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Q5XXA6 (ANO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Anoctamin-1
Alternative name(s):
Discovered on gastrointestinal stromal tumors protein 1
Oral cancer overexpressed protein 2
Transmembrane protein 16A
Tumor-amplified and overexpressed sequence 2
Gene names
Name:ANO1
Synonyms:DOG1, ORAOV2, TAOS2, TMEM16A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length986 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-activated chloride channel (CaCC) which plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. Ref.7 Ref.11 Ref.15 Ref.17

Enzyme regulation

ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Ref.11

Subunit structure

Homodimer. Interacts with CFTR. Ref.11 Ref.12

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasm. Note: Cytoplasmic localization seen in neoplastic cells of head and neck squamous cell carcinoma (HNSCC) tumors. Ref.5 Ref.6 Ref.7 Ref.11 Ref.15 Ref.17

Tissue specificity

Broadly expressed with higher levels in liver, skeletal muscle and gastrointestinal muscles. Ref.1 Ref.5

Domain

The region spanning the fifth and sixth transmembrane domains probably forms the pore-forming region By similarity.

Miscellaneous

The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.

Sequence similarities

Belongs to the anoctamin family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5XXA6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q5XXA6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-116: Missing.
     448-451: Missing.
     476-501: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q5XXA6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.
     29-36: GYLPSEGT → MLTRPSQV
     448-451: Missing.
     476-501: Missing.
     651-700: CAPGGCLMEL...RYLKLKQQSP → VTEILFISGS...SFLLETFLFP
     701-986: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 986986Anoctamin-1
PRO_0000288435

Regions

Topological domain1 – 333333Cytoplasmic Potential
Transmembrane334 – 35421Helical; Potential
Topological domain355 – 40248Extracellular Potential
Transmembrane403 – 42321Helical; Potential
Topological domain424 – 51996Cytoplasmic Potential
Transmembrane520 – 54021Helical; Potential
Topological domain541 – 56525Extracellular Potential
Transmembrane566 – 58621Helical; Potential
Topological domain587 – 60620Cytoplasmic Potential
Transmembrane607 – 62721Helical; Potential
Topological domain628 – 731104Extracellular Potential
Transmembrane732 – 75221Helical; Potential
Topological domain753 – 79139Cytoplasmic Potential
Transmembrane792 – 81221Helical; Potential
Topological domain813 – 88270Extracellular Potential
Transmembrane883 – 90321Helical; Potential
Topological domain904 – 98683Cytoplasmic Potential

Amino acid modifications

Glycosylation8321N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 116116Missing in isoform 2.
VSP_025665
Alternative sequence1 – 2828Missing in isoform 3.
VSP_025666
Alternative sequence29 – 368GYLPSEGT → MLTRPSQV in isoform 3.
VSP_025667
Alternative sequence448 – 4514Missing in isoform 2 and isoform 3.
VSP_025668
Alternative sequence476 – 50126Missing in isoform 2 and isoform 3.
VSP_025669
Alternative sequence651 – 70050CAPGG…KQQSP → VTEILFISGSPFCLAYDLST PCTWEKQLQHICSAKSSRFL SFLLETFLFP in isoform 3.
VSP_025670
Alternative sequence701 – 986286Missing in isoform 3.
VSP_025671
Natural variant6081F → S.
Corresponds to variant rs2186797 [ dbSNP | Ensembl ].
VAR_032417
Natural variant9831G → R.
Corresponds to variant rs3740722 [ dbSNP | Ensembl ].
VAR_032418

Experimental info

Sequence conflict2021T → A in BAF85777. Ref.2
Sequence conflict8011N → D in AAH33036. Ref.3
Sequence conflict9481W → C in AAH33036. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 23, 2004. Version 1.
Checksum: E30A02F91EF36FC2

FASTA986114,078
        10         20         30         40         50         60 
MRVNEKYSTL PAEDRSVHII NICAIEDIGY LPSEGTLLNS LSVDPDAECK YGLYFRDGRR 

        70         80         90        100        110        120 
KVDYILVYHH KRPSGNRTLV RRVQHSDTPS GARSVKQDHP LPGKGASLDA GSGEPPMDYH 

       130        140        150        160        170        180 
EDDKRFRREE YEGNLLEAGL ELERDEDTKI HGVGFVKIHA PWNVLCREAE FLKLKMPTKK 

       190        200        210        220        230        240 
MYHINETRGL LKKINSVLQK ITDPIQPKVA EHRPQTMKRL SYPFSREKQH LFDLSDKDSF 

       250        260        270        280        290        300 
FDSKTRSTIV YEILKRTTCT KAKYSMGITS LLANGVYAAA YPLHDGDYNG ENVEFNDRKL 

       310        320        330        340        350        360 
LYEEWARYGV FYKYQPIDLV RKYFGEKIGL YFAWLGVYTQ MLIPASIVGI IVFLYGCATM 

       370        380        390        400        410        420 
DENIPSMEMC DQRHNITMCP LCDKTCSYWK MSSACATARA SHLFDNPATV FFSVFMALWA 

       430        440        450        460        470        480 
ATFMEHWKRK QMRLNYRWDL TGFEEEEEAV KDHPRAEYEA RVLEKSLKKE SRNKEKRRHI 

       490        500        510        520        530        540 
PEESTNKWKQ RVKTAMAGVK LTDKVKLTWR DRFPAYLTNL VSIIFMIAVT FAIVLGVIIY 

       550        560        570        580        590        600 
RISMAAALAM NSSPSVRSNI RVTVTATAVI INLVVIILLD EVYGCIARWL TKIEVPKTEK 

       610        620        630        640        650        660 
SFEERLIFKA FLLKFVNSYT PIFYVAFFKG RFVGRPGDYV YIFRSFRMEE CAPGGCLMEL 

       670        680        690        700        710        720 
CIQLSIIMLG KQLIQNNLFE IGIPKMKKLI RYLKLKQQSP PDHEECVKRK QRYEVDYNLE 

       730        740        750        760        770        780 
PFAGLTPEYM EMIIQFGFVT LFVASFPLAP LFALLNNIIE IRLDAKKFVT ELRRPVAVRA 

       790        800        810        820        830        840 
KDIGIWYNIL RGIGKLAVII NAFVISFTSD FIPRLVYLYM YSKNGTMHGF VNHTLSSFNV 

       850        860        870        880        890        900 
SDFQNGTAPN DPLDLGYEVQ ICRYKDYREP PWSENKYDIS KDFWAVLAAR LAFVIVFQNL 

       910        920        930        940        950        960 
VMFMSDFVDW VIPDIPKDIS QQIHKEKVLM VELFMREEQD KQQLLETWME KERQKDEPPC 

       970        980 
NHHNTKACPD SLGSPAPSHA YHGGVL 

« Hide

Isoform 2 [UniParc].

Checksum: 43B0D18B6FD82C3A
Show »

FASTA84097,736
Isoform 3 [UniParc].

Checksum: 6F7B524B54FD032B
Show »

FASTA64274,369

References

« Hide 'large scale' references
[1]"Comprehensive genome and transcriptome analysis of the 11q13 amplicon in human oral cancer and synteny to the 7F5 amplicon in murine oral carcinoma."
Huang X., Godfrey T.E., Gooding W.E., McCarty K.S. Jr., Gollin S.M.
Genes Chromosomes Cancer 45:1058-1069(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Testis and Uterus.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[4]"FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products."
Katoh M., Katoh M.
Int. J. Oncol. 22:1375-1381(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION, TOPOLOGY.
[5]"The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status."
West R.B., Corless C.L., Chen X., Rubin B.P., Subramanian S., Montgomery K., Zhu S., Ball C.A., Nielsen T.O., Patel R., Goldblum J.R., Brown P.O., Heinrich M.C., van de Rijn M.
Am. J. Pathol. 165:107-113(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display."
Carles A., Millon R., Cromer A., Ganguli G., Lemaire F., Young J., Wasylyk C., Muller D., Schultz I., Rabouel Y., Dembele D., Zhao C., Marchal P., Ducray C., Bracco L., Abecassis J., Poch O., Wasylyk B.
Oncogene 25:1821-1831(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Expression and function of epithelial anoctamins."
Schreiber R., Uliyakina I., Kongsuphol P., Warth R., Mirza M., Martins J.R., Kunzelmann K.
J. Biol. Chem. 285:7838-7845(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]"TMEM16A protein: a new identity for Ca(2+)-dependent Cl? channels."
Ferrera L., Caputo A., Galietta L.J.
Physiology (Bethesda) 25:357-363(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels?"
Duran C., Hartzell H.C.
Acta Pharmacol. Sin. 32:685-692(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"CFTR and TMEM16A are separate but functionally related Cl-channels."
Ousingsawat J., Kongsuphol P., Schreiber R., Kunzelmann K.
Cell. Physiol. Biochem. 28:715-724(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CFTR, ENZYME REGULATION.
[12]"Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A."
Sheridan J.T., Worthington E.N., Yu K., Gabriel S.E., Hartzell H.C., Tarran R.
J. Biol. Chem. 286:1381-1388(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[13]"Anoctamins."
Kunzelmann K., Tian Y., Martins J.R., Faria D., Kongsuphol P., Ousingsawat J., Thevenod F., Roussa E., Rock J., Schreiber R.
Pflugers Arch. 462:195-208(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"The anoctamin (TMEM16) gene family: calcium-activated chloride channels come of age."
Winpenny J.P., Gray M.A.
Exp. Physiol. 97:175-176(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"The anoctamin family: TMEM16A and TMEM16B as calcium-activated chloride channels."
Scudieri P., Sondo E., Ferrera L., Galietta L.J.
Exp. Physiol. 97:177-183(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW, FUNCTION, SUBCELLULAR LOCATION.
[16]"Expression and function of epithelial anoctamins."
Kunzelmann K., Schreiber R., Kmit A., Jantarajit W., Martins J.R., Faria D., Kongsuphol P., Ousingsawat J., Tian Y.
Exp. Physiol. 97:184-192(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[17]"Anoctamins are a family of Ca2+ activated Cl- channels."
Tian Y., Schreiber R., Kunzelmann K.
J. Cell Sci. 125:4991-4998(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY728143 mRNA. Translation: AAU82085.1.
AK097619 mRNA. Translation: BAC05123.1.
AK293088 mRNA. Translation: BAF85777.1.
BC033036 mRNA. Translation: AAH33036.2.
RefSeqNP_060513.5. NM_018043.5.
UniGeneHs.503074.

3D structure databases

ProteinModelPortalQ5XXA6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120417. 1 interaction.
IntActQ5XXA6. 1 interaction.
STRING9606.ENSP00000347454.

Chemistry

ChEMBLCHEMBL2046267.
GuidetoPHARMACOLOGY708.

Protein family/group databases

TCDB1.A.17.1.1. the calcium-dependent chloride channel (ca-clc) family.

PTM databases

PhosphoSiteQ5XXA6.

Polymorphism databases

DMDM74708278.

Proteomic databases

PaxDbQ5XXA6.
PRIDEQ5XXA6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316296; ENSP00000319477; ENSG00000131620. [Q5XXA6-3]
ENST00000355303; ENSP00000347454; ENSG00000131620. [Q5XXA6-1]
ENST00000398543; ENSP00000381551; ENSG00000131620. [Q5XXA6-2]
ENST00000530676; ENSP00000435797; ENSG00000131620. [Q5XXA6-2]
GeneID55107.
KEGGhsa:55107.
UCSCuc001opj.3. human. [Q5XXA6-1]
uc001opk.1. human. [Q5XXA6-3]

Organism-specific databases

CTD55107.
GeneCardsGC11P069927.
HGNCHGNC:21625. ANO1.
HPAHPA032148.
MIM610108. gene.
neXtProtNX_Q5XXA6.
PharmGKBPA164715378.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320103.
HOGENOMHOG000006509.
HOVERGENHBG069519.
InParanoidQ5XXA6.
OMADPDAECK.
OrthoDBEOG7BS48W.
PhylomeDBQ5XXA6.
TreeFamTF314265.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ5XXA6.
BgeeQ5XXA6.
CleanExHS_ANO1.
GenevestigatorQ5XXA6.

Family and domain databases

InterProIPR007632. Anoctamin.
[Graphical view]
PANTHERPTHR12308. PTHR12308. 1 hit.
PfamPF04547. Anoctamin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiANO1.
GenomeRNAi55107.
NextBio58717.
PROQ5XXA6.
SOURCESearch...

Entry information

Entry nameANO1_HUMAN
AccessionPrimary (citable) accession number: Q5XXA6
Secondary accession number(s): A8KAM3, Q8IYY8, Q8N7V3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: November 23, 2004
Last modified: April 16, 2014
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM