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1.A.48 The Anion Channel Tweety (Tweety) Family

The Tweety family is a newly identified family of anion channel proteins found in animals and plants. These proteins contain about 500-1200 aas and 5 or 6 TMSs in an arrangement: 2 + 2 + 1, with an extra N-terminal TMS present in some plant homologues (e.g., NP_178935). They produce large conductance chloride (maxi-Cl-) currents.

'Tweety' is a gene located in the Drosophila melanogaster 'flightless' locus. It has three human homologues (hTTYH1-3) which are also novel maxi-Cl- channel proteins (Suzuki and Mizuno, 2004). He et al., (2008) provided evidence for a structure for Tweety family proteins which incorporates five membrane-spanning domains with a topology at the cell surface in which the N-terminus is located extracellularly and the C-terminus cytoplasmically. N-Glycosylation is important, but not essential, in the processing of members of the Tweety family. Incomplete N-glycosylation mediates reduced expression and increased ubiquitination (He et al., 2008).

hTTYH3 mRNA is distributed in excitable tissues. Positively charged amino acyl residues in the pore contribute to anion selectivity. The hTTYH3 single channel shows 26 picosiemen linear current voltage, complex kinetics and sensitivity to 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid. It shows permeability in the order I- > Br- > Cl-. This channel and hTTYH2 encode ionomycin-induced maxi-Cl- channels, but hTTYH1 encodes a Ca2+-independent, swelling-activated maxi-Cl- channel (Suzuki and Mizuno, 2004).

Homologues of Tweety are found in vertebrates, insects, worms and probably plants. They are prevalent in animals but scarce in plants. A search is in progress to identify homologues elsewhere.

References associated with 1.A.48 family:

He, Y., A.J. Ramsay, M.L. Hunt, A.K. Whitbread, S.A. Myers, and J.D. Hooper. (2008). N-glycosylation analysis of the human Tweety family of putative chloride ion channels supports a penta-spanning membrane arrangement: impact of N-glycosylation on cellular processing of Tweety homologue 2 (TTYH2). Biochem. J. 412: 45-55. 18260827
Suzuki, M. and A. Mizuno. (2004). A novel human Cl- channel family related to Drosophila flightless locus. J. Biol. Chem. 279: 22461-22468. 15010458