLFDNPAT VFFSIFMALW ATMFLENWKR LQMRLGYFWD LTGIEEEEER
SQEHSRPEYE TKVREKLLKE SGKSAVQKLE ANSPEDDEDD EDKLTWKDRF PGYLMNFASI
LFMIALTFSI VFGVIVYRIT TAAALSLNKA TRSNVRVTVT ATAVIINLVV ILILDEIYGA
VAKWLTKIEV PKTEQTFEER LILKAFLLKF VNAYSPIFYV AFFKGRFVGR PGSYVYVFDG
YRMEECAPGG CLMELCIQLS IIMLGKQLIQ NNIFEIGVPK LKKLFRKLKD ETEPGESDPD
HSKRPEQWDL DHSLEPYTGL TPEYMEMIIQ FGFVTLFVAS FPLAPVFALL NNVIEVRLDA
KKFVTELRRP DAVRTKDIGI WFDILSGIGK FSVIINAFVI AVTSDFIPRL VYQYSYSHNG
TLHGFVNHTL SFFNVSQLKE GTQPENSQFD QEVQFCRFKD YREPPWAPNP YEFSKQYWSV
LSARLAFVII FQNLVMFLSV LVDWMIPDIP TDISDQIKKE KSLLVDFFLK EEHEKVKLAD
EPTQRSQGGG DRSRRSRAAS SAPSGRSQPG SIASSGSQHT NV
//
