Protein Details: Cystic fibrosis transmembrane conductance regulator

Protein ID

ICDB_Pro_0441

Protein Name

Cystic fibrosis transmembrane conductance regulator

Gene Name

Cftr; Abcc7

Organism

Mus musculus (Mouse)

Length

1476 amino acids

AlphaFoldDB

AF-P26361-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 . 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 .

Sequence

MQKSPLEKASFISKLFFSWTTPILRKGYRHHLELSDIYQAPSADSADHLSEKLEREWDREQASKKNPQLIHALRRCFFWRFLFYGILLYLGEVTKAVQPVLLGRIIASYDPENKVERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHRIGMQMRTAMFSLIYKKTLKLSSRVLDKISIGQLVSLLSNNLNKFDEGLALAHFIWIAPLQVTLLMGLLWDLLQFSAFCGLGLLIILVIFQAILGKMMVKYRDQRAAKINERLVITSEIIDNIYSVKAYCWESAMEKMIENLREVELKMTRKAAYMRFFTSSAFFFSGFFVVFLSVLPYTVINGIVLRKIFTTISFCIVLRMSVTRQFPTAVQIWYDSFGMIRKIQDFLQKQEYKVLEYNLMTTGIIMENVTAFWEEGFGELLEKVQQSNGDRKHSSDENNVSFSHLCLVGNPVLKNINLNIEKGEMLAITGSTGSGKTSLLMLILGELEASEGIIKHSGRVSFCSQFSWIMPGTIKENIIFGVSYDEYRYKSVVKACQLQQDITKFAEQDNTVLGEGGVTLSGGQRARISLARAVYKDADLYLLDSPFGYLDVFTEEQVFESCVCKLMANKTRILVTSKMEHLRKADKILILHQGSSYFYGTFSELQSLRPDFSSKLMGYDTFDQFTEERRSSILTETLRRFSVDDSSAPWSKPKQSFRQTGEVGEKRKNSILNSFSSVRKISIVQKTPLCIDGESDDLQEKRLSLVPDSEQGEAALPRSNMIATGPTFPGRRRQSVLDLMTFTPNSGSSNLQRTRTSIRKISLVPQISLNEVDVYSRRLSQDSTLNITEEINEEDLKECFLDDVIKIPPVTTWNTYLRYFTLHKGLLLVLIWCVLVFLVEVAASLFVLWLLKNNPVNSGNNGTKISNSSYVVIITSTSFYYIFYIYVGVADTLLALSLFRGLPLVHTLITASKILHRKMLHSILHAPMSTISKLKAGGILNRFSKDIAILDDFLPLTIFDFIQLVFIVIGAIIVVSALQPYIFLATVPGLVVFILLRAYFLHTAQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFRRQTYFETLFHKALNLHTANWFMYLATLRWFQMRIDMIFVLFFIVVTFISILTTGEGEGTAGIILTLAMNIMSTLQWAVNSSIDTDSLMRSVSRVFKFIDIQTEESMYTQIIKELPREGSSDVLVIKNEHVKKSDIWPSGGEMVVKDLTVKYMDDGNAVLENISFSISPGQRVGLLGRTGSGKSTLLSAFLRMLNIKGDIEIDGVSWNSVTLQEWRKAFGVITQKVFIFSGTFRQNLDPNGKWKDEEIWKVADEVGLKSVIEQFPGQLNFTLVDGGYVLSHGHKQLMCLARSVLSKAKIILLDEPSAHLDPITYQVIRRVLKQAFAGCTVILCEHRIEAMLDCQRFLVIEESNVWQYDSLQALLSEKSIFQQAISSSEKMRFFQGRHSSKHKPRTQITALKEETEEEVQETRL

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

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

Disease

Location

Expressed in the epididymis (at protein level) (PubMed:30659401). In the initial segment of the epididymis; detected on both the luminal and basolateral sides of the ducts where it is expressed in the duct columnar cells as well as in the interstitial smooth muscle cells (PubMed:30659401). Expressed in sperm in the caput (PubMed:30659401). Expressed in sperm in the caput (PubMed:30659401). Expressed in sperm in the caput (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). Isoform 1: Expressed in a variety of epithelial tissues including colon; kidney; lung; small intestine; pancreatic duct and testis (PubMed:7691356). Isoform 2: Expressed only in testis (PubMed:7691356). Isoform 3: Expressed only in testis (PubMed:7691356)..

DOI ID

10.1016/0888-7543(91)90312-3; 10.1016/0888-7543(91)90434-g; 10.1073/pnas.97.3.1172; 10.1093/hmg/3.7.1089; 10.1038/ng0893-426; 10.1038/ng0593-35; 10.1172/jci36983; 10.1016/j.cell.2010.12.001; 10.1073/pnas.0902661107; 10.1095/biolreprod.111.094037; 10.1053/j.gastro.2013.03.047; 10.1126/science.aad5589; 10.1016/j.cell.2011.07.021; 10.1007/s10735-019-09813-3; 10.1038/sj.emboj.7600040; 10.1038/nsmb881; 10.1016/j.cell.2011.11.023

RefSeq

NP_066388.1 [P26361-1]; XP_006505040.1; XP_006505041.1

Feature