ANO9_HUMAN
ID ANO9_HUMAN Reviewed; 782 AA.
AC A1A5B4; B3KUC4; B4E134; Q8TEN4;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2015, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Anoctamin-9;
DE AltName: Full=Transmembrane protein 16J;
DE AltName: Full=Tumor protein p53-inducible protein 5;
DE AltName: Full=p53-induced gene 5 protein;
GN Name=ANO9; Synonyms=PIG5, TMEM16J, TP53I5;
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 MRNA] (ISOFORM 1), AND VARIANTS VAL-391
RP AND ARG-399.
RC TISSUE=Spleen;
RX PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen. II. The
RT complete sequences of 81 cDNA clones.";
RL DNA Res. 10:49-57(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS
RP VAL-391 AND ARG-399.
RC TISSUE=Salivary gland, and Thymus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-391
RP AND ARG-399.
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 [5]
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 [6]
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 [7]
RP ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY.
RX PubMed=22178883; DOI=10.1159/000335765;
RA Ousingsawat J., Kongsuphol P., Schreiber R., Kunzelmann K.;
RT "CFTR and TMEM16A are separate but functionally related Cl-channels.";
RL Cell. Physiol. Biochem. 28:715-724(2011).
RN [8]
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 [9]
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 [10]
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 [11]
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).
CC -!- FUNCTION: Has calcium-dependent phospholipid scramblase activity;
CC scrambles phosphatidylserine, phosphatidylcholine and
CC galactosylceramide (By similarity). Does not exhibit calcium-activated
CC chloride channel (CaCC) activity (PubMed:22178883). Can inhibit the
CC activity of ANO1 (PubMed:20056604, PubMed:22946059).
CC {ECO:0000250|UniProtKB:P86044, ECO:0000269|PubMed:20056604,
CC ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:22946059}.
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:P86044};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664;
CC Evidence={ECO:0000250|UniProtKB:P86044};
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:P86044};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38900;
CC Evidence={ECO:0000250|UniProtKB:P86044};
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:P86044};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573;
CC Evidence={ECO:0000250|UniProtKB:P86044};
CC -!- INTERACTION:
CC A1A5B4; Q12959: DLG1; NbExp=2; IntAct=EBI-3843564, EBI-357481;
CC A1A5B4; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-3843564, EBI-742388;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20056604,
CC ECO:0000269|PubMed:22946059}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:22946059}. Note=Shows
CC predominantly an intracellular localization with a weak expression in
CC the cell membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A1A5B4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A1A5B4-2; Sequence=VSP_036489, VSP_036492;
CC Name=3;
CC IsoId=A1A5B4-3; Sequence=VSP_036490, VSP_036491;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84914.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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; AK074088; BAB84914.1; ALT_SEQ; mRNA.
DR EMBL; AK096874; BAG53386.1; -; mRNA.
DR EMBL; AK303642; BAG64646.1; -; mRNA.
DR EMBL; AC138230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC128557; AAI28558.1; -; mRNA.
DR CCDS; CCDS31326.1; -. [A1A5B4-1]
DR RefSeq; NP_001012302.2; NM_001012302.2. [A1A5B4-1]
DR RefSeq; XP_011518355.1; XM_011520053.2. [A1A5B4-2]
DR AlphaFoldDB; A1A5B4; -.
DR SMR; A1A5B4; -.
DR BioGRID; 130747; 4.
DR IntAct; A1A5B4; 2.
DR MINT; A1A5B4; -.
DR STRING; 9606.ENSP00000332788; -.
DR TCDB; 1.A.17.1.5; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; A1A5B4; 4 sites.
DR iPTMnet; A1A5B4; -.
DR PhosphoSitePlus; A1A5B4; -.
DR BioMuta; ANO9; -.
DR EPD; A1A5B4; -.
DR jPOST; A1A5B4; -.
DR MassIVE; A1A5B4; -.
DR PaxDb; A1A5B4; -.
DR PeptideAtlas; A1A5B4; -.
DR PRIDE; A1A5B4; -.
DR ProteomicsDB; 110; -. [A1A5B4-1]
DR ProteomicsDB; 111; -. [A1A5B4-2]
DR ProteomicsDB; 112; -. [A1A5B4-3]
DR Antibodypedia; 58906; 75 antibodies from 20 providers.
DR DNASU; 338440; -.
DR Ensembl; ENST00000332826.7; ENSP00000332788.6; ENSG00000185101.13. [A1A5B4-1]
DR GeneID; 338440; -.
DR KEGG; hsa:338440; -.
DR MANE-Select; ENST00000332826.7; ENSP00000332788.6; NM_001012302.3; NP_001012302.2.
DR UCSC; uc001lpi.3; human. [A1A5B4-1]
DR CTD; 338440; -.
DR DisGeNET; 338440; -.
DR GeneCards; ANO9; -.
DR HGNC; HGNC:20679; ANO9.
DR HPA; ENSG00000185101; Tissue enhanced (intestine, skin).
DR neXtProt; NX_A1A5B4; -.
DR OpenTargets; ENSG00000185101; -.
DR PharmGKB; PA164715791; -.
DR VEuPathDB; HostDB:ENSG00000185101; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000158300; -.
DR HOGENOM; CLU_006685_3_1_1; -.
DR InParanoid; A1A5B4; -.
DR OMA; MAIWTTL; -.
DR OrthoDB; 1263362at2759; -.
DR TreeFam; TF314265; -.
DR PathwayCommons; A1A5B4; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; A1A5B4; -.
DR BioGRID-ORCS; 338440; 12 hits in 1084 CRISPR screens.
DR ChiTaRS; ANO9; human.
DR GenomeRNAi; 338440; -.
DR Pharos; A1A5B4; Tbio.
DR PRO; PR:A1A5B4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; A1A5B4; protein.
DR Bgee; ENSG00000185101; Expressed in mucosa of transverse colon and 126 other tissues.
DR Genevisible; A1A5B4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IBA:GO_Central.
DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IMP:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; IEA:Ensembl.
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:0061589; P:calcium activated phosphatidylserine scrambling; IEA:Ensembl.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0006821; P:chloride transport; IMP:UniProtKB.
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:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:1902939; P:negative regulation of intracellular calcium activated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR InterPro; IPR007632; Anoctamin.
DR InterPro; IPR031290; Anoctamin-9.
DR PANTHER; PTHR12308; PTHR12308; 1.
DR PANTHER; PTHR12308:SF37; PTHR12308:SF37; 1.
DR Pfam; PF04547; Anoctamin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Lipid metabolism;
KW Lipid transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..782
FT /note="Anoctamin-9"
FT /id="PRO_0000289329"
FT TOPO_DOM 1..198
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 220..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 353..373
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 395..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..444
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 445..552
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 553..573
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 574..604
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 605..625
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 626..703
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 704..724
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 725..782
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 756..782
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 652
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 674
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 690
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..299
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036489"
FT VAR_SEQ 156..186
FT /note="GEGRLKKTWARWRHMFREQPVDEIRNYFGEK -> VRGGPAWRGPWGGTLGW
FT GLSLSVTRARGRDA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036490"
FT VAR_SEQ 187..782
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036491"
FT VAR_SEQ 300..305
FT /note="VWDEEQ -> MPAVSE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036492"
FT VARIANT 93
FT /note="L -> F (in dbSNP:rs7395065)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_054621"
FT VARIANT 391
FT /note="I -> V (in dbSNP:rs10794324)"
FT /evidence="ECO:0000269|PubMed:12693554,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_032617"
FT VARIANT 399
FT /note="C -> R (in dbSNP:rs10794323)"
FT /evidence="ECO:0000269|PubMed:12693554,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_032618"
SQ SEQUENCE 782 AA; 90333 MW; 6A359B63DD92AFF7 CRC64;
MQGEESLRIL VEPEGDSFPL MEISTCETEA SEQWDYVLVA QRHTQRDPRQ ARQQQFLEEL
RRKGFHIKVI RDQKQVFFGI RADNSVFGLY RTLLLEPEGP APHAELAAPT TIPVTTSLRI
RIVNFVVMNN KTSAGETFED LMKDGVFEAR FPLHKGEGRL KKTWARWRHM FREQPVDEIR
NYFGEKVALY FVWLGWYTYM LVPAALTGLL VFLSGFSLFE ASQISKEICE AHDILMCPLG
DHSRRYQRLS ETCTFAKLTH LFDNDGTVVF AIFMALWATV FLEIWKRQRA RVVLHWDLYV
WDEEQEEMAL QLINCPDYKL RPYQHSYLRS TVILVLTLLM ICLMIGMAHV LVVYRVLASA
LFSSSAVPFL EEQVTTAVVV TGALVHYVTI IIMTKINRCV ALKLCDFEMP RTFSERESRF
TIRFFTLQFF THFSSLIYIA FILGRINGHP GKSTRLAGLW KLEECHASGC MMDLFVQMAI
IMGLKQTLSN CVEYLVPWVT HKCRSLRASE SGHLPRDPEL RDWRRNYLLN PVNTFSLFDE
FMEMMIQYGF TTIFVAAFPL APLLALFSNL VEIRLDAIKM VWLQRRLVPR KAKDIGTWLQ
VLETIGVLAV IANGMVIAFT SEFIPRVVYK YRYSPCLKEG NSTVDCLKGY VNHSLSVFHT
KDFQDPDGIE GSENVTLCRY RDYRNPPDYN FSEQFWFLLA IRLAFVILFE HVALCIKLIA
AWFVPDIPQS VKNKVLEVKY QRLREKMWHG RQRLGGVGAG SRPPMPAHPT PASIFSARST
DV
