ANO4_HUMAN
ID ANO4_HUMAN Reviewed; 955 AA.
AC Q32M45; Q8NAJ0; Q8NB39; Q8NB53;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Anoctamin-4;
DE AltName: Full=Transmembrane protein 16D;
GN Name=ANO4; Synonyms=TMEM16D;
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] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Prostate;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 IDENTIFICATION.
RX PubMed=12739008;
RA Katoh M., Katoh M.;
RT "FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome
RT 11q13, encodes the eight-transmembrane protein homologous to C12orf3,
RT C11orf25 and FLJ34272 gene products.";
RL Int. J. Oncol. 22:1375-1381(2003).
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 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 [7]
RP 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q8C5H1}.
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:Q8C5H1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664;
CC Evidence={ECO:0000250|UniProtKB:Q8C5H1};
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:Q8C5H1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38900;
CC Evidence={ECO:0000250|UniProtKB:Q8C5H1};
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:Q8C5H1};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573;
CC Evidence={ECO:0000250|UniProtKB:Q8C5H1};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22946059};
CC Multi-pass membrane protein {ECO:0000269|PubMed:22946059}. Note=Shows
CC an intracellular localization. {ECO:0000250|UniProtKB:Q8C5H1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q32M45-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q32M45-2; Sequence=VSP_025742;
CC Name=3;
CC IsoId=Q32M45-3; Sequence=VSP_025741, VSP_025743;
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=BAC03688.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK091540; BAC03688.1; ALT_INIT; mRNA.
DR EMBL; AK091591; BAC03704.1; -; mRNA.
DR EMBL; AK092596; BAC03924.1; -; mRNA.
DR EMBL; BC109308; AAI09309.1; -; mRNA.
DR CCDS; CCDS31884.1; -. [Q32M45-2]
DR CCDS; CCDS66445.1; -. [Q32M45-1]
DR RefSeq; NP_001273544.1; NM_001286615.1. [Q32M45-1]
DR RefSeq; NP_001273545.1; NM_001286616.1. [Q32M45-1]
DR RefSeq; NP_849148.2; NM_178826.3. [Q32M45-2]
DR RefSeq; XP_011536216.1; XM_011537914.2. [Q32M45-2]
DR RefSeq; XP_016874297.1; XM_017018808.1. [Q32M45-2]
DR RefSeq; XP_016874298.1; XM_017018809.1.
DR RefSeq; XP_016874299.1; XM_017018810.1. [Q32M45-2]
DR AlphaFoldDB; Q32M45; -.
DR SMR; Q32M45; -.
DR BioGRID; 125740; 19.
DR IntAct; Q32M45; 2.
DR STRING; 9606.ENSP00000376703; -.
DR TCDB; 1.A.17.1.29; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; Q32M45; 4 sites.
DR iPTMnet; Q32M45; -.
DR PhosphoSitePlus; Q32M45; -.
DR BioMuta; ANO4; -.
DR DMDM; 121942141; -.
DR jPOST; Q32M45; -.
DR MassIVE; Q32M45; -.
DR PaxDb; Q32M45; -.
DR PeptideAtlas; Q32M45; -.
DR PRIDE; Q32M45; -.
DR ProteomicsDB; 61589; -. [Q32M45-1]
DR ProteomicsDB; 61590; -. [Q32M45-2]
DR ProteomicsDB; 61591; -. [Q32M45-3]
DR Antibodypedia; 66428; 92 antibodies from 13 providers.
DR DNASU; 121601; -.
DR Ensembl; ENST00000392977.8; ENSP00000376703.3; ENSG00000151572.18. [Q32M45-1]
DR Ensembl; ENST00000392979.7; ENSP00000376705.3; ENSG00000151572.18. [Q32M45-2]
DR Ensembl; ENST00000570509.4; ENSP00000471431.2; ENSG00000262139.9.
DR Ensembl; ENST00000573650.8; ENSP00000469449.2; ENSG00000262139.9.
DR Ensembl; ENST00000575847.8; ENSP00000470039.2; ENSG00000262139.9.
DR GeneID; 121601; -.
DR KEGG; hsa:121601; -.
DR MANE-Select; ENST00000392977.8; ENSP00000376703.3; NM_001286615.2; NP_001273544.1.
DR UCSC; uc001thw.3; human. [Q32M45-1]
DR CTD; 121601; -.
DR DisGeNET; 121601; -.
DR GeneCards; ANO4; -.
DR HGNC; HGNC:23837; ANO4.
DR HPA; ENSG00000151572; Tissue enhanced (adrenal gland, brain, cervix, ovary, seminal vesicle).
DR MIM; 610111; gene.
DR neXtProt; NX_Q32M45; -.
DR OpenTargets; ENSG00000151572; -.
DR PharmGKB; PA164715582; -.
DR VEuPathDB; HostDB:ENSG00000151572; -.
DR eggNOG; KOG2514; Eukaryota.
DR GeneTree; ENSGT00940000158600; -.
DR HOGENOM; CLU_006685_1_3_1; -.
DR InParanoid; Q32M45; -.
DR OMA; SCVYAKX; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q32M45; -.
DR TreeFam; TF314265; -.
DR PathwayCommons; Q32M45; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q32M45; -.
DR BioGRID-ORCS; 121601; 12 hits in 1062 CRISPR screens.
DR ChiTaRS; ANO4; human.
DR GenomeRNAi; 121601; -.
DR Pharos; Q32M45; Tbio.
DR PRO; PR:Q32M45; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q32M45; protein.
DR Bgee; ENSG00000151572; Expressed in corpus callosum and 92 other tissues.
DR ExpressionAtlas; Q32M45; baseline and differential.
DR Genevisible; Q32M45; 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; IDA:UniProtKB.
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: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; IDA: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: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 2: Evidence at transcript 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_0000288650"
FT TOPO_DOM 1..352
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 374..424
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 446..505
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..547
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 569..595
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 596..616
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 617..715
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 716..736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 737..768
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 769..789
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 790..885
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 886..906
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 907..955
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 72..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..433
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025741"
FT VAR_SEQ 19..54
FT /note="EGGVDLQGYQLDMQILPDGPKSDVDFSEILNAIQEM -> V (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025742"
FT VAR_SEQ 466..512
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025743"
FT VARIANT 115
FT /note="G -> A (in dbSNP:rs34162417)"
FT /id="VAR_032453"
FT CONFLICT 209
FT /note="F -> L (in Ref. 1; BAC03704)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 955 AA; 111462 MW; 9A9348C61A4F20AF CRC64;
MEASSSGITN GKTKVFHPEG GVDLQGYQLD MQILPDGPKS DVDFSEILNA IQEMAKDVNI
LFDELEAVSS PCKDDDSLLH PGNLTSTSDD ASRLEAGGET VPERNKSNGL YFRDGKCRID
YILVYRKSNP QTEKREVFER NIRAEGLQME KESSLINSDI IFVKLHAPWE VLGRYAEQMN
VRMPFRRKIY YLPRRYKFMS RIDKQISRFR RWLPKKPMRL DKETLPDLEE NDCYTAPFSQ
QRIHHFIIHN KETFFNNATR SRIVHHILQR IKYEEGKNKI GLNRLLTNGS YEAAFPLHEG
SYRSKNSIRT HGAENHRHLL YECWASWGVW YKYQPLDLVR RYFGEKIGLY FAWLGWYTGM
LFPAAFIGLF VFLYGVTTLD HSQVSKEVCQ 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 RQEHGPERKI SFPQWEKDYN LQPMNAYGLF DEYLEMILQF
GFTTIFVAAF PLAPLLALLN NIIEIRLDAY KFVTQWRRPL ASRAKDIGIW YGILEGIGIL
SVITNAFVIA ITSDFIPRLV YAYKYGPCAG QGEAGQKCMV GYVNASLSVF RISDFENRSE
PESDGSEFSG TPLKYCRYRD YRDPPHSLVP YGYTLQFWHV LAARLAFIIV FEHLVFCIKH
LISYLIPDLP KDLRDRMRRE KYLIQEMMYE AELERLQKER KERKKNGKAH HNEWP
