Reviewed,
UniProtKB/Swiss-Prot P13569 (CFTR_HUMAN)
Last modified
November 25, 2008.
Version 130.
History...
Clusters with 100%,
90%,
50% identity |
Documents (8) |
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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 |
| ||||
| 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 | |
| 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
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. | ||||||

Clusters with