SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00001881 
UniProt Accession
Theoretical PI
8.93  
Molecular Weight
167830 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Cftr 
Gene Synonyms/Alias
Abcc7 
Protein Name
Cystic fibrosis transmembrane conductance regulator 
Protein Synonyms/Alias
CFTR ATP-binding cassette sub-family C member 7; Channel conductance-controlling ATPase;EC=3.6.3.49 cAMP-dependent chloride channel; 
Organism
Rattus norvegicus (Rat) 
NCBI Taxonomy ID
10116 
Chromosome Location
chr:4;43874852-44041870;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Temporarily unavailable 
The information of related literatures
1. W. M. Xu, J. Chen, H. Chen, R. Y. Diao, K. L. Fok, J. D. Dong, T. T. Sun, W. Y. Chen, M. K. Yu, X. H. Zhang, L. L. Tsang, A. Lau, Q. X. Shi, Q. H. Shi, P. B. Huang and H. C. Chan (2011) Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia. PLoS One 6(5): e19120. 

Abstract
Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO(3) (-) transport and the expression of the HCO(3) (-) sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO(3) (-) could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases. PMID: [21625623] 

2. A. E. Trezise and M. Buchwald (1991) In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator. Nature 353(6343): 434-7. 

Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The principal manifestations of CF include increased concentration of Cl- in exocrine gland secretions, pancreatic insufficiency, chronic lung disease, intestinal blockage and malabsorption of fat, and male and female infertility. Insight into the function of CFTR can be gained by correlating its cell-specific expression with the physiology of those cells and with CF pathology. Determination of CFTR messenger RNA in rat tissues by in situ hybridization shows that it is specifically expressed in the ductal cells of the pancreas and the salivary glands. In the intestine, decreasing gradients of expression of the CFTR gene are observed on both the crypt-villus and the proximal-distal axes. This expression is consistent with CFTR being responsible for bidirectional Cl- transport, secretion in the intestinal crypts and reabsorption in the silivary gland ducts, and suggests that in these tissues CFTR functions as a regulated Cl- channel. In the lung, a broad band of hybridization includes the mucosa and submucosa of the bronchi and bronchioles. In the testis, CFTR expression is regulated during the cycle of the seminiferous epithelium. Postmeiotic expression is maximal in the round spermatids of stages VII and VIII, suggesting that CFTR plays a critical role in spermatogenesis and that deficiency of this function contributes to CF male infertility. PMID: [1716739] 

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Figures for illustrating the function of this protein/gene
Ref: W. M. Xu, J. Chen, H. Chen, R. Y. Diao, K. L. Fok, J. D. Dong, T. T. Sun, W. Y. Chen, M. K. Yu, X. H. Zhang, L. L. Tsang, A. Lau, Q. X. Shi, Q. H. Shi, P. B. Huang and H. C. Chan (2011) Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia. PLoS One 6(5): e19120. PMID: [21625623]
Ref: W. M. Xu, J. Chen, H. Chen, R. Y. Diao, K. L. Fok, J. D. Dong, T. T. Sun, W. Y. Chen, M. K. Yu, X. H. Zhang, L. L. Tsang, A. Lau, Q. X. Shi, Q. H. Shi, P. B. Huang and H. C. Chan (2011) Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia. PLoS One 6(5): e19120. PMID: [21625623]
Function
Involved in the transport of chloride ions. May regulatebicarbonate secretion and salvage in epithelial cells byregulating the SLC4A7 transporter. 
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Subcellular Location
Membrane; Multi-pass membrane protein. 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0016324 C:apical plasma membrane IDA:RGD.
GO:0016323 C:basolateral plasma membrane IDA:RGD.
GO:0034707 C:chloride channel complex IEA:UniProtKB-KW.
GO:0030659 C:cytoplasmic vesicle membrane IDA:RGD.
GO:0005769 C:early endosome ISS:UniProtKB.
GO:0005902 C:microvillus IDA:RGD.
GO:0005524 F:ATP binding IEA:UniProtKB-KW.
GO:0005260 F:channel-conductance-controlling ATPase activity IEA:EC.
GO:0006200 P:ATP catabolic process IEA:GOC.
GO:0015701 P:bicarbonate transport IMP:RGD.
GO:0007589 P:body fluid secretion TAS:RGD.
GO:0032870 P:cellular response to hormone stimulus IEP:RGD.
GO:0006695 P:cholesterol biosynthetic process IEA:Compara.
GO:0030301 P:cholesterol transport IEA:Compara.
GO:0015705 P:iodide transport IMP:RGD.
GO:0030324 P:lung development IMP:RGD.
GO:0045909 P:positive regulation of vasodilation IDA:RGD.
GO:0034097 P:response to cytokine stimulus IEP:RGD.
GO:0042493 P:response to drug IEP:RGD.
GO:0043627 P:response to estrogen stimulus IEP:RGD.
GO:0043434 P:response to peptide hormone stimulus IEP:RGD.
GO:0030321 P:transepithelial chloride transport IMP:RGD.
GO:0042311 P:vasodilation IMP:RGD.
GO:0006833 P:water transport IMP:RGD.
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Interpro
IPR003593;    AAA+_ATPase.
IPR003439;    ABC_transporter-like.
IPR017871;    ABC_transporter_CS.
IPR017940;    ABC_transporter_type1.
IPR001140;    ABC_transptr_TM_dom.
IPR011527;    ABC_transptrTM_dom_typ1.
IPR005291;    cAMP_cl_channel.
IPR025837;    CFTR_reg_dom.
IPR009147;    CysFib_conduc_TM.
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Pfam
PF00664;    ABC_membrane;    2.
PF00005;    ABC_tran;    2.
PF14396;    CFTR_R;    1.
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SMART
SM00382;    AAA;    2.
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PROSITE
PS50929;    ABC_TM1F;    2.
PS00211;    ABC_TRANSPORTER_1;    1.
PS50893;    ABC_TRANSPORTER_2;    2.
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PRINTS
PR01851;    CYSFIBREGLTR.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1   1476       Cystic fibrosis transmembrane conductance
                             regulator.
                             /FTId=PRO_0000093428.
TOPO_DOM      1     80       Cytoplasmic (Potential).
TRANSMEM     81    103       Helical; Name=1; (Potential).
TOPO_DOM    104    117       Extracellular (Potential).
TRANSMEM    118    138       Helical; Name=2; (Potential).
TOPO_DOM    139    194       Cytoplasmic (Potential).
TRANSMEM    195    215       Helical; Name=3; (Potential).
TOPO_DOM    216    220       Extracellular (Potential).
TRANSMEM    221    241       Helical; Name=4; (Potential).
TOPO_DOM    242    307       Cytoplasmic (Potential).
TRANSMEM    308    328       Helical; Name=5; (Potential).
TOPO_DOM    329    330       Extracellular (Potential).
TRANSMEM    331    350       Helical; Name=6; (Potential).
TOPO_DOM    351    854       Cytoplasmic (Potential).
TRANSMEM    855    875       Helical; Name=7; (Potential).
TOPO_DOM    876    906       Extracellular (Potential).
TRANSMEM    907    927       Helical; Name=8; (Potential).
TOPO_DOM    928    985       Cytoplasmic (Potential).
TRANSMEM    986   1006       Helical; Name=9; (Potential).
TOPO_DOM   1007   1008       Extracellular (Potential).
TRANSMEM   1009   1029       Helical; Name=10; (Potential).
TOPO_DOM   1030   1097       Cytoplasmic (Potential).
TRANSMEM   1098   1118       Helical; Name=11; (Potential).
TOPO_DOM   1119   1123       Extracellular (Potential).
TRANSMEM   1124   1144       Helical; Name=12; (Potential).
TOPO_DOM   1145   1476       Cytoplasmic (Potential).
DOMAIN       81    365       ABC transmembrane type-1 1.
DOMAIN      412    646       ABC transporter 1.
DOMAIN      854   1153       ABC transmembrane type-1 2.
DOMAIN     1208   1439       ABC transporter 2.
NP_BIND     458    465       ATP (Potential).
NP_BIND    1240   1247       ATP (Potential).
MOTIF      1474   1476       PDZ-binding (By similarity).
MOD_RES     515    515       Phosphotyrosine (By similarity).
MOD_RES     660    660       Phosphoserine (By similarity).
MOD_RES     684    684       Phosphoserine (By similarity).
MOD_RES     698    698       Phosphoserine (By similarity).
MOD_RES     710    710       Phosphoserine (By similarity).
MOD_RES     715    715       Phosphothreonine (By similarity).
MOD_RES     732    732       Phosphoserine (By similarity).
MOD_RES     763    763       Phosphoserine (By similarity).
MOD_RES     785    785       Phosphoserine (By similarity).
MOD_RES     790    790       Phosphoserine (By similarity).
MOD_RES     808    808       Phosphoserine (By similarity).
MOD_RES    1172   1172       Phosphothreonine (By similarity).
MOD_RES    1440   1440       Phosphoserine (By similarity).
MOD_RES    1452   1452       Phosphoserine (By similarity).
LIPID       524    524       S-palmitoyl cysteine (By similarity).
LIPID      1391   1391       S-palmitoyl cysteine (By similarity).
CARBOHYD    889    889       N-linked (GlcNAc...) (Potential).
CARBOHYD    895    895       N-linked (GlcNAc...) (Potential).
CONFLICT    987    988       FD -> LT (in Ref. 3; AAA40918).
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Nucleotide Sequence
Length: bp   Go to nucleotide: FASTA
Protein Sequence
Length: 1476 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
Slc4a7BioGRID 
Other Protein-Protein interaction resources
String database  
View Microarray data
Temporarily unavailable 
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