Protein Details: Cystic fibrosis transmembrane conductance regulator

Protein ID

ICDB_Pro_0484

Protein Name

Cystic fibrosis transmembrane conductance regulator

Gene Name

Cftr; Abcc7

Organism

Rattus norvegicus (Rat)

Length

1476 amino acids

AlphaFoldDB

AF-P34158-F1-model_v4.pdb

Function

Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane (By similarity). Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer. Modulates the activity of the epithelial sodium channel (ENaC) complex; in part by regulating the cell surface expression of the ENaC complex. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1 (By similarity). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (By similarity).

Sequence

MQKSPLEKASFISKLFFSWTTPILRKGYRHHLELSDIYQAPSSDSADHLSEKLEREWDREQASKKKPQLIHALRRCFVWRFVFYGVLLYLGEVTKAVQPVLLGRIIASYDPDNTEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQLISLLSNNLNKFDEGLALAHFIWIAPLQVVLLMGLLWDLLQFSAFCGLGLLIVLVIFQAILGKMMVKYRDKRAAKINERLVITSEVIDNIYSVKAYCWESAMEKIIESLREEELKMTRRSAYMRFFTSSAFFFSGFFVVFLSVLPYTVINGIVLRKIFTTISFCIVLRMSVTRQFPTAVQIWYDSLGMIRKIQDFLQTQEYKVLEYNLMFTGLVMENVTAFWEEGFQELLEKVQLNNDDRKTSNGENHLSFSHLCLVGNPVLKNINLNIKKGEMLAITGSTGAGKTSLLMLILGELEASEGIIKHSGRVSFSSQISWIMPGTIKENIIFGVSYDEYRYKSVVKACQLQEDITKFAEQDNTVLGEGGVTLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEEQIFESCVCKLMASKTRILVTSKMEQLKKADKILILHEGSSYFYGTFSELQSLRPDFSSKLMGYDTFDQFTEERRSSILTETLRRFSVDDASTTWNKAKQSFRQTGEFGEKRKNSILSSFSSVKKISIVQKTPLSIEGESDDLQERRLSLVPDSEHGEAALPRSNMITAGPTFPGRRRQSVLDLMTFTPSSVSSSLQRTRASIRKISLAPRISLKEEDIYSRRLSQDSTLNITEEINEEDLKECFFDDMVKIPTVTTWNTYLRYFTLHRGLFAVLIWCVLVFLVEVAASLFVLWLLKNNPVNGGNNGTKIANTSYVVVITSSSFYYIFYIYVGVADTLLALSLFRGLPLVHTLITASKILHRKMLHSILHAPMSTFNKLKAGGILNRFSKDIAILDDFLPLTIFDFIQLLFIVVGAIIVVSALQPYIFLATVPGLAVFILLRAYFLHTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFRRQTYFETLFHKALNLHTANWFMYLATLRWFQMRIDMIFVLFFIVVTFISILTTGEGEGTTGIILTLAMNIMSTLQWAVNSSIDTDSLMRSVSRVFKFIDIQTEESICTKIMKELHSEDSPNALVIKNEHVKKCDTWPSGGEMVVKDLTVKYVDDGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRMLNIKGEIQIDGVSWNSMTLQEWRKAFGVITQKVFIFSGTFRQNLDPNGKWRDEEIWKVADQVGLKSVIEQFPGQLNFTLVDGGYVLSHGHKQLMCLARSVLSKAKIILLDEPSANLDPITYQVIRRVLRQAFAGCTVVLCEHRIEAMLDCQRFLVIEQGNVWQYESLQALLSEKSVFQRALSSSEKMKLFHGRHSSKQKPRTQITAVKEETEEEVQETRL

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

BINDING 401; /ligand="ATP"; BINDING 458..465; /ligand="ATP"; BINDING 458..465; /ligand="ATP"; BINDING 493; /ligand="ATP"; BINDING 1215; /ligand="ATP"; BINDING 1240..1247; /ligand="ATP"; BINDING 1240..1247; /ligand="ATP"

Disease

Location

Detected in epithelial cells in nasopharynx; submandibular gland; pancreas and ileum (at protein level) (PubMed:12519745). Expressed in the epididymis (PubMed:30659401). In the caput section of the epididymis; expressed uniformly on both the luminal and basolateral sides of the ducts and on sperm in the caput lumen (at protein level) (PubMed:30659401). In the caput section of the epididymis; expressed uniformly on both the luminal and basolateral sides of the ducts and on sperm in the caput lumen (at protein level) (PubMed:30659401). In the caput section of the epididymis; expressed uniformly on both the luminal and basolateral sides of the ducts and on sperm in the caput lumen (at protein level) (PubMed:30659401). In the cauda; detected along the luminal border but not continuously and is also expressed on the basolateral surface (PubMed:30659401). Within the caudal lumen; detected on sperm (PubMed:30659401).

DOI ID

10.1038/nature01858; 10.1093/hmg/3.7.1089; 10.1016/s0888-7543(05)80107-7; 10.1074/jbc.m110177200; 10.1152/ajpcell.00227.2002; 10.1074/jbc.m312871200; 10.1038/ncomms1871; 10.1007/s10735-018-9759-2; 10.1007/s10735-019-09813-3

RefSeq

NP_113694.1