ANO3_MOUSE
ID ANO3_MOUSE Reviewed; 981 AA.
AC A2AHL1; A2AHL0;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Anoctamin-3 {ECO:0000250|UniProtKB:Q9BYT9};
DE AltName: Full=Transmembrane protein 16C {ECO:0000312|EMBL:CAM25697.1};
GN Name=Ano3 {ECO:0000250|UniProtKB:Q9BYT9};
GN Synonyms=Tmem16c {ECO:0000312|EMBL:CAM25697.1,
GN ECO:0000312|MGI:MGI:3613666};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {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 [3]
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 [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=23532839; DOI=10.1074/jbc.m113.457937;
RA Suzuki J., Fujii T., Imao T., Ishihara K., Kuba H., Nagata S.;
RT "Calcium-dependent phospholipid scramblase activity of TMEM16 protein
RT family members.";
RL J. Biol. Chem. 288:13305-13316(2013).
RN [6]
RP FUNCTION, AND INTERACTION WITH KCNT1.
RX PubMed=23872594; DOI=10.1038/nn.3468;
RA Huang F., Wang X., Ostertag E.M., Nuwal T., Huang B., Jan Y.N.,
RA Basbaum A.I., Jan L.Y.;
RT "TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and
RT regulates pain processing.";
RL Nat. Neurosci. 16:1284-1290(2013).
CC -!- FUNCTION: Has calcium-dependent phospholipid scramblase activity;
CC scrambles phosphatidylcholine and galactosylceramide (PubMed:23532839).
CC Does not exhibit calcium-activated chloride channel (CaCC) activity
CC (PubMed:23532839). Seems to act as potassium channel regulator and may
CC inhibit pain signaling; can facilitate KCNT1/Slack channel activity by
CC promoting its full single-channel conductance at very low sodium
CC concentrations and by increasing its sodium sensitivity
CC (PubMed:23872594). {ECO:0000269|PubMed:23532839,
CC ECO:0000269|PubMed:23872594}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:23532839};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573;
CC Evidence={ECO:0000305|PubMed:23532839};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine(out) = a
CC beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine(in);
CC Xref=Rhea:RHEA:38899, ChEBI:CHEBI:18390;
CC Evidence={ECO:0000269|PubMed:23532839};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38900;
CC Evidence={ECO:0000305|PubMed:23532839};
CC -!- SUBUNIT: Interacts with KCNT1/Slack. {ECO:0000269|PubMed:23872594}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}. Note=Shows an intracellular localization.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A2AHL1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2AHL1-2; Sequence=VSP_052958, VSP_052959;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in neuronal tissues.
CC Expressed in brain. {ECO:0000269|PubMed:20056604,
CC ECO:0000269|PubMed:23532839}.
CC -!- DEVELOPMENTAL STAGE: In the developing gastrointestinal tract,
CC expressed in the intestinal epithelium at 14.5 dpc and in an incomplete
CC ring of cells in the mesenchyme of the esophagus, stomach and small
CC intestine at 16.5 dpc. In the developing skeleton, expressed in the
CC perichondria of the neural arch of developing vertebrae at 14.5 dpc and
CC 16.5 dpc. At 14.5 dpc, also expressed in perichondria of developing
CC ribs. At 14.5 dpc and 16.5 dpc, detected in dorsal root ganglia and
CC neural tube. In developing skin, expression is detected in the most
CC suprabasal layers at 16.5 dpc. Not detected in the lung at 14.5 dpc or
CC 16.5 dpc. {ECO:0000269|PubMed:18729231}.
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:Q9BYT9}.
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DR EMBL; AL731700; CAM18324.1; -; Genomic_DNA.
DR EMBL; AL731779; CAM18324.1; JOINED; Genomic_DNA.
DR EMBL; AL731700; CAM18325.1; -; Genomic_DNA.
DR EMBL; AL731779; CAM18325.1; JOINED; Genomic_DNA.
DR EMBL; BX005257; CAM18325.1; JOINED; Genomic_DNA.
DR EMBL; AL731779; CAM25696.1; -; Genomic_DNA.
DR EMBL; AL731700; CAM25696.1; JOINED; Genomic_DNA.
DR EMBL; AL731779; CAM25697.1; -; Genomic_DNA.
DR EMBL; AL731700; CAM25697.1; JOINED; Genomic_DNA.
DR EMBL; BX005257; CAM25697.1; JOINED; Genomic_DNA.
DR EMBL; BX005257; CAM27817.1; -; Genomic_DNA.
DR EMBL; AL731700; CAM27817.1; JOINED; Genomic_DNA.
DR EMBL; AL731779; CAM27817.1; JOINED; Genomic_DNA.
DR CCDS; CCDS50658.1; -. [A2AHL1-1]
DR RefSeq; NP_001121575.1; NM_001128103.2. [A2AHL1-1]
DR AlphaFoldDB; A2AHL1; -.
DR SMR; A2AHL1; -.
DR BioGRID; 230734; 4.
DR STRING; 10090.ENSMUSP00000097219; -.
DR SwissLipids; SLP:000000377; -.
DR GlyGen; A2AHL1; 4 sites.
DR iPTMnet; A2AHL1; -.
DR PhosphoSitePlus; A2AHL1; -.
DR EPD; A2AHL1; -.
DR jPOST; A2AHL1; -.
DR PaxDb; A2AHL1; -.
DR PRIDE; A2AHL1; -.
DR ProteomicsDB; 282108; -. [A2AHL1-1]
DR ProteomicsDB; 282109; -. [A2AHL1-2]
DR Antibodypedia; 25359; 116 antibodies from 25 providers.
DR Ensembl; ENSMUST00000099623; ENSMUSP00000097219; ENSMUSG00000074968. [A2AHL1-1]
DR GeneID; 228432; -.
DR KEGG; mmu:228432; -.
DR UCSC; uc008lmy.1; mouse. [A2AHL1-2]
DR UCSC; uc012caw.2; mouse. [A2AHL1-1]
DR CTD; 63982; -.
DR MGI; MGI:3613666; Ano3.
DR VEuPathDB; HostDB:ENSMUSG00000074968; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000156257; -.
DR HOGENOM; CLU_006685_1_3_1; -.
DR InParanoid; A2AHL1; -.
DR OMA; PCANHVK; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; A2AHL1; -.
DR TreeFam; TF314265; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 228432; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Ano3; mouse.
DR PRO; PR:A2AHL1; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2AHL1; protein.
DR Bgee; ENSMUSG00000074968; Expressed in caudate-putamen and 97 other tissues.
DR ExpressionAtlas; A2AHL1; baseline and differential.
DR Genevisible; A2AHL1; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005254; F:chloride channel activity; IBA:GO_Central.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0061591; P:calcium activated galactosylceramide scrambling; IDA:MGI.
DR GO; GO:0061590; P:calcium activated phosphatidylcholine scrambling; IDA:MGI.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0050982; P:detection of mechanical stimulus; ISO:MGI.
DR GO; GO:0016048; P:detection of temperature stimulus; ISO:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR InterPro; IPR032394; Anoct_dimer.
DR InterPro; IPR007632; Anoctamin.
DR InterPro; IPR031292; Anoctamin-3.
DR PANTHER; PTHR12308; PTHR12308; 1.
DR PANTHER; PTHR12308:SF16; PTHR12308:SF16; 1.
DR Pfam; PF16178; Anoct_dimer; 1.
DR Pfam; PF04547; Anoctamin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Lipid transport;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..981
FT /note="Anoctamin-3"
FT /id="PRO_0000353188"
FT TOPO_DOM 1..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..469
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 491..550
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 551..571
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 572..592
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 614..640
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 641..661
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 662..761
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 762..782
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 783..810
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 811..831
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 832..914
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 915..935
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 936..981
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 866
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 625..637
FT /note="EYPRTESEWENSF -> GKFIFLILLVVSK (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_052958"
FT VAR_SEQ 638..981
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_052959"
SQ SEQUENCE 981 AA; 114568 MW; E851D80BC49F4977 CRC64;
MVHHSGSIQS FKQQKGMNIS KSEITTEASL KPSRRSLPCL AQSYAHSKSL SQSASLFQST
ESESQAPTSV TFLSADKPEH VTSEESRKDS TLKCSFADLS DFCLALGKDK DYLDESEHAN
YDRSRLLNDF VTKDKPASKT KLSKNDMSYI ASSGLLFKDG KKRIDYILVY RKTNIQYDKR
NTFEKNLRAE GLMLEKEPAI ANPDIMFIKI HIPWDTLCKY AERLNIRVPF RKKCYYTDQK
NKSKSRVQNY FKRIKKWMSQ NPMVLDKSAF PELEESDCYT GPFSRARIHH FIINNKDTFF
SNATRSRIVY HMLERTKYEN GISKVGIRKL ITNGSYIAAF PPHEGAYKSS LPIKTHGPQN
NRHLLYERWA RWGMWYKHQP LDLIRMYFGE KIGLYFAWLG WYTGMLIPAA VVGLCVFFYG
LVTMNESQVS QEICKATEVF MCPLCDKNCS LQRLNDSCIY AKVTYLFDNG GTVFFAIFMA
IWATVFLEFW KRRRSILTYT WDLIEWEEEE ETLRPQFEAK YYRMEVINPI TGKPEPHQPS
SDKVTRLLVS VSGIFFMISL VITAVFAVVV YRLVVMEQFA SFKWNFVKQH WQFATSGAAV
CINFIIIMLL NLAYEKIAYL LTNLEYPRTE SEWENSFALK MFLFQFVNLN SSIFYIAFFL
GRFVGHPGKY NKLFERWRLE ECHPSGCLID LCLQMGVIMF LKQIWNNFME LGYPLIQNWW
SRHKIKRGIQ DASIPQWEND WNLQPMNIHG LMDEYLEMVL QFGFTTIFVA AFPLAPLLAL
LNNIIEIRLD AYKFVTQWRR PLPARATDIG IWLGILEGIG ILAVITNAFV IAITSDYIPR
FVYEYKYGPC ANHVKQNENC LKGYVNNSLS FFDLSELGMG KSGYCRYRDY RGPPWSSKPY
EFTLQYWHIL AARLAFIIVF EHLVFGIKSF IAYLIPDIPK GLRERIRREK YLVQEMMYEA
ELEHLQQQRR KSGQPIHHEW P
