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Protein

Anoctamin-6

Gene

Ano6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets, osteoblasts and fetal thymocytes. 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. Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide. Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes.5 Publications

Enzyme regulationi

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.1 Publication

GO - Molecular functioni

  • calcium activated cation channel activity Source: UniProtKB
  • intracellular calcium activated chloride channel activity Source: MGI
  • phospholipid scramblase activity Source: MGI
  • protein homodimerization activity Source: MGI
  • voltage-gated chloride channel activity Source: MGI
  • voltage-gated ion channel activity Source: UniProtKB

GO - Biological processi

  • activation of blood coagulation via clotting cascade Source: MGI
  • bleb assembly Source: UniProtKB
  • blood coagulation Source: UniProtKB
  • bone mineralization involved in bone maturation Source: MGI
  • calcium activated galactosylceramide scrambling Source: MGI
  • calcium activated phosphatidylcholine scrambling Source: MGI
  • calcium activated phosphatidylserine scrambling Source: MGI
  • calcium activated phospholipid scrambling Source: MGI
  • calcium ion transmembrane transport Source: UniProtKB
  • cation transport Source: MGI
  • chloride transmembrane transport Source: UniProtKB
  • chloride transport Source: MGI
  • dendritic cell chemotaxis Source: MGI
  • negative regulation of cell volume Source: UniProtKB
  • phosphatidylserine exposure on blood platelet Source: MGI
  • phospholipid scrambling Source: UniProtKB
  • pore complex assembly Source: MGI
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of bone mineralization Source: UniProtKB
  • positive regulation of endothelial cell apoptotic process Source: MGI
  • positive regulation of ion transmembrane transport Source: UniProtKB
  • positive regulation of monocyte chemotaxis Source: UniProtKB
  • positive regulation of phagocytosis, engulfment Source: UniProtKB
  • positive regulation of potassium ion export Source: BHF-UCL
  • purinergic nucleotide receptor signaling pathway Source: UniProtKB
  • sodium ion transmembrane transport Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Lipid transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.
R-MMU-6798695. Neutrophil degranulation.

Chemistry databases

SwissLipidsiSLP:000000373.

Names & Taxonomyi

Protein namesi
Recommended name:
Anoctamin-6
Alternative name(s):
Small-conductance calcium-activated nonselective cation channel
Short name:
SCAN channel
Transmembrane protein 16F
Gene namesi
Name:Ano6
Synonyms:Tmem16f
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2145890. Ano6.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity

  • Note: Shows an intracellular localization.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 295CytoplasmicSequence analysisAdd BLAST295
Transmembranei296 – 316HelicalSequence analysisAdd BLAST21
Topological domaini317 – 376ExtracellularSequence analysisAdd BLAST60
Transmembranei377 – 397HelicalSequence analysisAdd BLAST21
Topological domaini398 – 455CytoplasmicSequence analysisAdd BLAST58
Transmembranei456 – 476HelicalSequence analysisAdd BLAST21
Topological domaini477 – 514ExtracellularSequence analysisAdd BLAST38
Transmembranei515 – 535HelicalSequence analysisAdd BLAST21
Topological domaini536 – 552CytoplasmicSequence analysisAdd BLAST17
Transmembranei553 – 573HelicalSequence analysisAdd BLAST21
Topological domaini574 – 670ExtracellularSequence analysisAdd BLAST97
Transmembranei671 – 691HelicalSequence analysisAdd BLAST21
Topological domaini692 – 726CytoplasmicSequence analysisAdd BLAST35
Transmembranei727 – 747HelicalSequence analysisAdd BLAST21
Topological domaini748 – 825ExtracellularSequence analysisAdd BLAST78
Transmembranei826 – 846HelicalSequence analysisAdd BLAST21
Topological domaini847 – 911CytoplasmicSequence analysisAdd BLAST65

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice exhibit deficiencies in Ca2+-dependent phospholipid scramblase activity in platelets and defects in blood coagulation. They also show reduced skeleton size and skeletal deformities.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi409D → G: Reduced activity and sensitivity to Ca(2+). 1 Publication1
Mutagenesisi559Q → K: Increased permeability to chloride ions. 1 Publication1
Mutagenesisi667E → Q: Significant reduction in sensitivity to Ca(2+). 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001917581 – 911Anoctamin-6Add BLAST911

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi330N-linked (GlcNAc...)Sequence analysis1
Glycosylationi362N-linked (GlcNAc...)Sequence analysis1
Glycosylationi492N-linked (GlcNAc...); atypical1 Publication1
Glycosylationi494N-linked (GlcNAc...)1 Publication1
Glycosylationi778N-linked (GlcNAc...)Sequence analysis1
Glycosylationi785N-linked (GlcNAc...)1 Publication1
Glycosylationi803N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ6P9J9.
PaxDbiQ6P9J9.
PeptideAtlasiQ6P9J9.
PRIDEiQ6P9J9.

PTM databases

iPTMnetiQ6P9J9.
PhosphoSitePlusiQ6P9J9.
SwissPalmiQ6P9J9.

Expressioni

Tissue specificityi

Predominant expression seen in epithelial tissues. Also found in skeletal system where it is primarily expressed in osteoblasts.2 Publications

Developmental stagei

At E14.5, expressed in lung epithelium and mesenchyme. At E16.5, expressed in esophageal epithelium and mesenchyme. In the caudal digestive tract, detected in small intestine epithelium at E14.5. Also detected at E14.5 in epithelium and mesenchyme of trachea, ovary, kidney and stomach. In the developing skeleton, expressed in developing rib perichondria at E14.5. Also expressed in the neural tube and dorsal root ganglia at E14.5. In developing skin, expression is restricted to basal layers of the epidermis at E16.5.1 Publication

Gene expression databases

BgeeiENSMUSG00000064210.
GenevisibleiQ6P9J9. MM.

Interactioni

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

IntActiQ6P9J9. 2 interactors.
MINTiMINT-4114114.
STRINGi10090.ENSMUSP00000071770.

Structurei

3D structure databases

ProteinModelPortaliQ6P9J9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the anoctamin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2514. Eukaryota.
ENOG410XS4S. LUCA.
GeneTreeiENSGT00760000119015.
HOGENOMiHOG000006509.
HOVERGENiHBG069519.
InParanoidiQ6P9J9.
KOiK19500.
OMAiKHNIYYW.
OrthoDBiEOG091G01JF.
PhylomeDBiQ6P9J9.
TreeFamiTF314265.

Family and domain databases

InterProiIPR032394. Anoct_dimer.
IPR007632. Anoctamin.
IPR031295. Anoctamin-6.
[Graphical view]
PANTHERiPTHR12308. PTHR12308. 1 hit.
PTHR12308:SF21. PTHR12308:SF21. 1 hit.
PfamiPF16178. Anoct_dimer. 1 hit.
PF04547. Anoctamin. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6P9J9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQMMTRKVLL NMELEEDDDE DGDIVLENFD QTIVCPTFGS LENQQDFRTP
60 70 80 90 100
EFEEFNGKPD SLFFTDGQRR IDFILVYEDE SKKENNKKGT NEKQKRKRQA
110 120 130 140 150
YESNLICHGL QLEATRSVSD DKLVFVKVHA PWEVLCTYAE IMHIKLPLKP
160 170 180 190 200
NDLKTRSPFG NLNWFTKVLR VNESVIKPEQ EFFTAPFEKS RMNDFYILDR
210 220 230 240 250
DSFFNPATRS RIVYFILSRV KYQVMNNVNK FGINRLVSSG IYKAAFPLHD
260 270 280 290 300
CRFNYESEDI SCPSERYLLY REWAHPRSIY KKQPLDLIRK YYGEKIGIYF
310 320 330 340 350
AWLGYYTQML LLAAVVGVAC FLYGYLDQDN CTWSKEVCDP DIGGQILMCP
360 370 380 390 400
QCDRLCPFWR LNITCESSKK LCIFDSFGTL IFAVFMGVWV TLFLEFWKRR
410 420 430 440 450
QAELEYEWDT VELQQEEQAR PEYEAQCNHV VINEITQEEE RIPFTTCGKC
460 470 480 490 500
IRVTLCASAV FFWILLIIAS VIGIIVYRLS VFIVFSTTLP KNPNGTDPIQ
510 520 530 540 550
KYLTPQMATS ITASIISFII IMILNTIYEK VAIMITNFEL PRTQTDYENS
560 570 580 590 600
LTMKMFLFQF VNYYSSCFYI AFFKGKFVGY PGDPVYLLGK YRSEECDPGG
610 620 630 640 650
CLLELTTQLT IIMGGKAIWN NIQEVLLPWV MNLIGRYKRV SGSEKITPRW
660 670 680 690 700
EQDYHLQPMG KLGLFYEYLE MIIQFGFVTL FVASFPLAPL LALVNNILEI
710 720 730 740 750
RVDAWKLTTQ FRRMVPEKAQ DIGAWQPIMQ GIAILAVVTN AMIIAFTSDM
760 770 780 790 800
IPRLVYYWSF SIPPYGDHTY YTMDGYINNT LSVFNITDFK NTDKENPYIG
810 820 830 840 850
LGNYTLCRYR DFRNPPGHPQ EYKHNIYYWH VIAAKLAFII VMEHIIYSVK
860 870 880 890 900
FFISYAIPDV SKITKSKIKR EKYLTQKLLH ESHLKDLTKN MGIIAERIGG
910
TVDNSVRPKL E
Length:911
Mass (Da):106,255
Last modified:July 5, 2004 - v1
Checksum:i33D7A6EF02635B39
GO
Isoform 2 (identifier: Q6P9J9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-427: Missing.
     428-436: NHVVINEIT → MALMAESLC

Note: No experimental confirmation available.
Show »
Length:484
Mass (Da):55,725
Checksum:iC3DCED460A9892A7
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0156541 – 427Missing in isoform 2. 1 PublicationAdd BLAST427
Alternative sequenceiVSP_015655428 – 436NHVVINEIT → MALMAESLC in isoform 2. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK089300 mRNA. Translation: BAC40833.1.
BC060732 mRNA. Translation: AAH60732.1.
CCDSiCCDS37184.1. [Q6P9J9-1]
RefSeqiNP_001240742.1. NM_001253813.1.
NP_780553.2. NM_175344.4. [Q6P9J9-1]
UniGeneiMm.38087.

Genome annotation databases

EnsembliENSMUST00000071874; ENSMUSP00000071770; ENSMUSG00000064210. [Q6P9J9-1]
GeneIDi105722.
KEGGimmu:105722.
UCSCiuc007xju.2. mouse. [Q6P9J9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK089300 mRNA. Translation: BAC40833.1.
BC060732 mRNA. Translation: AAH60732.1.
CCDSiCCDS37184.1. [Q6P9J9-1]
RefSeqiNP_001240742.1. NM_001253813.1.
NP_780553.2. NM_175344.4. [Q6P9J9-1]
UniGeneiMm.38087.

3D structure databases

ProteinModelPortaliQ6P9J9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ6P9J9. 2 interactors.
MINTiMINT-4114114.
STRINGi10090.ENSMUSP00000071770.

Chemistry databases

SwissLipidsiSLP:000000373.

PTM databases

iPTMnetiQ6P9J9.
PhosphoSitePlusiQ6P9J9.
SwissPalmiQ6P9J9.

Proteomic databases

EPDiQ6P9J9.
PaxDbiQ6P9J9.
PeptideAtlasiQ6P9J9.
PRIDEiQ6P9J9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000071874; ENSMUSP00000071770; ENSMUSG00000064210. [Q6P9J9-1]
GeneIDi105722.
KEGGimmu:105722.
UCSCiuc007xju.2. mouse. [Q6P9J9-1]

Organism-specific databases

CTDi196527.
MGIiMGI:2145890. Ano6.

Phylogenomic databases

eggNOGiKOG2514. Eukaryota.
ENOG410XS4S. LUCA.
GeneTreeiENSGT00760000119015.
HOGENOMiHOG000006509.
HOVERGENiHBG069519.
InParanoidiQ6P9J9.
KOiK19500.
OMAiKHNIYYW.
OrthoDBiEOG091G01JF.
PhylomeDBiQ6P9J9.
TreeFamiTF314265.

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiAno6. mouse.
PROiQ6P9J9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000064210.
GenevisibleiQ6P9J9. MM.

Family and domain databases

InterProiIPR032394. Anoct_dimer.
IPR007632. Anoctamin.
IPR031295. Anoctamin-6.
[Graphical view]
PANTHERiPTHR12308. PTHR12308. 1 hit.
PTHR12308:SF21. PTHR12308:SF21. 1 hit.
PfamiPF16178. Anoct_dimer. 1 hit.
PF04547. Anoctamin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiANO6_MOUSE
AccessioniPrimary (citable) accession number: Q6P9J9
Secondary accession number(s): Q8C242
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.