ANO8_HUMAN
ID ANO8_HUMAN Reviewed; 1232 AA.
AC Q9HCE9; A6NIJ0;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Anoctamin-8;
DE AltName: Full=Transmembrane protein 16H;
GN Name=ANO8; Synonyms=KIAA1623, TMEM16H;
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).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=15647853;
RA Katoh M., Katoh M.;
RT "Identification and characterization of TMEM16H gene in silico.";
RL Int. J. Mol. Med. 15:353-358(2005).
RN [6]
RP ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY, AND SUBCELLULAR
RP 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 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 [8]
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 [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 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 [11]
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 [12]
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).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP PHOSPHORYLATION AT SER-801.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
CC -!- FUNCTION: Does not exhibit calcium-activated chloride channel (CaCC)
CC activity.
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=2;
CC Name=1;
CC IsoId=Q9HCE9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HCE9-2; Sequence=VSP_020351, VSP_020352;
CC -!- TISSUE SPECIFICITY: Expressed in embryonic stem cells, fetal brain and
CC neural tissues. {ECO:0000269|PubMed:15647853}.
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=BAB13449.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB046843; BAB13449.2; ALT_INIT; mRNA.
DR EMBL; AC010463; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84595.1; -; Genomic_DNA.
DR CCDS; CCDS32949.1; -. [Q9HCE9-1]
DR RefSeq; NP_066010.1; NM_020959.2. [Q9HCE9-1]
DR RefSeq; XP_016882537.1; XM_017027048.1. [Q9HCE9-2]
DR AlphaFoldDB; Q9HCE9; -.
DR SMR; Q9HCE9; -.
DR BioGRID; 121742; 9.
DR IntAct; Q9HCE9; 2.
DR MINT; Q9HCE9; -.
DR STRING; 9606.ENSP00000159087; -.
DR iPTMnet; Q9HCE9; -.
DR PhosphoSitePlus; Q9HCE9; -.
DR BioMuta; ANO8; -.
DR DMDM; 114152287; -.
DR EPD; Q9HCE9; -.
DR jPOST; Q9HCE9; -.
DR MassIVE; Q9HCE9; -.
DR MaxQB; Q9HCE9; -.
DR PaxDb; Q9HCE9; -.
DR PeptideAtlas; Q9HCE9; -.
DR PRIDE; Q9HCE9; -.
DR ProteomicsDB; 81695; -. [Q9HCE9-1]
DR ProteomicsDB; 81696; -. [Q9HCE9-2]
DR Antibodypedia; 43758; 24 antibodies from 14 providers.
DR DNASU; 57719; -.
DR Ensembl; ENST00000159087.7; ENSP00000159087.4; ENSG00000074855.11. [Q9HCE9-1]
DR GeneID; 57719; -.
DR KEGG; hsa:57719; -.
DR MANE-Select; ENST00000159087.7; ENSP00000159087.4; NM_020959.3; NP_066010.1.
DR UCSC; uc002ngf.2; human. [Q9HCE9-1]
DR CTD; 57719; -.
DR DisGeNET; 57719; -.
DR GeneCards; ANO8; -.
DR HGNC; HGNC:29329; ANO8.
DR HPA; ENSG00000074855; Low tissue specificity.
DR MIM; 610216; gene.
DR neXtProt; NX_Q9HCE9; -.
DR OpenTargets; ENSG00000074855; -.
DR PharmGKB; PA164715790; -.
DR VEuPathDB; HostDB:ENSG00000074855; -.
DR eggNOG; KOG2513; Eukaryota.
DR GeneTree; ENSGT00940000157019; -.
DR HOGENOM; CLU_006685_2_1_1; -.
DR InParanoid; Q9HCE9; -.
DR OMA; YWMENLR; -.
DR OrthoDB; 1263362at2759; -.
DR PhylomeDB; Q9HCE9; -.
DR TreeFam; TF314265; -.
DR PathwayCommons; Q9HCE9; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q9HCE9; -.
DR BioGRID-ORCS; 57719; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; ANO8; human.
DR GenomeRNAi; 57719; -.
DR Pharos; Q9HCE9; Tbio.
DR PRO; PR:Q9HCE9; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9HCE9; protein.
DR Bgee; ENSG00000074855; Expressed in cortical plate and 97 other tissues.
DR ExpressionAtlas; Q9HCE9; baseline and differential.
DR Genevisible; Q9HCE9; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IMP:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IMP:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR InterPro; IPR007632; Anoctamin.
DR InterPro; IPR031289; Anoctamin-8.
DR PANTHER; PTHR12308; PTHR12308; 1.
DR PANTHER; PTHR12308:SF33; PTHR12308:SF33; 1.
DR Pfam; PF04547; Anoctamin; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Membrane; Methylation;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..1232
FT /note="Anoctamin-8"
FT /id="PRO_0000249003"
FT TOPO_DOM 2..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 303..356
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 378..400
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 401..421
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 422..437
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..750
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 751..771
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 772..807
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 808..828
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 829..841
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 842..862
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 863..1232
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 681..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 888..970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 997..1152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1174..1232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 557..577
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..605
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 606..623
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..728
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 888..934
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1031..1047
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1073..1088
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1092..1106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1127..1148
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1176..1223
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PB70"
FT MOD_RES 669
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PB70"
FT MOD_RES 801
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 1020
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q6PB70"
FT MOD_RES 1020
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q6PB70"
FT VAR_SEQ 1112..1114
FT /note="TAL -> HKL (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_020351"
FT VAR_SEQ 1115..1232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_020352"
SQ SEQUENCE 1232 AA; 136034 MW; 1802BC3544A9234C CRC64;
MAEAASGAGG TSLEGERGKR PPPEGEPAAP ASGVLDKLFG KRLLQAGRYL VSHKAWMKTV
PTENCDVLMT FPDTTDDHTL LWLLNHIRVG IPELIVQVRH HRHTRAYAFF VTATYESLLR
GADELGLRKA VKAEFGGGTR GFSCEEDFIY ENVESELRFF TSQERQSIIR FWLQNLRAKQ
GEALHNVRFL EDQPIIPELA ARGIIQQVFP VHEQRILNRL MKSWVQAVCE NQPLDDICDY
FGVKIAMYFA WLGFYTSAMV YPAVFGSVLY TFTEADQTSR DVSCVVFALF NVIWSTLFLE
EWKRRGAELA YKWGTLDSPG EAVEEPRPQF RGVRRISPIT RAEEFYYPPW KRLLFQLLVS
LPLCLACLVC VFLLMLGCFQ LQELVLSVKG LPRLARFLPK VMLALLVSVS AEGYKKLAIW
LNDMENYRLE SAYEKHLIIK VVLFQFVNSY LSLFYIGFYL KDMERLKEML ATLLITRQFL
QNVREVLQPH LYRRLGRGEL GLRAVWELAR ALLGLLSLRR PAPRRLEPQA DEGGGGGSGG
GGRRCLSGGC GAPEEEEEAA LVERRRAGEG GEEGDGPPGG KEEDEDDEEE EDEEEEEDEE
EGEEGGLLDC GLRLKKVSFA ERGAGRRRPG PSPEALLEEG SPTMVEKGLE PGVFTLAEED
DEAEGAPGSP EREPPAILFR RAGGEGRDQG PDGGPDPEPG SNSDSTRRQR RQNRSSWIDP
PEEEHSPQLT QAELESCMKK YEDTFQDYQE MFVQFGYVVL FSSAFPLAAL CALVNNLIEI
RSDAFKLCTG LQRPFGQRVE SIGQWQKVME AMGVLAIVVN CYLIGQCGQL QRLFPWLSPE
AAIVSVVVLE HFALLLKYLI HVAIPDIPGW VAEEMAKLEY QRREAFKRHE RQAQHRYQQQ
QRRRREEEER QRHAEHHARR EHDSGGREEA RAEGSGLDPA TSSEKASAKA KGSTAGGHGP
ERPKRPGSLL APNNVMKLKQ IIPLQGKFLS SGATSSLAAA GAGATTRPPP AQSPTGSDTR
LPAFLSFKFL KSPETRRDSE RSHSPPKAFH AGKLFPFGGT RAEPGSNGAG GQARPDGTPS
SGSSRVQRSG PVDEALAEEL EAPRPEEEGS GTALAPVGAP ALRTRRSRSP APPPPMPLPR
PPTPPAGCWQ WDGPWGCGGE GAAPRQALAA AECPPCAMAG PPPAPQPLPG DASFYSLPPP
PLPPTSDPLE TPAPSPSPSP SPQAVCWPSG WH
