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1.A.17.1.4
Anoctamin-6 (ANO6: TMEM16F) Ca2+-dependent phospholipid scramblase (flippase) (Suzuki et al., 2010; Chauhan et al. 2016). Defects cause Scott syndrome. It is an essential component of the outwardly rectifying chloride channel (Martins et al., 2011; Keramidas and Lynch 2012).  It has also been reported to be an anion channel with delayed Ca2+ activation (Adomaviciene et al. 2013) as well as a Ca2+-activated cation channel with activity that is required for lipid scrambing (Yang et al. 2012).  However, Suzuki et al. (2013) showed that TMEM16F is a Ca2+-dependent phospholipid scramblase that exposes phosphatidylserine (PS) to the cell surface but lacks calcium-dependent chloride channel activity.  TMEM16C, 16D, 16G and 16J also had Ca2+-dependent scramblase but not channel activity (Suzuki et al. 2013).  The pore region resonsible for Cl- transport in TMEM16A is also responsible for phospholipid scramblase activity (Suzuki et al. 2014).  Anoctamin-6 (Ano6) plays an essential role in C2C12 myoblast proliferation, probably by regulating the ERK/AKT signaling pathway (Zhao et al. 2014).  It regulates baeline phosphatidyl serine exposure and cell viability in human embryonic kidney cells (<Chauhan et al. 2016). Defects cause Scott syndrome. It is an essential component of the outwardly rectifying chloride channel (Martins et al., 2011; Keramidas and Lynch 2012).  It has also been reported to be an anion channel with delayed Ca2+ activation (Adomaviciene et al. 2013) as well as a Ca2+-activated cation channel with activity that is required for lipid scrambing (Yang et al. 2012).  However, Suzuki et al. (2013) showed that TMEM16F is a Ca2+-dependent phospholipid scramblase that exposes phosphatidylserine (PS) to the cell surface but lacks calcium-dependent chloride channel activity.  TMEM16C, 16D, 16G and 16J also had Ca2+-dependent scramblase but not channel activity (Suzuki et al. 2013).  The pore region resonsible for Cl- transport in TMEM16A is also responsible for phospholipid scramblase activity (Suzuki et al. 2014).  Anoctamin-6 (Ano6) plays an essential role in C2C12 myoblast proliferation, probably by regulating the ERK/AKT signaling pathway (Zhao et al. 2014).  It regulates baeline phosphatidyl serine exposure and cell viability in human embryonic kidney cells (Schenk et al. 2016).

Accession Number:Q4KMQ2
Protein Name:Anoctamin-6
Length:910
Molecular Weight:106165.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:9
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate phospholipids

Cross database links:

Genevestigator: Q4KMQ2
eggNOG: prNOG09936
Entrez Gene ID: 196527   
Pfam: PF04547   
KEGG: hsa:196527   

Gene Ontology

GO:0034707 C:chloride channel complex
GO:0005886 C:plasma membrane
GO:0005254 F:chloride channel activity
GO:0002543 P:activation of blood coagulation via clotting cascade
GO:0097045 P:phosphatidylserine exposure on blood platelet

References (7)

[1] “The finished DNA sequence of human chromosome 12.”  Scherer S.E.et.al.   16541075
[2] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[3] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[4] “Identification and characterization of TMEM16E and TMEM16F genes in silico.”  Katoh M.et.al.   15067359
[5] “TMEM16A confers receptor-activated calcium-dependent chloride conductance.”  Yang Y.D.et.al.   18724360
[6] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218
[7] “Calcium-dependent phospholipid scrambling by TMEM16F.”  Suzuki J.et.al.   21107324

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FASTA formatted sequence
1:	MKKMSRNVLL QMEEEEDDDD GDIVLENLGQ TIVPDLGSLE SQHDFRTPEF EEFNGKPDSL 
61:	FFNDGQRRID FVLVYEDESR KETNKKGTNE KQRRKRQAYE SNLICHGLQL EATRSVLDDK 
121:	LVFVKVHAPW EVLCTYAEIM HIKLPLKPND LKNRSSAFGT LNWFTKVLSV DESIIKPEQE 
181:	FFTAPFEKNR MNDFYIVDRD AFFNPATRSR IVYFILSRVK YQVINNVSKF GINRLVNSGI 
241:	YKAAFPLHDC KFRRQSEDPS CPNERYLLYR EWAHPRSIYK KQPLDLIRKY YGEKIGIYFA 
301:	WLGYYTQMLL LAAVVGVACF LYGYLNQDNC TWSKEVCHPD IGGKIIMCPQ CDRLCPFWKL 
361:	NITCESSKKL CIFDSFGTLV FAVFMGVWVT LFLEFWKRRQ AELEYEWDTV ELQQEEQARP 
421:	EYEARCTHVV INEITQEEER IPFTAWGKCI RITLCASAVF FWILLIIASV IGIIVYRLSV 
481:	FIVFSAKLPK NINGTDPIQK YLTPQTATSI TASIISFIII MILNTIYEKV AIMITNFELP 
541:	RTQTDYENSL TMKMFLFQFV NYYSSCFYIA FFKGKFVGYP GDPVYWLGKY RNEECDPGGC 
601:	LLELTTQLTI IMGGKAIWNN IQEVLLPWIM NLIGRFHRVS GSEKITPRWE QDYHLQPMGK 
661:	LGLFYEYLEM IIQFGFVTLF VASFPLAPLL ALVNNILEIR VDAWKLTTQF RRLVPEKAQD 
721:	IGAWQPIMQG IAILAVVTNA MIIAFTSDMI PRLVYYWSFS VPPYGDHTSY TMEGYINNTL 
781:	SIFKVADFKN KSKGNPYSDL GNHTTCRYRD FRYPPGHPQE YKHNIYYWHV IAAKLAFIIV 
841:	MEHVIYSVKF FISYAIPDVS KRTKSKIQRE KYLTQKLLHE NHLKDMTKNM GVIAERMIEA 
901:	VDNNLRPKSE