Reviewed, UniProtKB/Swiss-Prot P13569 (CFTR_HUMAN)

Names and origin

Protein names

Recommended name:
    Cystic fibrosis transmembrane conductance regulator
      Short name=CFTR
Alternative name(s):
    cAMP-dependent chloride channel
    ATP-binding cassette transporter sub-family C member 7

Gene names

Name:	CFTR
Synonyms:	ABCC7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1480 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter.
Subunit structure	Interacts with SHANK2 By similarity. Interacts with SLC9A3R1, MYO6 and GOPC. Interacts with SLC4A7 through SLC9A3R1.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Found on the surface of the epithelial cells that line the lungs and other organs.
Domain	The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, SLC9A3R1/EBP50 complex.
Post-translational modification	Phosphorylated; activates the channel. It is not clear whether PKC phosphorylation itself activates the channel or permits activation by phosphorylation at PKA sites.
Involvement in disease	Defects in CFTR are the cause of cystic fibrosis (CF) [MIM:219700]; also known as mucoviscidosis. CF is the most common genetic disease in the Caucasian population, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. CF is a common generalized disorder of exocrine gland function which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. Defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]. CBAVD is an important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens.
Sequence similarities	Belongs to the ABC transporter family. CFTR transporter (TC 3.A.1.202) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane
Ligand	ATP-binding Chloride Nucleotide-binding
Molecular function	Chloride channel Ionic channel
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	ion transport Inferred from electronic annotation. Source: InterPro respiratory gaseous exchange Traceable author statement. Source: ProtInc
Cellular component	apical plasma membrane Ref.12 Inferred from direct assay. Source: UniProtKB basolateral plasma membrane Ref.10 Non-traceable author statement. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Ref.1 Traceable author statement. Source: ProtInc ATP-binding and phosphorylation-dependent chloride channel activity Traceable author statement. Source: ProtInc PDZ domain binding Ref.10 Inferred from direct assay. Source: UniProtKB channel-conductance-controlling ATPase activity Ref.10 Non-traceable author statement. Source: UniProtKB chloride ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCAP31	P51572	2	EBI-349854,EBI-77683
DERL1	Q9BUN8	1	EBI-349854,EBI-398977
GOPC	Q9HD26	1	EBI-349854,EBI-349832
LPAR2	Q9HBW0	1	EBI-349854,EBI-765995
PDZK1	Q5T2W1	1	EBI-349854,EBI-349819
RNF5	Q99942	1	EBI-349854,EBI-348482
SLC9A3R1	O14745	1	EBI-349854,EBI-349787
SLC9A3R2	Q15599	1	EBI-349854,EBI-1149760

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P13569-1)

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.

Isoform 2 (identifier: P13569-2)

The sequence of this isoform differs from the canonical sequence as follows:
     404-464: Missing.

Notes: Skipping of exon 9: a high number of TG repeats and a low number of T repeats at the intron 8-exon 9 junction favor exon skipping. Causes congenital bilateral absence of the vas deferens (CBAVD).

Isoform 3 (identifier: P13569-3)

The sequence of this isoform differs from the canonical sequence as follows:
     589-605: SCVCKLMANKTRILVTS → RRRCSCLLDRNKKTIF
     606-1480: Missing.

Notes: Skipping of the first 248 nucleotides of exon 13, caused by mutation of the exon splicing exon (ESE) in exon 13. Causes cystic fibrosis (CF).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1480	1480	Cystic fibrosis transmembrane conductance regulator		PRO_0000093419
Regions
	Topological domain	1 – 80	80	Cytoplasmic Potential
	Transmembrane	81 – 103	23	1 Potential
	Topological domain	104 – 117	14	Extracellular Potential
	Transmembrane	118 – 138	21	2 Potential
	Topological domain	139 – 194	56	Cytoplasmic Potential
	Transmembrane	195 – 215	21	3 Potential
	Topological domain	216 – 220	5	Extracellular Potential
	Transmembrane	221 – 241	21	4 Potential
	Topological domain	242 – 307	66	Cytoplasmic Potential
	Transmembrane	308 – 328	21	5 Potential
	Topological domain	329 – 330	2	Extracellular Potential
	Transmembrane	331 – 350	20	6 Potential
	Topological domain	351 – 859	509	Cytoplasmic Potential
	Transmembrane	860 – 880	21	7 Potential
	Topological domain	881 – 911	31	Extracellular Potential
	Transmembrane	912 – 932	21	8 Potential
	Topological domain	933 – 990	58	Cytoplasmic Potential
	Transmembrane	991 – 1011	21	9 Potential
	Topological domain	1012 – 1013	2	Extracellular Potential
	Transmembrane	1014 – 1034	21	10 Potential
	Topological domain	1035 – 1102	68	Cytoplasmic Potential
	Transmembrane	1103 – 1123	21	11 Potential
	Topological domain	1124 – 1128	5	Extracellular Potential
	Transmembrane	1129 – 1149	21	12 Potential
	Topological domain	1150 – 1480	331	Cytoplasmic Potential
	Domain	81 – 365	285	ABC transmembrane type-1 1
	Domain	423 – 646	224	ABC transporter 1
	Domain	859 – 1155	297	ABC transmembrane type-1 2
	Domain	1210 – 1443	234	ABC transporter 2
	Nucleotide binding	458 – 465	8	ATP 1 Potential
	Nucleotide binding	1244 – 1251	8	ATP 2 Potential
	Motif	1478 – 1480	3	PDZ-binding
Amino acid modifications
	Modified residue	515	1	Phosphotyrosine
	Modified residue	660	1	Phosphoserine; by PKA
	Modified residue	686	1	Phosphoserine; by PKC
	Modified residue	700	1	Phosphoserine; by PKA
	Modified residue	712	1	Phosphoserine; by PKA
	Modified residue	737	1	Phosphoserine; by PKA
	Modified residue	753	1	Phosphoserine; by PKA
	Modified residue	768	1	Phosphoserine; by PKA
	Modified residue	790	1	Phosphoserine; by PKC
	Modified residue	795	1	Phosphoserine; by PKA
	Modified residue	813	1	Phosphoserine; by PKA
	Glycosylation	894	1	N-linked (GlcNAc...)
	Glycosylation	900	1	N-linked (GlcNAc...)
Natural variations
	Alternative sequence	404 – 464	61	Missing in isoform 2.		VSP_022123
	Alternative sequence	589 – 605	17	SCVCK…ILVTS → RRRCSCLLDRNKKTIF in isoform 3.		VSP_022124
	Alternative sequence	606 – 1480	875	Missing in isoform 3.		VSP_022125
	Natural variant	13	1	S → F in CF.		VAR_000101
	Natural variant	31	1	R → C: dbSNP rs1800073.		VAR_000102
	Natural variant	31	1	R → L in CF.		VAR_000103
	Natural variant	42	1	S → F in CF.		VAR_000104
	Natural variant	44	1	D → G in CF.		VAR_000105
	Natural variant	44	1	D → V: dbSNP rs1800074.		VAR_000106
	Natural variant	50	1	S → Y in CBAVD.		VAR_000107
	Natural variant	57	1	W → G in CF.		VAR_000108
	Natural variant	67	1	P → L in CF.		VAR_000109
	Natural variant	74	1	R → W in CF.		VAR_000110
	Natural variant	75	1	R → Q: dbSNP rs1800076.		VAR_000111
	Natural variant	85	1	G → E in CF.		VAR_000112
	Natural variant	87	1	F → L in CF.		VAR_000113
	Natural variant	91	1	G → R in CF.		VAR_000114
	Natural variant	92	1	E → K in CF.		VAR_000115
	Natural variant	98	1	Q → R in CF.		VAR_000116
	Natural variant	105	1	I → S in CF.		VAR_000117
	Natural variant	109	1	Y → C in CF.		VAR_000118
	Natural variant	110	1	D → H in CF.		VAR_000119
	Natural variant	111	1	P → L in CBAVD.		VAR_000120
	Natural variant	117	1	R → C in CF.		VAR_000121
	Natural variant	117	1	R → H in CF and CBAVD.		VAR_000122
	Natural variant	117	1	R → L in CF.		VAR_000123
	Natural variant	117	1	R → P in CF.		VAR_000124
	Natural variant	120	1	A → T in CF.		VAR_000125
	Natural variant	138	1	L → P: dbSNP rs1800078.		VAR_009895
	Natural variant	139	1	H → R in CF.		VAR_000126
	Natural variant	141	1	A → D in CF.		VAR_000127
	Natural variant	148	1	I → T in CF. dbSNP rs35516286.		VAR_000128
	Natural variant	149	1	G → R in CBAVD.		VAR_000129
	Natural variant	170	1	R → H: dbSNP rs1800079.		VAR_009896
	Natural variant	178	1	G → R in CF.		VAR_000130
	Natural variant	182	1	S → G: dbSNP rs1800080.		VAR_009897
	Natural variant	192	1	Missing in CF.		VAR_000131
	Natural variant	193	1	E → K in CBAVD and CF.