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Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi458 – 465ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1245 – 1252ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Hydrolase, Ion channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cystic fibrosis transmembrane conductance regulator
Short name:
CFTR
Alternative name(s):
ATP-binding cassette sub-family C member 7
Channel conductance-controlling ATPase (EC:3.6.3.49)
cAMP-dependent chloride channel
Gene namesi
Name:CFTR
Synonyms:ABCC7
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Unplaced

Subcellular locationi

  • Early endosome membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Cell membrane By similarity; Multi-pass membrane protein Sequence analysis

  • Note: In epithelial cells, detected on the apical side, but not associated with cilia.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 80CytoplasmicSequence analysisAdd BLAST80
Transmembranei81 – 101Helical; Name=1PROSITE-ProRule annotationAdd BLAST21
Topological domaini102 – 117ExtracellularSequence analysisAdd BLAST16
Transmembranei118 – 138Helical; Name=2PROSITE-ProRule annotationAdd BLAST21
Topological domaini139 – 194CytoplasmicSequence analysisAdd BLAST56
Transmembranei195 – 215Helical; Name=3PROSITE-ProRule annotationAdd BLAST21
Topological domaini216 – 220ExtracellularSequence analysis5
Transmembranei221 – 241Helical; Name=4PROSITE-ProRule annotationAdd BLAST21
Topological domaini242 – 307CytoplasmicSequence analysisAdd BLAST66
Transmembranei308 – 328Helical; Name=5PROSITE-ProRule annotationAdd BLAST21
Topological domaini329 – 331ExtracellularSequence analysis3
Transmembranei332 – 350Helical; Name=6PROSITE-ProRule annotationAdd BLAST19
Topological domaini351 – 859CytoplasmicSequence analysisAdd BLAST509
Transmembranei860 – 880Helical; Name=7PROSITE-ProRule annotationAdd BLAST21
Topological domaini881 – 911ExtracellularSequence analysisAdd BLAST31
Transmembranei912 – 932Helical; Name=8PROSITE-ProRule annotationAdd BLAST21
Topological domaini933 – 990CytoplasmicSequence analysisAdd BLAST58
Transmembranei991 – 1011Helical; Name=9PROSITE-ProRule annotationAdd BLAST21
Topological domaini1012 – 1013ExtracellularSequence analysis2
Transmembranei1014 – 1034Helical; Name=10PROSITE-ProRule annotationAdd BLAST21
Topological domaini1035 – 1102CytoplasmicSequence analysisAdd BLAST68
Transmembranei1103 – 1123Helical; Name=11PROSITE-ProRule annotationAdd BLAST21
Topological domaini1124 – 1126ExtracellularSequence analysis3
Transmembranei1127 – 1147Helical; Name=12PROSITE-ProRule annotationAdd BLAST21
Topological domaini1148 – 1481CytoplasmicSequence analysisAdd BLAST334

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000934221 – 1481Cystic fibrosis transmembrane conductance regulatorAdd BLAST1481

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi524S-palmitoyl cysteineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei660PhosphoserineBy similarity1
Modified residuei686PhosphoserineBy similarity1
Cross-linki688Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei700PhosphoserineBy similarity1
Modified residuei712PhosphoserineBy similarity1
Modified residuei717PhosphothreonineBy similarity1
Modified residuei737PhosphoserineBy similarity1
Modified residuei753PhosphoserineBy similarity1
Modified residuei768PhosphoserineBy similarity1
Modified residuei790PhosphoserineBy similarity1
Modified residuei795PhosphoserineBy similarity1
Modified residuei813PhosphoserineBy similarity1
Glycosylationi894N-linked (GlcNAc...)Sequence analysis1
Glycosylationi900N-linked (GlcNAc...)Sequence analysis1
Lipidationi1396S-palmitoyl cysteineBy similarity1
Modified residuei1445PhosphoserineBy similarity1
Modified residuei1457PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes, enhances its endocytic recycling. Ubiquitinated by RNF185 during ER stress (By similarity).By similarity
Phosphorylated; activates the channel. It is not clear whether PKC phosphorylation itself activates the channel or permits activation by phosphorylation at PKA sites. Phosphorylated by AMPK (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Interacts with MYO6 and GOPC. Interacts with SLC4A7 through SLC9A3R1. Interacts with SHANK2 (By similarity). Found in a complex with MYO5B and RAB11A (By similarity). Interacts with ANO1 (By similarity). Interacts with SLC26A3, SLC26A6 and SLC9A3R1. Interacts with SLC26A8. Interacts with AHCYL1; the interaction increases CFTR activity (By similarity).By similarity

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000014766.

Structurei

3D structure databases

ProteinModelPortaliQ00553.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 365ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST285
Domaini423 – 646ABC transporter 1PROSITE-ProRule annotationAdd BLAST224
Domaini859 – 1155ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST297
Domaini1211 – 1444ABC transporter 2PROSITE-ProRule annotationAdd BLAST234

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1479 – 1481PDZ-binding3

Domaini

The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, SLC9A3R1/EBP50 complex.By similarity

Sequence similaritiesi

Contains 2 ABC transmembrane type-1 domains.PROSITE-ProRule annotation
Contains 2 ABC transporter domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG004169.
InParanoidiQ00553.
KOiK05031.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR009147. CFTR/ABCC7.
IPR025837. CFTR_reg_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR24223:SF19. PTHR24223:SF19. 3 hits.
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
PF14396. CFTR_R. 1 hit.
[Graphical view]
PRINTSiPR01851. CYSFIBREGLTR.
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
TIGRFAMsiTIGR01271. CFTR_protein. 1 hit.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q00553-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRSPLEKAS VVSKLFFSWT RPILRKGYRQ RLELSDIYQI PSADSADNLS
60 70 80 90 100
EKLEREWDRE LASKKNPKLI NALRRCFFWR FMFYGILLYL GEVTKAVQPL
110 120 130 140 150
LLGRIIASYD PDNKEERSIA IYLGIGLCLL FIVRTLLLHP AIFGLHHIGM
160 170 180 190 200
QMRIAMFSLI YKKTLKLSSR VLDKISIGQL VSLLSNNLNK FDEGLALAHF
210 220 230 240 250
VWIVPLQVAL LMGLIWELLQ ASAFCGLGFL IVLALFQAGL GRMMMKYRDQ
260 270 280 290 300
RAGKINERLV ITSEMIENIQ SVKAYCWEEA MEKMIENLRQ TELKLTRKAA
310 320 330 340 350
YVRYFNSSAF FFSGFFVVFL SVLPYALIKG IVLRKIFTTI SFCIVLRMAV
360 370 380 390 400
TRQFPWAVQT WYDSLGAINK IQDFLQKQEY KTLEYNLTTT EVVMENVTAF
410 420 430 440 450
WEEGFGELFE KAKQNNSNRK TSNDDDSLFF SNFSLLGTPV LKDINFKIER
460 470 480 490 500
GQLLAVAGST GAGKTSLLMM IMGELEPSEG KIKHSGRISF CSQFSWIMPG
510 520 530 540 550
TIKENIIFGV SYDEYRYRSV INACQLEEDI SKFAEKDNIV LGEGGITLSG
560 570 580 590 600
GQRARISLAR AVYKDADLYL LDSPFGYLDV LTEKEIFESC VCKLMANKTR
610 620 630 640 650
ILVTSKMEHL KKADKILILH EGSSYFYGTF SELQNLRPDF SSKLMGYDSF
660 670 680 690 700
DQFSAERRNS ILTETLRRFS LEGDAPVSWT ETKKQSFKQT GEFGEKRKNS
710 720 730 740 750
ILNPINSIRK FSIVQKTPLQ MNGIEEDSDE PLERRLSLVP DSEQGEVILP
760 770 780 790 800
RISVISTGPT LQARRRQSVL NLMTHSVNQG QSIHRKTAAS TRKVSLAPQA
810 820 830 840 850
NLTELDIYSR RLSQETGLEI SEEINEEDLK ECFFDDMESI PAVTTWNTYL
860 870 880 890 900
RYITVHKSLI FVLIWCLVIF LAEVAASLVV LWFLGNTPPQ DKGNSTYSRN
910 920 930 940 950
NSYAVIITRT SSYYVFYIYV GVADTLLAMG FFRGLPLVHT LITVSKILHH
960 970 980 990 1000
KMLHSVLQAP MSTLNTLKAG GILNRFSKDI AILDDLLPLT IFDFIQLLLI
1010 1020 1030 1040 1050
VIGAIAVVAV LQPYIFVATV PVIVAFIMLR AYFLQTSQQL KQLESEGRSP
1060 1070 1080 1090 1100
IFTHLVTSLK GLWTLRAFGR QPYFETLFHK ALNLHTANWF LYLSTLRWFQ
1110 1120 1130 1140 1150
MRIEMIFVIF FIAVTFISIL TTGEGEGTVG IILTLAMNIM STLQWAVNSS
1160 1170 1180 1190 1200
IDVDSLMRSV SRVFKFIDMP TEEGKPTRST KPYKNGQLSK VMVIENSHVK
1210 1220 1230 1240 1250
KDDIWPSGGQ MTVKDLTAKY TEGGNPILEN ISFSISPGQR VGLLGRTGSG
1260 1270 1280 1290 1300
KSTLLSAFLR LLNTEGEIQI DGVSWDSITL QQWRKAFGVI PQKVFIFSGT
1310 1320 1330 1340 1350
FRKNLDPYEQ WSDQEIWKVA DEVGLRSVIE QFPGKLDFVL VDGGCVLSHG
1360 1370 1380 1390 1400
HKQLMCLARS VLSKAKILLL DEPSAHLDPV TYQIIRRTLK QAFADCTVIL
1410 1420 1430 1440 1450
CEHRIEAMLE CQQFLVIEEN KVRQYDSIQK LLNERSLFRQ AISPSDRVKL
1460 1470 1480
FPHRNSSKCK TQPQIAALKE ETEEEVQDTR L
Length:1,481
Mass (Da):168,489
Last modified:September 27, 2005 - v2
Checksum:iA9AE0F3BB1197570
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti601 – 603ILV → TTL in AAA36839 (PubMed:1719001).Curated3
Sequence conflicti676P → G in AAA36839 (PubMed:1719001).Curated1
Sequence conflicti741D → Y in AAA36839 (PubMed:1719001).Curated1
Sequence conflicti769V → E in AAA36839 (PubMed:1719001).Curated1
Sequence conflicti833F → L in AAC14011 (PubMed:9530627).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013753 mRNA. Translation: AAC14011.1.
AF016950
, AF016924, AF016925, AF016926, AF016927, AF016928, AF016929, AF016930, AF016931, AF016932, AF016933, AF016934, AF016935, AF016936, AF016937, AF016938, AF016939, AF016940, AF016941, AF016942, AF016943, AF016944, AF016945, AF016946, AF016947, AF016948, AF016949 Genomic DNA. Translation: AAC14012.1.
M96680 Genomic DNA. Translation: AAA36839.1.
PIRiC39323.
RefSeqiNP_001028110.1. NM_001032938.1.
UniGeneiMmu.3437.

Genome annotation databases

GeneIDi574346.
KEGGimcc:574346.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013753 mRNA. Translation: AAC14011.1.
AF016950
, AF016924, AF016925, AF016926, AF016927, AF016928, AF016929, AF016930, AF016931, AF016932, AF016933, AF016934, AF016935, AF016936, AF016937, AF016938, AF016939, AF016940, AF016941, AF016942, AF016943, AF016944, AF016945, AF016946, AF016947, AF016948, AF016949 Genomic DNA. Translation: AAC14012.1.
M96680 Genomic DNA. Translation: AAA36839.1.
PIRiC39323.
RefSeqiNP_001028110.1. NM_001032938.1.
UniGeneiMmu.3437.

3D structure databases

ProteinModelPortaliQ00553.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000014766.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi574346.
KEGGimcc:574346.

Organism-specific databases

CTDi1080.

Phylogenomic databases

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG004169.
InParanoidiQ00553.
KOiK05031.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR009147. CFTR/ABCC7.
IPR025837. CFTR_reg_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR24223:SF19. PTHR24223:SF19. 3 hits.
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
PF14396. CFTR_R. 1 hit.
[Graphical view]
PRINTSiPR01851. CYSFIBREGLTR.
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
TIGRFAMsiTIGR01271. CFTR_protein. 1 hit.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCFTR_MACMU
AccessioniPrimary (citable) accession number: Q00553
Secondary accession number(s): O62668, O62673
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: September 27, 2005
Last modified: October 5, 2016
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.