ANO6_MOUSE
ID ANO6_MOUSE Reviewed; 911 AA.
AC Q6P9J9; Q8C242;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Anoctamin-6;
DE AltName: Full=Small-conductance calcium-activated nonselective cation channel;
DE Short=SCAN channel;
DE AltName: Full=Transmembrane protein 16F;
GN Name=Ano6;
GN Synonyms=Tmem16f {ECO:0000303|PubMed:21107324,
GN ECO:0000303|PubMed:30785399};
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 MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Dendritic cell;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
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 [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-494; ASN-785 AND ASN-803.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, and Spleen;
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 [6]
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 [7]
RP FUNCTION.
RX PubMed=21107324; DOI=10.1038/nature09583;
RA Suzuki J., Umeda M., Sims P.J., Nagata S.;
RT "Calcium-dependent phospholipid scrambling by TMEM16F.";
RL Nature 468:834-838(2010).
RN [8]
RP ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY.
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 FUNCTION, DISRUPTION PHENOTYPE, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP ASP-409; GLN-559 AND GLU-667.
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 FUNCTION, AND CATALYTIC ACTIVITY.
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 [13]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22936354; DOI=10.1002/jbmr.1751;
RA Ehlen H.W., Chinenkova M., Moser M., Munter H.M., Krause Y., Gross S.,
RA Brachvogel B., Wuelling M., Kornak U., Vortkamp A.;
RT "Inactivation of Anoctamin-6/Tmem16f, a regulator of phosphatidylserine
RT scrambling in osteoblasts, leads to decreased mineral deposition in
RT skeletal tissues.";
RL J. Bone Miner. Res. 28:246-259(2013).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-409; PHE-518; TYR-563;
RP ILE-612 AND ASP-703.
RX PubMed=31015464; DOI=10.1038/s41467-019-09778-7;
RA Le T., Jia Z., Le S.C., Zhang Y., Chen J., Yang H.;
RT "An inner activation gate controls TMEM16F phospholipid scrambling.";
RL Nat. Commun. 10:1846-1846(2019).
RN [15] {ECO:0007744|PDB:6QP6, ECO:0007744|PDB:6QPB, ECO:0007744|PDB:6QPC, ECO:0007744|PDB:6QPI}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS), FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, TOPOLOGY, DISULFIDE BONDS, AND MUTAGENESIS OF
RP ARG-478; GLY-615; GLU-624 AND GLU-667.
RX PubMed=30785399; DOI=10.7554/elife.44365;
RA Alvadia C., Lim N.K., Clerico Mosina V., Oostergetel G.T., Dutzler R.,
RA Paulino C.;
RT "Cryo-EM structures and functional characterization of the murine lipid
RT scramblase TMEM16F.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Small-conductance calcium-activated nonselective cation
CC (SCAN) channel which acts as a regulator of phospholipid scrambling in
CC platelets, osteoblasts and fetal thymocytes. Phospholipid scrambling
CC results in surface exposure of phosphatidylserine which in platelets is
CC essential to trigger the clotting system whereas in osteoblasts is
CC essential for the deposition of hydroxyapatite during bone
CC mineralization. Has calcium-dependent phospholipid scramblase activity;
CC scrambles phosphatidylserine, phosphatidylcholine and
CC galactosylceramide. Can generate outwardly rectifying chloride channel
CC currents in airway epithelial cells and Jurkat T lymphocytes.
CC {ECO:0000269|PubMed:21107324, ECO:0000269|PubMed:21908539,
CC ECO:0000269|PubMed:22936354, ECO:0000269|PubMed:23021219,
CC ECO:0000269|PubMed:23532839, ECO:0000269|PubMed:30785399,
CC ECO:0000269|PubMed:31015464}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-
CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663,
CC ChEBI:CHEBI:57262; Evidence={ECO:0000269|PubMed:23532839,
CC ECO:0000269|PubMed:31015464};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664;
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 -!- 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 -!- ACTIVITY REGULATION: Exhibits synergistic gating by Ca(2+) and voltage.
CC Inhibited by some non-specific cation channel blockers such as:
CC ruthenium red, 2-aminoethyl diphenylborinate (2APB), gadolinium and
CC cadmium ions. {ECO:0000269|PubMed:23021219}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:30785399}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30785399};
CC Multi-pass membrane protein {ECO:0000269|PubMed:30785399}. Note=Shows
CC an intracellular localization. {ECO:0000250|UniProtKB:Q4KMQ2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P9J9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P9J9-2; Sequence=VSP_015654, VSP_015655;
CC -!- TISSUE SPECIFICITY: Predominant expression seen in epithelial tissues.
CC Also found in skeletal system where it is primarily expressed in
CC osteoblasts. {ECO:0000269|PubMed:20056604,
CC ECO:0000269|PubMed:22936354}.
CC -!- DEVELOPMENTAL STAGE: At 14.5 dpc, expressed in lung epithelium and
CC mesenchyme. At 16.5 dpc, expressed in esophageal epithelium and
CC mesenchyme. In the caudal digestive tract, detected in small intestine
CC epithelium at 14.5 dpc. Also detected at 14.5 dpc in epithelium and
CC mesenchyme of trachea, ovary, kidney and stomach. In the developing
CC skeleton, expressed in developing rib perichondria at 14.5 dpc. Also
CC expressed in the neural tube and dorsal root ganglia at 14.5 dpc. In
CC developing skin, expression is restricted to basal layers of the
CC epidermis at 16.5 dpc. {ECO:0000269|PubMed:18729231}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, and display no major
CC morphological defects. They exhibit deficiencies in Ca(2+)-dependent
CC phospholipid scramblase activity in platelets and defects in blood
CC coagulation (PubMed:23021219). They also show reduced skeleton size and
CC skeletal deformities. {ECO:0000269|PubMed:22936354,
CC ECO:0000269|PubMed:23021219}.
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:30785399}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK089300; BAC40833.1; -; mRNA.
DR EMBL; BC060732; AAH60732.1; -; mRNA.
DR CCDS; CCDS37184.1; -. [Q6P9J9-1]
DR RefSeq; NP_001240742.1; NM_001253813.1.
DR RefSeq; NP_780553.2; NM_175344.4. [Q6P9J9-1]
DR PDB; 6P46; EM; 3.50 A; A/B=1-911.
DR PDB; 6P47; EM; 3.90 A; A/B=1-911.
DR PDB; 6P48; EM; 3.20 A; A/B=1-911.
DR PDB; 6P49; EM; 3.30 A; A/B=1-911.
DR PDB; 6QP6; EM; 3.20 A; A/B=1-911.
DR PDB; 6QPB; EM; 3.60 A; A/B=1-911.
DR PDB; 6QPC; EM; 3.50 A; A/B=1-911.
DR PDB; 6QPI; EM; 3.30 A; A/B=1-911.
DR PDBsum; 6P46; -.
DR PDBsum; 6P47; -.
DR PDBsum; 6P48; -.
DR PDBsum; 6P49; -.
DR PDBsum; 6QP6; -.
DR PDBsum; 6QPB; -.
DR PDBsum; 6QPC; -.
DR PDBsum; 6QPI; -.
DR AlphaFoldDB; Q6P9J9; -.
DR SMR; Q6P9J9; -.
DR STRING; 10090.ENSMUSP00000071770; -.
DR SwissLipids; SLP:000000373; -.
DR GlyGen; Q6P9J9; 6 sites.
DR iPTMnet; Q6P9J9; -.
DR PhosphoSitePlus; Q6P9J9; -.
DR SwissPalm; Q6P9J9; -.
DR EPD; Q6P9J9; -.
DR jPOST; Q6P9J9; -.
DR MaxQB; Q6P9J9; -.
DR PaxDb; Q6P9J9; -.
DR PeptideAtlas; Q6P9J9; -.
DR PRIDE; Q6P9J9; -.
DR ProteomicsDB; 281994; -. [Q6P9J9-1]
DR ProteomicsDB; 281995; -. [Q6P9J9-2]
DR ABCD; Q6P9J9; 1 sequenced antibody.
DR Antibodypedia; 42608; 135 antibodies from 22 providers.
DR Ensembl; ENSMUST00000071874; ENSMUSP00000071770; ENSMUSG00000064210. [Q6P9J9-1]
DR GeneID; 105722; -.
DR KEGG; mmu:105722; -.
DR UCSC; uc007xju.2; mouse. [Q6P9J9-1]
DR CTD; 196527; -.
DR MGI; MGI:2145890; Ano6.
DR VEuPathDB; HostDB:ENSMUSG00000064210; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000158969; -.
DR HOGENOM; CLU_006685_1_3_1; -.
DR InParanoid; Q6P9J9; -.
DR OMA; EKVTPRW; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q6P9J9; -.
DR TreeFam; TF314265; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 105722; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Ano6; mouse.
DR PRO; PR:Q6P9J9; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q6P9J9; protein.
DR Bgee; ENSMUSG00000064210; Expressed in otolith organ and 253 other tissues.
DR ExpressionAtlas; Q6P9J9; baseline and differential.
DR Genevisible; Q6P9J9; MM.
DR GO; GO:0034707; C:chloride channel complex; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005227; F:calcium activated cation channel activity; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IBA:GO_Central.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; ISO:MGI.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IDA:UniProtKB.
DR GO; GO:0002543; P:activation of blood coagulation via clotting cascade; ISO:MGI.
DR GO; GO:0032060; P:bleb assembly; IMP:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IMP:UniProtKB.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; IMP:MGI.
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:0061589; P:calcium activated phosphatidylserine scrambling; IDA:MGI.
DR GO; GO:0061588; P:calcium activated phospholipid scrambling; IMP:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IGI:UniProtKB.
DR GO; GO:0006812; P:cation transport; ISO:MGI.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IDA:MGI.
DR GO; GO:0002407; P:dendritic cell chemotaxis; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0045794; P:negative regulation of cell volume; IMP:UniProtKB.
DR GO; GO:0097045; P:phosphatidylserine exposure on blood platelet; ISO:MGI.
DR GO; GO:0045332; P:phospholipid translocation; IDA:UniProtKB.
DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IMP:UniProtKB.
DR GO; GO:0046931; P:pore complex assembly; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:UniProtKB.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:0034767; P:positive regulation of ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:UniProtKB.
DR GO; GO:1903766; P:positive regulation of potassium ion export across plasma membrane; ISS:BHF-UCL.
DR GO; GO:0035590; P:purinergic nucleotide receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR InterPro; IPR032394; Anoct_dimer.
DR InterPro; IPR007632; Anoctamin.
DR InterPro; IPR031295; Anoctamin-6.
DR PANTHER; PTHR12308; PTHR12308; 1.
DR PANTHER; PTHR12308:SF21; PTHR12308:SF21; 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; Chloride;
KW Chloride channel; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Lipid transport; Membrane; Metal-binding; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..911
FT /note="Anoctamin-6"
FT /id="PRO_0000191758"
FT TOPO_DOM 1..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 323..376
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 398..456
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 457..477
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 478..510
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 511..531
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 532..552
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 553..573
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 574..602
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 603..622
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 623..664
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 665..685
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 707..723
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 724..744
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 745..837
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TRANSMEM 838..858
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30785399"
FT TOPO_DOM 859..911
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30785399"
FT BINDING 624
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30785399"
FT BINDING 667
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30785399"
FT BINDING 670
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30785399"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 778
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 785
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 803
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT DISULFID 331..372
FT /evidence="ECO:0000269|PubMed:30785399,
FT ECO:0007744|PDB:6QP6, ECO:0007744|PDB:6QPC"
FT DISULFID 338..365
FT /evidence="ECO:0000269|PubMed:30785399,
FT ECO:0007744|PDB:6QP6, ECO:0007744|PDB:6QPB,
FT ECO:0007744|PDB:6QPC"
FT DISULFID 349..807
FT /evidence="ECO:0000269|PubMed:30785399,
FT ECO:0007744|PDB:6QP6, ECO:0007744|PDB:6QPB,
FT ECO:0007744|PDB:6QPC"
FT DISULFID 352..356
FT /evidence="ECO:0000269|PubMed:30785399,
FT ECO:0007744|PDB:6QPC"
FT DISULFID 596..601
FT /evidence="ECO:0000269|PubMed:30785399,
FT ECO:0007744|PDB:6QP6, ECO:0007744|PDB:6QPB,
FT ECO:0007744|PDB:6QPC"
FT VAR_SEQ 1..427
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015654"
FT VAR_SEQ 428..436
FT /note="NHVVINEIT -> MALMAESLC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015655"
FT MUTAGEN 370
FT /note="K->A: No effect on lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 409
FT /note="D->G: Increased speed of phospholipid scrambling."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 409
FT /note="D->G: Reduced channel activity and sensitivity to
FT Ca(2+)."
FT /evidence="ECO:0000269|PubMed:23021219"
FT MUTAGEN 478
FT /note="R->A: Decreased lipid scramblase and ion channel
FT activity. Requires lower calcium levels for activation of
FT ion channel activity."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 518
FT /note="F->A: Increased speed of phospholipid scrambling.
FT Constitutive scramblase activity at basal cytosolic calcium
FT levels; when associated with A-563 and A-612."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 518
FT /note="F->E,K,Q: Constitutive lipid scramblase activity at
FT basal cytosolic calcium levels."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 518
FT /note="F->L: Decreased lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 518
FT /note="F->W: Slightly increased lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 559
FT /note="Q->K: Moderately decreased sensitivity to activation
FT by calcium."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 559
FT /note="Q->K: Slower channel activation. Increased
FT permeability to chloride ions."
FT /evidence="ECO:0000269|PubMed:23021219"
FT MUTAGEN 563
FT /note="Y->A: Increased speed of phospholipid scrambling.
FT Requires lower calcium levels for activation of scramblase
FT and ion channel activity. Constitutive scramblase activity
FT at basal cytosolic calcium levels; when associated with A-
FT 518 and A-612."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 563
FT /note="Y->K,Q: Constitutive lipid scramblase activity at
FT basal cytosolic calcium levels."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 563
FT /note="Y->S: No effect on lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 563
FT /note="Y->W: Loss of lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 612
FT /note="I->A: Increased speed of phospholipid scrambling.
FT Constitutive scramblase activity at basal cytosolic calcium
FT levels; when associated with A-518 and A-563."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 612
FT /note="I->E,K: Constitutive lipid scramblase activity at
FT basal cytosolic calcium levels."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 612
FT /note="I->W: Decreased lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:31015464"
FT MUTAGEN 615
FT /note="G->A: Requires lower calcium levels for activation
FT of scramblase and ion channel activity."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 623
FT /note="Q->F: No effect on lipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 624
FT /note="E->Q: Expected to disrupt calcium binding. Loss of
FT scramblase and ion channel activity."
FT /evidence="ECO:0000269|PubMed:30785399"
FT MUTAGEN 667
FT /note="E->Q: Requires much higher calcium levels for the
FT activation of scramblase and ion channel activity."
FT /evidence="ECO:0000269|PubMed:23021219,
FT ECO:0000269|PubMed:30785399"
FT MUTAGEN 703
FT /note="D->R: Expected to disrupt calcium binding. Loss of
FT scramblase activity."
FT /evidence="ECO:0000269|PubMed:31015464"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 91..103
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 121..129
FT /evidence="ECO:0007829|PDB:6QP6"
FT TURN 137..141
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 206..219
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 234..238
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 268..271
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 286..289
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 290..296
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 297..309
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 312..325
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:6P46"
FT STRAND 330..335
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 361..370
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 372..375
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 378..381
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 382..407
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 421..426
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 452..455
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 457..479
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 481..485
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 505..536
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 544..550
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 552..572
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 574..577
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 589..591
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 602..613
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 616..619
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 620..628
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 629..632
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 639..645
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 650..653
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 655..657
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 665..678
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 680..684
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 688..708
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 720..722
FT /evidence="ECO:0007829|PDB:6QPC"
FT HELIX 726..746
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 748..750
FT /evidence="ECO:0007829|PDB:6P46"
FT HELIX 751..759
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 761..763
FT /evidence="ECO:0007829|PDB:6P48"
FT TURN 778..780
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 781..786
FT /evidence="ECO:0007829|PDB:6QP6"
FT HELIX 798..801
FT /evidence="ECO:0007829|PDB:6QP6"
FT STRAND 808..811
FT /evidence="ECO:0007829|PDB:6P48"
FT STRAND 816..818
FT /evidence="ECO:0007829|PDB:6P49"
FT TURN 819..822
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 826..856
FT /evidence="ECO:0007829|PDB:6P48"
FT HELIX 862..874
FT /evidence="ECO:0007829|PDB:6QP6"
SQ SEQUENCE 911 AA; 106255 MW; 33D7A6EF02635B39 CRC64;
MQMMTRKVLL NMELEEDDDE DGDIVLENFD QTIVCPTFGS LENQQDFRTP EFEEFNGKPD
SLFFTDGQRR IDFILVYEDE SKKENNKKGT NEKQKRKRQA YESNLICHGL QLEATRSVSD
DKLVFVKVHA PWEVLCTYAE IMHIKLPLKP NDLKTRSPFG NLNWFTKVLR VNESVIKPEQ
EFFTAPFEKS RMNDFYILDR DSFFNPATRS RIVYFILSRV KYQVMNNVNK FGINRLVSSG
IYKAAFPLHD CRFNYESEDI SCPSERYLLY REWAHPRSIY KKQPLDLIRK YYGEKIGIYF
AWLGYYTQML LLAAVVGVAC FLYGYLDQDN CTWSKEVCDP DIGGQILMCP QCDRLCPFWR
LNITCESSKK LCIFDSFGTL IFAVFMGVWV TLFLEFWKRR QAELEYEWDT VELQQEEQAR
PEYEAQCNHV VINEITQEEE RIPFTTCGKC IRVTLCASAV FFWILLIIAS VIGIIVYRLS
VFIVFSTTLP KNPNGTDPIQ KYLTPQMATS ITASIISFII IMILNTIYEK VAIMITNFEL
PRTQTDYENS LTMKMFLFQF VNYYSSCFYI AFFKGKFVGY PGDPVYLLGK YRSEECDPGG
CLLELTTQLT IIMGGKAIWN NIQEVLLPWV MNLIGRYKRV SGSEKITPRW EQDYHLQPMG
KLGLFYEYLE MIIQFGFVTL FVASFPLAPL LALVNNILEI RVDAWKLTTQ FRRMVPEKAQ
DIGAWQPIMQ GIAILAVVTN AMIIAFTSDM IPRLVYYWSF SIPPYGDHTY YTMDGYINNT
LSVFNITDFK NTDKENPYIG LGNYTLCRYR DFRNPPGHPQ EYKHNIYYWH VIAAKLAFII
VMEHIIYSVK FFISYAIPDV SKITKSKIKR EKYLTQKLLH ESHLKDLTKN MGIIAERIGG
TVDNSVRPKL E
