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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, and promote assembly of the tenase and prothrombinase complexes involved in blood coagulation (Fujii et al. 2015). 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, and promote assembly of the tenase and prothrombinase complexes involved in blood coagulation (Fujii et al. 2015). 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