Q5XXA6 (ANO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 74.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 986 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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 | |
| 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. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Ion transport Transport |
| Cellular component | Cell membrane Cytoplasm Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Transmembrane Transmembrane helix |
| Ligand | Calcium Chloride |
| Molecular function | Chloride channel Developmental protein Ion channel |
| PTM | Glycoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological_process | multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW |
| Cellular_component | chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmInferred from electronic annotation. Source: UniProtKB-SubCell plasma membraneInferred from direct assay Ref.15Ref.11. Source: UniProtKB |
| Molecular_function | intracellular calcium activated chloride channel activity Inferred from direct assay Ref.15. Source: UniProtKB |
| Complete GO annotation... | |
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 986 | 986 | Anoctamin-1 | PRO_0000288435 | |||||
Regions | |||||||||
| Topological domain | 1 – 333 | 333 | Cytoplasmic Potential | ||||||
| Transmembrane | 334 – 354 | 21 | Helical; Potential | ||||||
| Topological domain | 355 – 402 | 48 | Extracellular Potential | ||||||
| Transmembrane | 403 – 423 | 21 | Helical; Potential | ||||||
| Topological domain | 424 – 519 | 96 | Cytoplasmic Potential | ||||||
| Transmembrane | 520 – 540 | 21 | Helical; Potential | ||||||
| Topological domain | 541 – 565 | 25 | Extracellular Potential | ||||||
| Transmembrane | 566 – 586 | 21 | Helical; Potential | ||||||
| Topological domain | 587 – 606 | 20 | Cytoplasmic Potential | ||||||
| Transmembrane | 607 – 627 | 21 | Helical; Potential | ||||||
| Topological domain | 628 – 731 | 104 | Extracellular Potential | ||||||
| Transmembrane | 732 – 752 | 21 | Helical; Potential | ||||||
| Topological domain | 753 – 791 | 39 | Cytoplasmic Potential | ||||||
| Transmembrane | 792 – 812 | 21 | Helical; Potential | ||||||
| Topological domain | 813 – 882 | 70 | Extracellular Potential | ||||||
| Transmembrane | 883 – 903 | 21 | Helical; Potential | ||||||
| Topological domain | 904 – 986 | 83 | Cytoplasmic Potential | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 832 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 116 | 116 | Missing in isoform 2. | VSP_025665 | |||||
| Alternative sequence | 1 – 28 | 28 | Missing in isoform 3. | VSP_025666 | |||||
| Alternative sequence | 29 – 36 | 8 | GYLPSEGT → MLTRPSQV in isoform 3. | VSP_025667 | |||||
| Alternative sequence | 448 – 451 | 4 | Missing in isoform 2 and isoform 3. | VSP_025668 | |||||
| Alternative sequence | 476 – 501 | 26 | Missing in isoform 2 and isoform 3. | VSP_025669 | |||||
| Alternative sequence | 651 – 700 | 50 | CAPGG…KQQSP → VTEILFISGSPFCLAYDLST PCTWEKQLQHICSAKSSRFL SFLLETFLFP in isoform 3. | VSP_025670 | |||||
| Alternative sequence | 701 – 986 | 286 | Missing in isoform 3. | VSP_025671 | |||||
| Natural variant | 608 | 1 | F → S. Corresponds to variant rs2186797 [ dbSNP | Ensembl ]. | VAR_032417 | |||||
| Natural variant | 983 | 1 | G → R. Corresponds to variant rs3740722 [ dbSNP | Ensembl ]. | VAR_032418 | |||||
Experimental info | |||||||||
| Sequence conflict | 202 | 1 | T → A in BAF85777. Ref.2 | ||||||
| Sequence conflict | 801 | 1 | N → D in AAH33036. Ref.3 | ||||||
| Sequence conflict | 948 | 1 | W → C in AAH33036. Ref.3 | ||||||
Sequences
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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. 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. |
| IPI | IPI00384668. IPI00395839. IPI00873502. |
| RefSeq | NP_060513.5. NM_018043.5. |
| UniGene | Hs.503074. |
3D structure databases | |
| ProteinModelPortal | Q5XXA6. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | 9606.ENSP00000347454. |
Protein family/group databases | |
| TCDB | 1.A.17.1.1. calcium-dependent chloride channel (Ca-ClC) family. |
PTM databases | |
| PhosphoSite | Q5XXA6. |
Polymorphism databases | |
| DMDM | 74708278. |
Proteomic databases | |
| PaxDb | Q5XXA6. |
| PRIDE | Q5XXA6. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000316296; ENSP00000319477; ENSG00000131620. ENST00000355303; ENSP00000347454; ENSG00000131620. ENST00000398543; ENSP00000381551; ENSG00000131620. ENST00000530676; ENSP00000435797; ENSG00000131620. |
| GeneID | 55107. |
| KEGG | hsa:55107. |
| UCSC | uc001opj.3. human. uc001opk.1. human. |
Organism-specific databases | |
| CTD | 55107. |
| GeneCards | GC11P069925. |
| HGNC | HGNC:21625. ANO1. |
| HPA | HPA032148. |
| MIM | 610108. gene. |
| neXtProt | NX_Q5XXA6. |
| PharmGKB | PA164715378. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG320103. |
| HOGENOM | HOG000006509. |
| HOVERGEN | HBG069519. |
| InParanoid | Q5XXA6. |
| OMA | DPDAECK. |
| OrthoDB | EOG47SSD0. |
Gene expression databases | |
| ArrayExpress | Q5XXA6. |
| Bgee | Q5XXA6. |
| CleanEx | HS_ANO1. |
| Genevestigator | Q5XXA6. |
Family and domain databases | |
| InterPro | IPR007632. Anoctamin. [Graphical view] |
| PANTHER | PTHR12308. PTHR12308. 1 hit. |
| Pfam | PF04547. Anoctamin. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 55107. |
| NextBio | 58717. |
| SOURCE | Search... |
Entry information
| Entry name | ANO1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q5XXA6 Secondary accession number(s): A8KAM3, Q8IYY8, Q8N7V3 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
