ID ANO6_HUMAN Reviewed; 910 AA. AC Q4KMQ2; A6NNM6; B9EGG0; E7ENK4; E9PB30; E9PCT2; Q8N3Q2; DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 02-OCT-2024, entry version 161. DE RecName: Full=Anoctamin-6 {ECO:0000305}; DE AltName: Full=Small-conductance calcium-activated nonselective cation channel; DE Short=SCAN channel; DE AltName: Full=Transmembrane protein 16F; GN Name=ANO6 {ECO:0000312|HGNC:HGNC:25240}; GN Synonyms=TMEM16F {ECO:0000303|PubMed:33827113}; 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Placenta, and 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 772-910 (ISOFORM 1/2). RC TISSUE=Adipose tissue; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP TISSUE SPECIFICITY. RX PubMed=15067359; RA Katoh M., Katoh M.; RT "Identification and characterization of TMEM16E and TMEM16F genes in RT silico."; RL Int. J. Oncol. 24:1345-1349(2004). RN [5] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-493. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [6] 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 [7] RP FUNCTION, SUBCELLULAR LOCATION, AND INVOLVEMENT IN SCOTT SYNDROME. 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 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 [9] 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 [10] RP FUNCTION. RX PubMed=22006324; DOI=10.1073/pnas.1108094108; RA Martins J.R., Faria D., Kongsuphol P., Reisch B., Schreiber R., RA Kunzelmann K.; RT "Anoctamin 6 is an essential component of the outwardly rectifying chloride RT channel."; RL Proc. Natl. Acad. Sci. U.S.A. 108:18168-18172(2011). RN [11] RP 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 [12] 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 [13] RP REVIEW, AND ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY. 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 [14] 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 [15] 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 [16] 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 [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [18] RP FUNCTION (MICROBIAL INFECTION), AND INDUCTION BY SARS-COV-2 INFECTION RP (MICROBIAL INFECTION). RX PubMed=33827113; DOI=10.1038/s41586-021-03491-6; RA Braga L., Ali H., Secco I., Chiavacci E., Neves G., Goldhill D., Penn R., RA Jimenez-Guardeno J.M., Ortega-Prieto A.M., Bussani R., Cannata A., RA Rizzari G., Collesi C., Schneider E., Arosio D., Shah A.M., Barclay W.S., RA Malim M.H., Burrone J., Giacca M.; RT "Drugs that inhibit TMEM16 proteins block SARS-CoV-2 Spike-induced RT syncytia."; RL Nature 594:88-93(2021). CC -!- FUNCTION: Small-conductance calcium-activated nonselective cation CC (SCAN) channel which acts as a regulator of phospholipid scrambling in CC platelets and osteoblasts. Phospholipid scrambling results in surface CC exposure of phosphatidylserine which in platelets is essential to CC trigger the clotting system whereas in osteoblasts is essential for the CC deposition of hydroxyapatite during bone mineralization. Has calcium- CC dependent phospholipid scramblase activity; scrambles CC phosphatidylserine, phosphatidylcholine and galactosylceramide (By CC similarity). Can generate outwardly rectifying chloride channel CC currents in airway epithelial cells and Jurkat T lymphocytes. CC {ECO:0000250|UniProtKB:Q6P9J9, ECO:0000269|PubMed:20056604, CC ECO:0000269|PubMed:21107324, ECO:0000269|PubMed:21908539, CC ECO:0000269|PubMed:22006324, ECO:0000269|PubMed:22946059}. CC -!- FUNCTION: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 CC infection, is activated by spike protein which increases the amplitude CC of spontaneous Ca(2+) signals and is required for spike-mediated CC syncytia. {ECO:0000269|PubMed:33827113}. 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:0000250|UniProtKB:Q6P9J9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664; CC Evidence={ECO:0000250|UniProtKB:Q6P9J9}; 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:0000250|UniProtKB:Q6P9J9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38900; CC Evidence={ECO:0000250|UniProtKB:Q6P9J9}; 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:0000250|UniProtKB:Q6P9J9}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573; CC Evidence={ECO:0000250|UniProtKB:Q6P9J9}; CC -!- ACTIVITY REGULATION: Exhibits synergistic gating by Ca(2+) and voltage CC (By similarity). Inhibited by some non-specific cation channel blockers CC such as: ruthenium red, 2-aminoethyl diphenylborinate (2APB), CC gadolinium and cadmium ions (By similarity). CC {ECO:0000250|UniProtKB:Q6P9J9}. CC -!- ACTIVITY REGULATION: (Microbial infection) Activated by SARS CC coronavirus-2/SARS-CoV-2 spike protein. {ECO:0000269|PubMed:33827113}. CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6P9J9}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20056604, CC ECO:0000269|PubMed:21107324, ECO:0000269|PubMed:22075693, CC ECO:0000269|PubMed:22946059}; Multi-pass membrane protein CC {ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:21107324, CC ECO:0000269|PubMed:22075693, ECO:0000269|PubMed:22946059}. Note=Shows CC an intracellular localization according to PubMed:22075693. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q4KMQ2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q4KMQ2-2; Sequence=VSP_042893; CC Name=3; CC IsoId=Q4KMQ2-3; Sequence=VSP_046819; CC Name=4; CC IsoId=Q4KMQ2-4; Sequence=VSP_046820; CC -!- TISSUE SPECIFICITY: Expressed in embryonic stem cell, fetal liver, CC retina, chronic myologenous leukemia and intestinal cancer. CC {ECO:0000269|PubMed:15067359}. CC -!- INDUCTION: (Microbial infection) Expression is induced by SARS CC coronavirus-2/SARS-CoV-2 spike protein. {ECO:0000269|PubMed:33827113}. CC -!- DISEASE: Scott syndrome (SCTS) [MIM:262890]: A mild bleeding disorder CC due to impaired surface exposure of procoagulant phosphatidylserine CC (PS) on platelets and other blood cells, following activation with CC Ca(2+)-elevating agents. {ECO:0000269|PubMed:21107324}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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:Q6P9J9}. 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; AC009248; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC009778; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC063924; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC098410; AAH98410.1; -; mRNA. DR EMBL; BC136445; AAI36446.1; -; mRNA. DR EMBL; AL833405; CAD38638.1; -; mRNA. DR CCDS; CCDS31782.1; -. [Q4KMQ2-1] DR CCDS; CCDS44865.1; -. [Q4KMQ2-4] DR CCDS; CCDS44866.1; -. [Q4KMQ2-3] DR CCDS; CCDS55819.1; -. [Q4KMQ2-2] DR RefSeq; NP_001020527.2; NM_001025356.2. [Q4KMQ2-1] DR RefSeq; NP_001136150.1; NM_001142678.1. [Q4KMQ2-3] DR RefSeq; NP_001136151.1; NM_001142679.1. [Q4KMQ2-4] DR RefSeq; NP_001191732.1; NM_001204803.1. [Q4KMQ2-2] DR AlphaFoldDB; Q4KMQ2; -. DR SMR; Q4KMQ2; -. DR BioGRID; 128218; 143. DR IntAct; Q4KMQ2; 69. DR MINT; Q4KMQ2; -. DR STRING; 9606.ENSP00000409126; -. DR TCDB; 1.A.17.1.4; the calcium-dependent chloride channel (ca-clc) family. DR GlyConnect; 1014; 7 N-Linked glycans (2 sites). DR GlyCosmos; Q4KMQ2; 6 sites, 7 glycans. DR GlyGen; Q4KMQ2; 6 sites, 7 N-linked glycans (2 sites). DR iPTMnet; Q4KMQ2; -. DR PhosphoSitePlus; Q4KMQ2; -. DR SwissPalm; Q4KMQ2; -. DR BioMuta; ANO6; -. DR DMDM; 116242820; -. DR jPOST; Q4KMQ2; -. DR MassIVE; Q4KMQ2; -. DR PaxDb; 9606-ENSP00000409126; -. DR PeptideAtlas; Q4KMQ2; -. DR ProteomicsDB; 19131; -. DR ProteomicsDB; 19507; -. DR ProteomicsDB; 62203; -. [Q4KMQ2-1] DR ProteomicsDB; 62204; -. [Q4KMQ2-2] DR Pumba; Q4KMQ2; -. DR ABCD; Q4KMQ2; 1 sequenced antibody. DR Antibodypedia; 42608; 157 antibodies from 22 providers. DR DNASU; 196527; -. DR Ensembl; ENST00000320560.13; ENSP00000320087.8; ENSG00000177119.17. [Q4KMQ2-1] DR Ensembl; ENST00000423947.7; ENSP00000409126.3; ENSG00000177119.17. [Q4KMQ2-2] DR Ensembl; ENST00000425752.6; ENSP00000391417.2; ENSG00000177119.17. [Q4KMQ2-4] DR Ensembl; ENST00000441606.2; ENSP00000413137.2; ENSG00000177119.17. [Q4KMQ2-3] DR Ensembl; ENST00000680201.1; ENSP00000506222.1; ENSG00000177119.17. [Q4KMQ2-1] DR GeneID; 196527; -. DR KEGG; hsa:196527; -. DR MANE-Select; ENST00000320560.13; ENSP00000320087.8; NM_001025356.3; NP_001020527.2. DR UCSC; uc001roo.4; human. [Q4KMQ2-1] DR AGR; HGNC:25240; -. DR CTD; 196527; -. DR DisGeNET; 196527; -. DR GeneCards; ANO6; -. DR HGNC; HGNC:25240; ANO6. DR HPA; ENSG00000177119; Low tissue specificity. DR MalaCards; ANO6; -. DR MIM; 262890; phenotype. DR MIM; 608663; gene. DR neXtProt; NX_Q4KMQ2; -. DR OpenTargets; ENSG00000177119; -. DR Orphanet; 806; Scott syndrome. DR PharmGKB; PA164715690; -. DR VEuPathDB; HostDB:ENSG00000177119; -. DR eggNOG; KOG2514; Eukaryota. DR GeneTree; ENSGT00940000158969; -. DR HOGENOM; CLU_006685_1_3_1; -. DR InParanoid; Q4KMQ2; -. DR OMA; HYTMDGY; -. DR OrthoDB; 534027at2759; -. DR PhylomeDB; Q4KMQ2; -. DR TreeFam; TF314265; -. DR PathwayCommons; Q4KMQ2; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion. DR SignaLink; Q4KMQ2; -. DR SIGNOR; Q4KMQ2; -. DR BioGRID-ORCS; 196527; 14 hits in 1165 CRISPR screens. DR ChiTaRS; ANO6; human. DR GenomeRNAi; 196527; -. DR Pharos; Q4KMQ2; Tbio. DR PRO; PR:Q4KMQ2; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q4KMQ2; protein. DR Bgee; ENSG00000177119; Expressed in epithelial cell of pancreas and 192 other cell types or tissues. DR ExpressionAtlas; Q4KMQ2; baseline and differential. DR GO; GO:0009986; C:cell surface; HDA:UniProtKB. DR GO; GO:0034707; C:chloride channel complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. 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:0005229; F:intracellularly calcium-gated chloride channel activity; IMP:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0017128; F:phospholipid scramblase activity; IMP:FlyBase. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0005247; F:voltage-gated chloride channel activity; IMP:UniProtKB. DR GO; GO:0005244; F:voltage-gated monoatomic ion channel activity; ISS:UniProtKB. DR GO; GO:0002543; P:activation of blood coagulation via clotting cascade; IMP:UniProtKB. DR GO; GO:0032060; P:bleb assembly; IMP:UniProtKB. DR GO; GO:0007596; P:blood coagulation; ISS:UniProtKB. DR GO; GO:0061590; P:calcium activated phosphatidylcholine scrambling; IBA:GO_Central. DR GO; GO:0061589; P:calcium activated phosphatidylserine scrambling; IBA:GO_Central. DR GO; GO:0070588; P:calcium ion transmembrane transport; IGI:UniProtKB. DR GO; GO:1902476; P:chloride transmembrane transport; IMP:UniProtKB. DR GO; GO:0006821; P:chloride transport; IMP:UniProtKB. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome. DR GO; GO:0045794; P:negative regulation of cell volume; IMP:UniProtKB. DR GO; GO:0097045; P:phosphatidylserine exposure on blood platelet; IMP:UniProtKB. DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IMP:UniProtKB. DR GO; GO:0046931; P:pore complex assembly; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS: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; IMP:UniProtKB. DR GO; GO:0034767; P:positive regulation of monoatomic 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; ISS: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; IGI:UniProtKB. DR InterPro; IPR032394; Anoct_dimer. DR InterPro; IPR007632; Anoctamin. DR InterPro; IPR049452; Anoctamin_TM. DR PANTHER; PTHR12308; ANOCTAMIN; 1. DR PANTHER; PTHR12308:SF21; ANOCTAMIN-6; 1. DR Pfam; PF16178; Anoct_dimer; 1. DR Pfam; PF04547; Anoctamin; 1. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell membrane; Chloride; Chloride channel; KW Disulfide bond; Glycoprotein; Host-virus interaction; Ion channel; KW Ion transport; Lipid transport; Membrane; Metal-binding; KW Proteomics identification; Reference proteome; Transmembrane; KW Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1..910 FT /note="Anoctamin-6" FT /id="PRO_0000191757" FT TOPO_DOM 1..300 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 301..321 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 322..375 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 376..396 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 397..455 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 456..476 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 477..509 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 510..530 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 531..551 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 552..572 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 573..601 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 602..621 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 622..663 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 664..684 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TRANSMEM 685..705 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 706..722 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 723..743 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 744..836 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 837..857 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT TOPO_DOM 858..910 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT BINDING 623 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT BINDING 666 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT BINDING 669 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT CARBOHYD 329 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 361 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 493 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 777 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 790 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 802 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 330..371 FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT DISULFID 337..364 FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT DISULFID 348..806 FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT DISULFID 351..355 FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT DISULFID 595..600 FT /evidence="ECO:0000250|UniProtKB:Q6P9J9" FT VAR_SEQ 1..23 FT /note="MKKMSRNVLLQMEEEEDDDDGDI -> MFCAA (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_046819" FT VAR_SEQ 23 FT /note="I -> IGDVPASRRPFLTPHTHLPSSL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042893" FT VAR_SEQ 843..910 FT /note="HVIYSVKFFISYAIPDVSKRTKSKIQREKYLTQKLLHENHLKDMTKNMGVIA FT ERMIEAVDNNLRPKSE -> YLALLPRLGHSGMILAHCNLRLPVDCCMCYRFVDEIRLL FT EQLTSDFIDSLYYIFSISIISIFFSVTFFFLLLSLGPTPCFSVSNFLS (in FT isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_046820" FT VARIANT 128 FT /note="A -> T (in dbSNP:rs2162321)" FT /id="VAR_028109" FT CONFLICT 837 FT /note="F -> L (in Ref. 2; AAH98410)" FT /evidence="ECO:0000305" SQ SEQUENCE 910 AA; 106165 MW; 8F7F1CB78FAAEB78 CRC64; MKKMSRNVLL QMEEEEDDDD GDIVLENLGQ TIVPDLGSLE SQHDFRTPEF EEFNGKPDSL FFNDGQRRID FVLVYEDESR KETNKKGTNE KQRRKRQAYE SNLICHGLQL EATRSVLDDK LVFVKVHAPW EVLCTYAEIM HIKLPLKPND LKNRSSAFGT LNWFTKVLSV DESIIKPEQE FFTAPFEKNR MNDFYIVDRD AFFNPATRSR IVYFILSRVK YQVINNVSKF GINRLVNSGI YKAAFPLHDC KFRRQSEDPS CPNERYLLYR EWAHPRSIYK KQPLDLIRKY YGEKIGIYFA WLGYYTQMLL LAAVVGVACF LYGYLNQDNC TWSKEVCHPD IGGKIIMCPQ CDRLCPFWKL NITCESSKKL CIFDSFGTLV FAVFMGVWVT LFLEFWKRRQ AELEYEWDTV ELQQEEQARP EYEARCTHVV INEITQEEER IPFTAWGKCI RITLCASAVF FWILLIIASV IGIIVYRLSV FIVFSAKLPK NINGTDPIQK YLTPQTATSI TASIISFIII MILNTIYEKV AIMITNFELP RTQTDYENSL TMKMFLFQFV NYYSSCFYIA FFKGKFVGYP GDPVYWLGKY RNEECDPGGC LLELTTQLTI IMGGKAIWNN IQEVLLPWIM NLIGRFHRVS GSEKITPRWE QDYHLQPMGK LGLFYEYLEM IIQFGFVTLF VASFPLAPLL ALVNNILEIR VDAWKLTTQF RRLVPEKAQD IGAWQPIMQG IAILAVVTNA MIIAFTSDMI PRLVYYWSFS VPPYGDHTSY TMEGYINNTL SIFKVADFKN KSKGNPYSDL GNHTTCRYRD FRYPPGHPQE YKHNIYYWHV IAAKLAFIIV MEHVIYSVKF FISYAIPDVS KRTKSKIQRE KYLTQKLLHE NHLKDMTKNM GVIAERMIEA VDNNLRPKSE //