Q4KMQ2 (ANO6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Anoctamin-6

Alternative name(s):
Small-conductance calcium-activated nonselective cation channel
Short name=SCAN channel
Transmembrane protein 16F

Gene names

Name:	ANO6
Synonyms:	TMEM16F

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	910 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets and osteoblasts. Phospholipid scrambling results in surface exposure of phosphatidylserine which in platelets is essential to trigger the clotting system whereas in osteoblasts is essential for the deposition of hydroxyapatite during bone mineralization. Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes. Ref.6 Ref.7 Ref.10 Ref.14 Ref.15
Enzyme regulation	Exhibits synergistic gating by Ca2+ and voltage. Inhibited by some non-specific cation channel blockers such as: ruthenium red, 2-aminoethyl diphenylborinate (2APB), gadolinium and cadmium ions By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Shows an intracellular localization according to Ref.11. Ref.6 Ref.7 Ref.11 Ref.15
Tissue specificity	Expressed in embryonic stem cell, fetal liver, retina, chronic myologenous leukemia and intestinal cancer. Ref.4
Involvement in disease	Scott syndrome (SCTS) [MIM:262890]: A mild bleeding disorder due to impaired surface exposure of procoagulant phosphatidylserine (PS) on platelets and other blood cells, following activation with Ca(2+)-elevating agents. Note: The disease is caused by mutations affecting the gene represented in this entry.
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 Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of blood coagulation via clotting cascade Inferred from mutant phenotype Ref.7. Source: UniProtKB blood coagulation Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylserine exposure on blood platelet Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from direct assay Ref.11. Source: UniProtKB plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	calcium activated cation channel activity Inferred from sequence or structural similarity. Source: UniProtKB chloride channel activity Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated ion channel activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q4KMQ2-1)

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: Q4KMQ2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     23-23: I → IGDVPASRRPFLTPHTHLPSSL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 910	910	Anoctamin-6		PRO_0000191757
Regions
	Topological domain	1 – 294	294	Cytoplasmic Potential
	Transmembrane	295 – 315	21	Helical; Potential
	Topological domain	316 – 375	60	Extracellular Potential
	Transmembrane	376 – 396	21	Helical; Potential
	Topological domain	397 – 454	58	Cytoplasmic Potential
	Transmembrane	455 – 475	21	Helical; Potential
	Topological domain	476 – 513	38	Extracellular Potential
	Transmembrane	514 – 534	21	Helical; Potential
	Topological domain	535 – 551	17	Cytoplasmic Potential
	Transmembrane	552 – 572	21	Helical; Potential
	Topological domain	573 – 669	97	Extracellular Potential
	Transmembrane	670 – 690	21	Helical; Potential
	Topological domain	691 – 725	35	Cytoplasmic Potential
	Transmembrane	726 – 746	21	Helical; Potential
	Topological domain	747 – 824	78	Extracellular Potential
	Transmembrane	825 – 845	21	Helical; Potential
	Topological domain	846 – 910	65	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	329	1	N-linked (GlcNAc...) Potential
	Glycosylation	361	1	N-linked (GlcNAc...) Potential
	Glycosylation	493	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	777	1	N-linked (GlcNAc...) Potential
	Glycosylation	790	1	N-linked (GlcNAc...) Potential
	Glycosylation	802	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	23	1	I → IGDVPASRRPFLTPHTHLPS SL in isoform 2.		VSP_042893
	Natural variant	128	1	A → T. Corresponds to variant rs2162321 [ dbSNP | Ensembl ].		VAR_028109
Experimental info
	Sequence conflict	837	1	F → L in AAH98410. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 8F7F1CB78FAAEB78	FASTA	910	106,165
	10 20 30 40 50 60 MKKMSRNVLL QMEEEEDDDD GDIVLENLGQ TIVPDLGSLE SQHDFRTPEF EEFNGKPDSL 70 80 90 100 110 120 FFNDGQRRID FVLVYEDESR KETNKKGTNE KQRRKRQAYE SNLICHGLQL EATRSVLDDK 130 140 150 160 170 180 LVFVKVHAPW EVLCTYAEIM HIKLPLKPND LKNRSSAFGT LNWFTKVLSV DESIIKPEQE 190 200 210 220 230 240 FFTAPFEKNR MNDFYIVDRD AFFNPATRSR IVYFILSRVK YQVINNVSKF GINRLVNSGI 250 260 270 280 290 300 YKAAFPLHDC KFRRQSEDPS CPNERYLLYR EWAHPRSIYK KQPLDLIRKY YGEKIGIYFA 310 320 330 340 350 360 WLGYYTQMLL LAAVVGVACF LYGYLNQDNC TWSKEVCHPD IGGKIIMCPQ CDRLCPFWKL 370 380 390 400 410 420 NITCESSKKL CIFDSFGTLV FAVFMGVWVT LFLEFWKRRQ AELEYEWDTV ELQQEEQARP 430 440 450 460 470 480 EYEARCTHVV INEITQEEER IPFTAWGKCI RITLCASAVF FWILLIIASV IGIIVYRLSV 490 500 510 520 530 540 FIVFSAKLPK NINGTDPIQK YLTPQTATSI TASIISFIII MILNTIYEKV AIMITNFELP 550 560 570 580 590 600 RTQTDYENSL TMKMFLFQFV NYYSSCFYIA FFKGKFVGYP GDPVYWLGKY RNEECDPGGC 610 620 630 640 650 660 LLELTTQLTI IMGGKAIWNN IQEVLLPWIM NLIGRFHRVS GSEKITPRWE QDYHLQPMGK 670 680 690 700 710 720 LGLFYEYLEM IIQFGFVTLF VASFPLAPLL ALVNNILEIR VDAWKLTTQF RRLVPEKAQD 730 740 750 760 770 780 IGAWQPIMQG IAILAVVTNA MIIAFTSDMI PRLVYYWSFS VPPYGDHTSY TMEGYINNTL 790 800 810 820 830 840 SIFKVADFKN KSKGNPYSDL GNHTTCRYRD FRYPPGHPQE YKHNIYYWHV IAAKLAFIIV 850 860 870 880 890 900 MEHVIYSVKF FISYAIPDVS KRTKSKIQRE KYLTQKLLHE NHLKDMTKNM GVIAERMIEA 910 VDNNLRPKSE
	Isoform 2 [UniParc]. Checksum: 6F0149C7FB67A371	FASTA	931	108,433
	10 20 30 40 50 60 MKKMSRNVLL QMEEEEDDDD GDIGDVPASR RPFLTPHTHL PSSLVLENLG QTIVPDLGSL 70 80 90 100 110 120 ESQHDFRTPE FEEFNGKPDS LFFNDGQRRI DFVLVYEDES RKETNKKGTN EKQRRKRQAY 130 140 150 160 170 180 ESNLICHGLQ LEATRSVLDD KLVFVKVHAP WEVLCTYAEI MHIKLPLKPN DLKNRSSAFG 190 200 210 220 230 240 TLNWFTKVLS VDESIIKPEQ EFFTAPFEKN RMNDFYIVDR DAFFNPATRS RIVYFILSRV 250 260 270 280 290 300 KYQVINNVSK FGINRLVNSG IYKAAFPLHD CKFRRQSEDP SCPNERYLLY REWAHPRSIY 310 320 330 340 350 360 KKQPLDLIRK YYGEKIGIYF AWLGYYTQML LLAAVVGVAC FLYGYLNQDN CTWSKEVCHP 370 380 390 400 410 420 DIGGKIIMCP QCDRLCPFWK LNITCESSKK LCIFDSFGTL VFAVFMGVWV TLFLEFWKRR 430 440 450 460 470 480 QAELEYEWDT VELQQEEQAR PEYEARCTHV VINEITQEEE RIPFTAWGKC IRITLCASAV 490 500 510 520 530 540 FFWILLIIAS VIGIIVYRLS VFIVFSAKLP KNINGTDPIQ KYLTPQTATS ITASIISFII 550 560 570 580 590 600 IMILNTIYEK VAIMITNFEL PRTQTDYENS LTMKMFLFQF VNYYSSCFYI AFFKGKFVGY 610 620 630 640 650 660 PGDPVYWLGK YRNEECDPGG CLLELTTQLT IIMGGKAIWN NIQEVLLPWI MNLIGRFHRV 670 680 690 700 710 720 SGSEKITPRW EQDYHLQPMG KLGLFYEYLE MIIQFGFVTL FVASFPLAPL LALVNNILEI 730 740 750 760 770 780 RVDAWKLTTQ FRRLVPEKAQ DIGAWQPIMQ GIAILAVVTN AMIIAFTSDM IPRLVYYWSF 790 800 810 820 830 840 SVPPYGDHTS YTMEGYINNT LSIFKVADFK NKSKGNPYSD LGNHTTCRYR DFRYPPGHPQ 850 860 870 880 890 900 EYKHNIYYWH VIAAKLAFII VMEHVIYSVK FFISYAIPDV SKRTKSKIQR EKYLTQKLLH 910 920 930 ENHLKDMTKN MGVIAERMIE AVDNNLRPKS E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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] (ISOFORMS 1 AND 2). Tissue: Placenta and Testis.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 772-910 (ISOFORM 1/2). Tissue: Adipose tissue.
[4]	"Identification and characterization of TMEM16E and TMEM16F genes in silico." Katoh M., Katoh M. Int. J. Oncol. 24:1345-1349(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-493, MASS SPECTROMETRY. Tissue: Liver.
[6]	"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.
[7]	"Calcium-dependent phospholipid scrambling by TMEM16F." Suzuki J., Umeda M., Sims P.J., Nagata S. Nature 468:834-838(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN SCOTT SYNDROME.
[8]	"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.
[9]	"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.
[10]	"Anoctamin 6 is an essential component of the outwardly rectifying chloride channel." Martins J.R., Faria D., Kongsuphol P., Reisch B., Schreiber R., Kunzelmann K. Proc. Natl. Acad. Sci. U.S.A. 108:18168-18172(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins." Duran C., Qu Z., Osunkoya A.O., Cui Y., Hartzell H.C. Am. J. Physiol. 302:C482-C493(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"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.
[13]	"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, ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY.
[14]	"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, FUNCTION.
[15]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC009248 Genomic DNA. No translation available. AC009778 Genomic DNA. No translation available. AC063924 Genomic DNA. No translation available. BC098410 mRNA. Translation: AAH98410.1. BC136445 mRNA. Translation: AAI36446.1. AL833405 mRNA. Translation: CAD38638.1.
IPI	IPI00151710. IPI00790445.
RefSeq	NP_001020527.2. NM_001025356.2. NP_001136150.1. NM_001142678.1. NP_001136151.1. NM_001142679.1. NP_001191732.1. NM_001204803.1.
UniGene	Hs.505339.
3D structure databases
ProteinModelPortal	Q4KMQ2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q4KMQ2. 1 interaction.
STRING	9606.ENSP00000391417.
PTM databases
PhosphoSite	Q4KMQ2.
Polymorphism databases
DMDM	116242820.
Proteomic databases
PaxDb	Q4KMQ2.
PRIDE	Q4KMQ2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320560; ENSP00000320087; ENSG00000177119. ENST00000423947; ENSP00000409126; ENSG00000177119.
GeneID	196527.
KEGG	hsa:196527.
UCSC	uc001roo.3. human.
Organism-specific databases
CTD	196527.
GeneCards	GC12P045609.
H-InvDB	HIX0010565.
HGNC	HGNC:25240. ANO6.
HPA	HPA038958.
MIM	262890. phenotype. 608663. gene.
neXtProt	NX_Q4KMQ2.
Orphanet	806. Scott syndrome.
PharmGKB	PA164715690.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320103.
HOGENOM	HOG000006509.
HOVERGEN	HBG069519.
InParanoid	Q4KMQ2.
OMA	GVWVTLF.
Gene expression databases
ArrayExpress	Q4KMQ2.
Bgee	Q4KMQ2.
CleanEx	HS_ANO6.
Genevestigator	Q4KMQ2.
Family and domain databases
InterPro	IPR007632. Anoctamin. [Graphical view]
PANTHER	PTHR12308. PTHR12308. 1 hit.
Pfam	PF04547. Anoctamin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ANO6. human.
GenomeRNAi	196527.
NextBio	89521.
SOURCE	Search...

Entry information

Entry name

ANO6_HUMAN

Accession

Primary (citable) accession number: Q4KMQ2
Secondary accession number(s): A6NNM6 , B9EGG0, E7ENK4, Q8N3Q2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 76 of the entry and version 2 of the sequence. [Complete history]

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.