ANO3_HUMAN
ID ANO3_HUMAN Reviewed; 981 AA.
AC Q9BYT9; B7Z3F5;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Anoctamin-3;
DE AltName: Full=Transmembrane protein 16C;
GN Name=ANO3; Synonyms=C11orf25, TMEM16C; ORFNames=GENX-3947;
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 [MRNA] (ISOFORM 1).
RA Rosier M.F., Toselli E., Segurens-Soury B., Auffray C., Devignes M.D.;
RT "Predominant brain expression and full-length characterization of a novel
RT human 6.6-Kb transcript mapping at 11p14 in the telomeric part of WAGR
RT locus.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
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 [5]
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 [6]
RP TISSUE SPECIFICITY, AND VARIANTS DYT24 CYS-490; TRP-494; GLY-685 AND
RP ASN-862.
RX PubMed=23200863; DOI=10.1016/j.ajhg.2012.10.024;
RA Charlesworth G., Plagnol V., Holmstroem K.M., Bras J., Sheerin U.M.,
RA Preza E., Rubio-Agusti I., Ryten M., Schneider S.A., Stamelou M.,
RA Trabzuni D., Abramov A.Y., Bhatia K.P., Wood N.W.;
RT "Mutations in ANO3 cause dominant craniocervical dystonia: ion channel
RT implicated in pathogenesis.";
RL Am. J. Hum. Genet. 91:1041-1050(2012).
RN [7]
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 [8]
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).
CC -!- FUNCTION: Has calcium-dependent phospholipid scramblase activity;
CC scrambles phosphatidylcholine and galactosylceramide (By similarity).
CC Seems to act as potassium channel regulator and may inhibit pain
CC signaling; can facilitate KCNT1/Slack channel activity by promoting its
CC full single-channel conductance at very low sodium concentrations and
CC by increasing its sodium sensitivity (By similarity). Does not exhibit
CC calcium-activated chloride channel (CaCC) activity (PubMed:21984732).
CC {ECO:0000250|UniProtKB:A2AHL1, ECO:0000303|PubMed:21984732}.
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:A2AHL1};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573;
CC Evidence={ECO:0000250|UniProtKB:A2AHL1};
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:A2AHL1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38900;
CC Evidence={ECO:0000250|UniProtKB:A2AHL1};
CC -!- SUBUNIT: Interacts with KCNT1/Slack. {ECO:0000250|UniProtKB:A2AHL1}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Note=Shows an intracellular localization.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BYT9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYT9-2; Sequence=VSP_056893;
CC -!- TISSUE SPECIFICITY: Highly expressed in the forebrain striatum.
CC {ECO:0000269|PubMed:23200863}.
CC -!- DISEASE: Dystonia 24 (DYT24) [MIM:615034]: A form of dystonia, a
CC disorder defined by the presence of sustained involuntary muscle
CC contraction, often leading to abnormal postures. DYT24 is an autosomal
CC dominant focal dystonia affecting the neck, laryngeal muscles, and
CC muscles of the upper limbs. {ECO:0000269|PubMed:23200863}. 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 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. {ECO:0000305}.
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DR EMBL; AJ300461; CAC32454.1; -; mRNA.
DR EMBL; AK295816; BAH12191.1; -; mRNA.
DR EMBL; AC021698; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC036114; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079064; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC083755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC099687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS31447.1; -. [Q9BYT9-1]
DR CCDS; CCDS81557.1; -. [Q9BYT9-2]
DR RefSeq; NP_001300655.1; NM_001313726.1.
DR RefSeq; NP_001300656.1; NM_001313727.1. [Q9BYT9-2]
DR RefSeq; NP_113606.2; NM_031418.3. [Q9BYT9-1]
DR RefSeq; XP_016873607.1; XM_017018118.1. [Q9BYT9-2]
DR AlphaFoldDB; Q9BYT9; -.
DR SMR; Q9BYT9; -.
DR BioGRID; 122027; 8.
DR IntAct; Q9BYT9; 8.
DR STRING; 9606.ENSP00000256737; -.
DR TCDB; 1.A.17.1.20; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; Q9BYT9; 4 sites.
DR iPTMnet; Q9BYT9; -.
DR PhosphoSitePlus; Q9BYT9; -.
DR BioMuta; ANO3; -.
DR DMDM; 296434396; -.
DR MassIVE; Q9BYT9; -.
DR PaxDb; Q9BYT9; -.
DR PeptideAtlas; Q9BYT9; -.
DR PRIDE; Q9BYT9; -.
DR ProteomicsDB; 6516; -.
DR ProteomicsDB; 79708; -. [Q9BYT9-1]
DR Antibodypedia; 25359; 116 antibodies from 25 providers.
DR DNASU; 63982; -.
DR Ensembl; ENST00000256737.8; ENSP00000256737.3; ENSG00000134343.14. [Q9BYT9-1]
DR Ensembl; ENST00000531568.1; ENSP00000432394.1; ENSG00000134343.14. [Q9BYT9-2]
DR GeneID; 63982; -.
DR KEGG; hsa:63982; -.
DR MANE-Select; ENST00000256737.8; ENSP00000256737.3; NM_031418.4; NP_113606.2.
DR UCSC; uc001mqt.5; human. [Q9BYT9-1]
DR CTD; 63982; -.
DR DisGeNET; 63982; -.
DR GeneCards; ANO3; -.
DR HGNC; HGNC:14004; ANO3.
DR HPA; ENSG00000134343; Group enriched (brain, epididymis).
DR MalaCards; ANO3; -.
DR MIM; 610110; gene.
DR MIM; 615034; phenotype.
DR neXtProt; NX_Q9BYT9; -.
DR OpenTargets; ENSG00000134343; -.
DR Orphanet; 420485; Cranio-cervical dystonia with laryngeal and upper-limb involvement.
DR PharmGKB; PA25489; -.
DR VEuPathDB; HostDB:ENSG00000134343; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000156257; -.
DR HOGENOM; CLU_006685_1_3_1; -.
DR InParanoid; Q9BYT9; -.
DR OMA; PCANHVK; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q9BYT9; -.
DR TreeFam; TF314265; -.
DR PathwayCommons; Q9BYT9; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q9BYT9; -.
DR BioGRID-ORCS; 63982; 21 hits in 1068 CRISPR screens.
DR ChiTaRS; ANO3; human.
DR GenomeRNAi; 63982; -.
DR Pharos; Q9BYT9; Tbio.
DR PRO; PR:Q9BYT9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BYT9; protein.
DR Bgee; ENSG00000134343; Expressed in corpus epididymis and 132 other tissues.
DR ExpressionAtlas; Q9BYT9; baseline and differential.
DR Genevisible; Q9BYT9; HS.
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:0005229; F:intracellular calcium activated chloride channel activity; TAS:Reactome.
DR GO; GO:0017128; F:phospholipid scramblase activity; IEA:Ensembl.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0061591; P:calcium activated galactosylceramide scrambling; IEA:Ensembl.
DR GO; GO:0061590; P:calcium activated phosphatidylcholine scrambling; IEA:Ensembl.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0050982; P:detection of mechanical stimulus; IEA:Ensembl.
DR GO; GO:0016048; P:detection of temperature stimulus; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
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; Disease variant; Dystonia;
KW Glycoprotein; Lipid transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..981
FT /note="Anoctamin-3"
FT /id="PRO_0000072565"
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..33
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 1..146
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056893"
FT VARIANT 490
FT /note="W -> C (in DYT24; dbSNP:rs1565132917)"
FT /evidence="ECO:0000269|PubMed:23200863"
FT /id="VAR_069732"
FT VARIANT 494
FT /note="R -> W (in DYT24; dbSNP:rs587776922)"
FT /evidence="ECO:0000269|PubMed:23200863"
FT /id="VAR_069733"
FT VARIANT 685
FT /note="S -> G (in DYT24; dbSNP:rs587776923)"
FT /evidence="ECO:0000269|PubMed:23200863"
FT /id="VAR_069734"
FT VARIANT 781
FT /note="L -> V (in dbSNP:rs11825056)"
FT /id="VAR_057287"
FT VARIANT 862
FT /note="K -> N (in DYT24; dbSNP:rs1277790116)"
FT /evidence="ECO:0000269|PubMed:23200863"
FT /id="VAR_069735"
FT CONFLICT 162
FT /note="K -> R (in Ref. 1; CAC32454)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="Q -> P (in Ref. 1; CAC32454)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="N -> D (in Ref. 1; CAC32454)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 981 AA; 114657 MW; FC7449D2D4810290 CRC64;
MVHHSGSIQS FKQQKGMNIS KSEITKETSL KPSRRSLPCL AQSYAYSKSL SQSTSLFQST
ESESQAPTSI TLISTDKAEQ VNTEENKNDS VLRCSFADLS DFCLALGKDK DYTDESEHAT
YDRSRLINDF VIKDKSEFKT KLSKNDMNYI ASSGPLFKDG KKRIDYILVY RKTNIQYDKR
NTFEKNLRAE GLMLEKEPAI ASPDIMFIKI HIPWDTLCKY AERLNIRMPF RKKCYYTDGR
SKSMGRMQTY FRRIKNWMAQ NPMVLDKSAF PDLEESDCYT GPFSRARIHH FIINNKDTFF
SNATRSRIVY HMLERTKYEN GISKVGIRKL INNGSYIAAF PPHEGAYKSS QPIKTHGPQN
NRHLLYERWA RWGMWYKHQP LDLIRLYFGE KIGLYFAWLG WYTGMLIPAA IVGLCVFFYG
LFTMNNSQVS QEICKATEVF MCPLCDKNCS LQRLNDSCIY AKVTYLFDNG GTVFFAIFMA
IWATVFLEFW KRRRSILTYT WDLIEWEEEE ETLRPQFEAK YYKMEIVNPI TGKPEPHQPS
SDKVTRLLVS VSGIFFMISL VITAVFGVVV YRLVVMEQFA SFKWNFIKQY WQFATSAAAV
CINFIIIMLL NLAYEKIAYL LTNLEYPRTE SEWENSFALK MFLFQFVNLN SSIFYIAFFL
GRFVGHPGKY NKLFDRWRLE ECHPSGCLID LCLQMGVIMF LKQIWNNFME LGYPLIQNWW
SRHKIKRGIH DASIPQWEND WNLQPMNLHG LMDEYLEMVL QFGFTTIFVA AFPLAPLLAL
LNNIIEIRLD AYKFVTQWRR PLPARATDIG IWLGILEGIG ILAVITNAFV IAITSDYIPR
FVYEYKYGPC ANHVEPSENC LKGYVNNSLS FFDLSELGMG KSGYCRYRDY RGPPWSSKPY
EFTLQYWHIL AARLAFIIVF EHLVFGIKSF IAYLIPDVPK GLHDRIRREK YLVQEMMYEA
ELEHLQQQRR KSGQPVHHEW P
