Cystic Fibrosis Mutation Database: CFTR Domains

The cystic fibrosis transmembrane conductance regulator (CFTR) is a 1480 amino acid membrane bound glycoprotein with a molecular mass of 170,000. It is a member of the ATP binding cassette (ABC)superfamily of proteins. The protein is comprised of two, six span membrane bound regions each connected to a nuclear binding factor which binds ATP. Between these two units is an R-domain which is comprised of many charged amino acids. The R-domain is a unique feature of CFTR within the ABC superfamily.

Put your mouse over the domain region in the following graph to view the summary of that domain, click to view the details.

19 % of the CFTR protein make up the twelve transmembrane domains (M1 - M12). These domains have been shown to be comprised of typical a-helical secondary structure. Many of the residues within these regions form the channel lining residues and have a major role in the regulation of pore function. Six positively charged residues within the transmembrane domains [K95 (M1), R134 (M2), R334 (M6), K335 (M6), R347 (M6) and R1030 (M10] that are well conserved across species. Two of these are associated with mutations causing CF, R334Q/W and R347C/H/L/P.

The mutations happenning in MSD11 domain:

cDNA Name	Protein Name	Legacy Name	Region	Description	Consequence
c.3535_3538delACCA	p.Thr1179AsnfsX12	3667del4	exon 22	deletion of 4 bp from 3667	frameshift
c.3535_3536insTCAA	p.Thr1179IlefsX17	3667ins4	exon 22	insertion of TCAA after 3667	frameshift
c.3540delA	p.Lys1180AsnfsX12	3670delA	exon 22	deletion of A at 3670	frameshift
c.3546C>G	p.Tyr1182X	Y1182X	exon 22	C to G at 3678	Tyr to Stop at 1182
c.3556C>T	p.Gln1186X	Q1186X	exon 22	C to T at 3688	Gln to Stop at 1186
c.3558A>G		Q1186Q (3690A/G)	exon 22	A or G at 3690	sequence variation
c.3564G>A		3696G/A	exon 21	G to A at 3696	No change to Ser at 1188
c.3569T>A	p.Val1190Asp	V1190D	exon 22	T to A at 3701	Val to Asp at 1190
c.3584A>C	p.Asn1195Thr	N1195T	exon 22	A to C at 3716	Asn to Thr at 1195
c.3587C>G	p.Ser1196X	S1196X	exon 22	C to G at 3719	Ser to Stop at 1196
c.3592delG	p.Val1198X	3724delG	exon 22	deletion of G at 3724	frameshift
c.3594G>T		3726G/T	exon 22	G or T at 3726	sequence variation