ANO4_MOUSE
ID ANO4_MOUSE Reviewed; 955 AA.
AC Q8C5H1; Q8CA37;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Anoctamin-4 {ECO:0000250|UniProtKB:Q32M45};
DE AltName: Full=Transmembrane protein 16D {ECO:0000250|UniProtKB:Q32M45};
GN Name=Ano4 {ECO:0000250|UniProtKB:Q32M45};
GN Synonyms=Tmem16d {ECO:0000312|MGI:MGI:2443344};
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] {ECO:0000305, ECO:0000312|EMBL:BAC37238.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC37238.1};
RC TISSUE=Cerebellum {ECO:0000312|EMBL:BAC37238.1}, and
RC Spinal cord {ECO:0000312|EMBL:BAC30429.1};
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 [2]
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 [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 ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY, AND SUBCELLULAR
RP 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 [5]
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 [6]
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).
CC -!- FUNCTION: Has calcium-dependent phospholipid scramblase activity;
CC scrambles phosphatidylserine, phosphatidylcholine and
CC galactosylceramide (PubMed:23532839). Does not exhibit calcium-
CC activated chloride channel (CaCC) activity (PubMed:22075693).
CC {ECO:0000269|PubMed:22075693, ECO:0000269|PubMed:23532839}.
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 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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q32M45};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q32M45}. Note=Shows
CC an intracellular localization according to PubMed:22075693.
CC {ECO:0000269|PubMed:22075693}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8C5H1-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:16141072};
CC IsoId=Q8C5H1-2; Sequence=VSP_052962, VSP_052963;
CC Name=3 {ECO:0000269|PubMed:16141072};
CC IsoId=Q8C5H1-3; Sequence=VSP_052960, VSP_052961;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in neuronal tissues.
CC Expressed at low levels in ovary, uterus, heart and brain.
CC {ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:23532839}.
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 -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the anoctamin family.
CC {ECO:0000250|UniProtKB:Q32M45}.
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DR EMBL; AK039728; BAC30429.1; -; mRNA.
DR EMBL; AK078364; BAC37238.1; -; mRNA.
DR EMBL; AC124504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS24114.2; -. [Q8C5H1-1]
DR RefSeq; NP_001264117.1; NM_001277188.1. [Q8C5H1-1]
DR RefSeq; XP_006513821.1; XM_006513758.3.
DR AlphaFoldDB; Q8C5H1; -.
DR SMR; Q8C5H1; -.
DR SwissLipids; SLP:000000374; -.
DR GlyGen; Q8C5H1; 3 sites.
DR PhosphoSitePlus; Q8C5H1; -.
DR MaxQB; Q8C5H1; -.
DR PaxDb; Q8C5H1; -.
DR PRIDE; Q8C5H1; -.
DR ProteomicsDB; 282110; -. [Q8C5H1-1]
DR ProteomicsDB; 282111; -. [Q8C5H1-2]
DR ProteomicsDB; 282112; -. [Q8C5H1-3]
DR Antibodypedia; 66428; 92 antibodies from 13 providers.
DR DNASU; 320091; -.
DR Ensembl; ENSMUST00000181976; ENSMUSP00000138792; ENSMUSG00000035189. [Q8C5H1-3]
DR Ensembl; ENSMUST00000182341; ENSMUSP00000138193; ENSMUSG00000035189. [Q8C5H1-1]
DR GeneID; 320091; -.
DR KEGG; mmu:320091; -.
DR UCSC; uc007gsa.1; mouse. [Q8C5H1-1]
DR UCSC; uc007gsb.1; mouse. [Q8C5H1-2]
DR UCSC; uc007gsc.1; mouse. [Q8C5H1-3]
DR CTD; 121601; -.
DR MGI; MGI:2443344; Ano4.
DR VEuPathDB; HostDB:ENSMUSG00000035189; -.
DR GeneTree; ENSGT00940000158600; -.
DR InParanoid; Q8C5H1; -.
DR OMA; SCVYAKX; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q8C5H1; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 320091; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Ano4; mouse.
DR PRO; PR:Q8C5H1; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8C5H1; protein.
DR Bgee; ENSMUSG00000035189; Expressed in otolith organ and 116 other tissues.
DR ExpressionAtlas; Q8C5H1; baseline and differential.
DR Genevisible; Q8C5H1; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:0061589; P:calcium activated phosphatidylserine scrambling; IDA:MGI.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0006821; P:chloride transport; 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; IPR031293; Anoctamin-4.
DR PANTHER; PTHR12308; PTHR12308; 1.
DR PANTHER; PTHR12308:SF28; PTHR12308:SF28; 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..955
FT /note="Anoctamin-4"
FT /id="PRO_0000353190"
FT TOPO_DOM 1..352
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 374..424
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 446..505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 569..595
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 596..616
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 617..715
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 716..736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 737..768
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 769..789
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 790..885
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 886..906
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 907..955
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 73..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..94
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 544
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 824
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 837
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 245
FT /note="H -> Q (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052960"
FT VAR_SEQ 246..955
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052961"
FT VAR_SEQ 438..439
FT /note="AT -> GK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052962"
FT VAR_SEQ 440..955
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052963"
FT CONFLICT 214
FT /note="P -> H (in Ref. 1; BAC30429)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 955 AA; 111544 MW; DE3F0B931B21FB6A CRC64;
MEASSSGITN GKNKVFHAEG GLDLQSHQLD MQILPDGPKS DVDFSEILNA IQEMAKDVNI
LFDELEAVNS PCKDDDSLLH PGNLTSTSED TSRLEAGGET VRERNKSNGL YFRDGKCRID
YILVYRKSNP QTEKREVFER NIRAEGLQME KESSLINSDI IFVKLHAPWE VLGRYAEQMN
VRMPFRRKIY YLPRRYKFMS RIDKQISRFR RWLPKKPMRL DKETLPDLEE NDCYTAPFSQ
QRIHHFIIHN KDTFFNNATR SRIVHHILQR IKYEEGKNKI GLNRLLTNGS YEAAFPLHEG
SYRSKNSIKT HGAVNHRHLL YECWASWGVW YKYQPLDLVR RYFGEKIGLY FAWLGWYTGM
LFPAAFIGLF VFLYGVTTLD HCQVSKEVCQ ATDIIMCPVC DKYCPFMRLS DSCVYAKVTH
LFDNGATVFF AVFMAVWATV FLEFWKRRRA VIAYDWDLID WEEEEEEIRP QFEAKYSKKE
RMNPISGKPE PYQAFTDKCS RLIVSASGIF FMICVVIAAV FGIVIYRVVT VSTFAAFKWA
LIRNNSQVAT TGTAVCINFC IIMLLNVLYE KVALLLTNLE QPRTESEWEN SFTLKMFLFQ
FVNLNSSTFY IAFFLGRFTG HPGAYLRLIN RWRLEECHPS GCLIDLCMQM GIIMVLKQTW
NNFMELGYPL IQNWWTRRKV RQEHGTERKI NFPQWEKDYN LQPMNAYGLF DEYLEMILQF
GFTTIFVAAF PLAPLLALLN NIIEIRLDAY KFVTQWRRPL ASRAKDIGIW YGILEGIGIL
SVITNAFVIA ITSDFIPRLV YAYKYGPCAG QGEAGQKCMV GYVNASLSVF RISDFENRSE
PESDGSEFSG TPLKYCRYRD YRDPPHSLAP YGYTLQFWHV LAARLAFIIV FEHLVFCIKH
LISYLIPDLP KDLRDRMRRE KYLIQEMMYE AELERLQKER KERKKNGKAH HNEWP
