SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000611 
UniProt Accession
Theoretical PI
6.76  
Molecular Weight
78265 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
FSHR 
Gene Synonyms/Alias
LGR1 
Protein Name
Follicle-stimulating hormone receptor 
Protein Synonyms/Alias
FSH-R Follitropin receptor;Flags: Precursor 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:2;49189296-49381676;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
These results question the essential role of FSH for the initiation of spermatogenesis, and demonstrate that FSH is more important for female than for male fertility. 
The information of related literatures
1. T. Ishikawa, M. Fujisawa and J. Tapanainen (2006) Screening of FSH receptor gene mutation (C566T) in azoospermic men in Japan. Arch Androl 52(1): 15-9. 

Abstract
To study the genetic mutation, which could cause problems in spermatogenesis, we screened the point mutations of the FSH receptor gene (C566T) in idiopathic azoospermic men in Japan. We performed mutational analysis of the FSH receptor in 54 Japanese patients diagnosed for azoospermia with Sertoli cell-only (SCO) syndrome (n = 33), hypospermatogenesis (n = 11) and maturation arrest (n = 10). For mutation screening of the FSH receptor, polymerase chain reaction (PCR) amplification from genomic DNA with flanking intronic primers were used. On BsmI digestion, all patients demonstrated homozygous, normal exon 7 alleles with 51 and 27 bp fragments. The absence of any 78 bp fragments demonstrated that no heterozygous or homozygous mutant alleles were present in any patients. None of the 54 patients showed a C566T FSH receptor mutation. We could not confirm that the genomic mutation of the FSH receptor (C566T) is a common cause in Japanese azoospermic patients. PMID: [16338864] 

2. J. S. Tapanainen, K. Aittomaki, J. Min, T. Vaskivuo and I. T. Huhtaniemi (1997) Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat Genet 15(2): 205-6. 

Abstract
Gonadal function is controlled by the two pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). While LH mainly regulates gonadal steroidogenesis, FSH is considered essential for folliculogenesis in the female and spermatogenesis in the male. We recently discovered that an inactivating point mutation in the FSH receptor (R) gene causes a recessively inherited form of hypergonadotropic ovarian failure in homozygous females. This 566C-->T mutation, predicting an alanine to valine substitution, is located in exon 7 of the FSHR gene, in the region encoding the extracellular domain of the receptor molecule. Functional testing showed a clear-cut reduction in ligand binding and signal transduction by the mutated receptor. Hence, lack of FSH function is incompatible with ovarian follicular maturation and female fertility. In the male, FSH is generally considered essential for the pubertal initiation of spermatogenesis and maintenance of quantitatively normal sperm production in adults. We report here the first characterization of males homozygous for an inactivating FSHR mutation. They have variable degrees of spermatogenic failure, but, surprisingly, do not show azoospermia or absolute infertility. These results question the essential role of FSH for the initiation of spermatogenesis, and demonstrate that FSH is more important for female than for male fertility. PMID: [9020851] 

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Figures for illustrating the function of this protein/gene
Function
Receptor for follicle-stimulating hormone. The activityof this receptor is mediated by G proteins which activateadenylate cyclase. 
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Subcellular Location
Cell membrane; Multi-pass membrane protein. 
Tissue Specificity
Sertoli cells and ovarian granulosa cells. 
Gene Ontology
GO IDGO termEvidence
GO:0009986 C:cell surface IEA:Compara.
GO:0005768 C:endosome IEA:Compara.
GO:0016021 C:integral to membrane TAS:ProtInc.
GO:0005886 C:plasma membrane TAS:Reactome.
GO:0004963 F:follicle-stimulating hormone receptor activity TAS:ProtInc.
GO:0017046 F:peptide hormone binding IEA:Compara.
GO:0007189 P:adenylate cyclase-activating G-protein coupled receptor signaling pathway IEA:Compara.
GO:0007292 P:female gamete generation TAS:ProtInc.
GO:0008584 P:male gonad development IEP:UniProtKB.
GO:0033044 P:regulation of chromosome organization IEA:Compara.
GO:0007283 P:spermatogenesis TAS:ProtInc.
GO:0035093 P:spermatogenesis, exchange of chromosomal proteins IEA:Compara.
GO:0045056 P:transcytosis IEA:Compara.
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Interpro
IPR000276;    7TM_GPCR_Rhodpsn.
IPR002272;    FSH_rcpt.
IPR024635;    GnHR_TM.
IPR017452;    GPCR_Rhodpsn_supfam.
IPR002131;    Gphrmn_rcpt.
IPR000372;    LRR-contain_N.
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Pfam
PF00001;    7tm_1;    1.
PF12369;    GnHR_trans;    1.
PF01462;    LRRNT;    1.
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SMART
SM00013;    LRRNT;    1.
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PROSITE
PS00237;    G_PROTEIN_RECEP_F1_1;    1.
PS50262;    G_PROTEIN_RECEP_F1_2;    1.
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PRINTS
PR01143;    FSHRECEPTOR.;   
PR00373;    GLYCHORMONER.;   
PR00237;    GPCRRHODOPSN.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
SIGNAL        1     17       Potential.
CHAIN        18    695       Follicle-stimulating hormone receptor.
                             /FTId=PRO_0000012771.
TOPO_DOM     18    366       Extracellular (Potential).
TRANSMEM    367    387       Helical; Name=1; (Potential).
TOPO_DOM    388    398       Cytoplasmic (Potential).
TRANSMEM    399    421       Helical; Name=2; (Potential).
TOPO_DOM    422    443       Extracellular (Potential).
TRANSMEM    444    465       Helical; Name=3; (Potential).
TOPO_DOM    466    485       Cytoplasmic (Potential).
TRANSMEM    486    508       Helical; Name=4; (Potential).
TOPO_DOM    509    528       Extracellular (Potential).
TRANSMEM    529    550       Helical; Name=5; (Potential).
TOPO_DOM    551    573       Cytoplasmic (Potential).
TRANSMEM    574    597       Helical; Name=6; (Potential).
TOPO_DOM    598    608       Extracellular (Potential).
TRANSMEM    609    630       Helical; Name=7; (Potential).
TOPO_DOM    631    695       Cytoplasmic (Potential).
DOMAIN       18     46       LRRNT.
REPEAT       49     72       LRR 1.
REPEAT       73     97       LRR 2.
REPEAT       98    118       LRR 3.
REPEAT      119    143       LRR 4.
REPEAT      144    169       LRR 5.
REPEAT      170    192       LRR 6.
REPEAT      193    216       LRR 7.
REPEAT      217    240       LRR 8.
REPEAT      241    259       LRR 9.
CARBOHYD    191    191       N-linked (GlcNAc...).
CARBOHYD    199    199       N-linked (GlcNAc...) (Potential).
CARBOHYD    293    293       N-linked (GlcNAc...) (By similarity).
CARBOHYD    318    318       N-linked (GlcNAc...) (Potential).
DISULFID     18     25
DISULFID     23     32
DISULFID    442    517       By similarity.
VAR_SEQ     149    174       Missing (in isoform 3).
                             /FTId=VSP_043181.
VAR_SEQ     224    285       Missing (in isoform Short).
                             /FTId=VSP_001953.
VARIANT     128    128       S -> Y (in OHSS; displays increase in
                             affinity and sensitivity toward hCG and
                             does not show any constitutive activity
                             nor promiscuous activation by TSH).
                             /FTId=VAR_039279.
VARIANT     160    160       I -> T (in ODG1; impairs cell surface
                             expression).
                             /FTId=VAR_018045.
VARIANT     189    189       A -> V (in ODG1; very frequent in the
                             Finnish population).
                             /FTId=VAR_018046.
VARIANT     224    224       D -> V (in ODG1; FSH binding is barely
                             detectable; impaired targeting to the
                             cell membrane; adenylate cyclase
                             stimulation by FSH is 4 +-2% residual
                             activity).
                             /FTId=VAR_039280.
VARIANT     307    307       A -> T (in dbSNP:rs6165).
                             /FTId=VAR_013903.
VARIANT     348    348       P -> R (in ODG1).
                             /FTId=VAR_039281.
VARIANT     419    419       A -> T (in ODG1).
                             /FTId=VAR_018047.
VARIANT     449    449       T -> A (in OHSS; increase of receptor
                             sensitivity to both hCG and TSH together
                             with an increase in basal activity).
                             /FTId=VAR_039282.
VARIANT     449    449       T -> I (in OHSS; dbSNP:rs28928870).
                             /FTId=VAR_017244.
VARIANT     519    519       P -> T (in ODG1; totally impairs
                             adenylate cyclase stimulation in vitro;
                             alters the cell surface targeting of the
                             receptor which remains trapped
                             intracellularly).
                             /FTId=VAR_039283.
VARIANT     524    524       S -> R (in dbSNP:rs6167).
                             /FTId=VAR_013904.
VARIANT     545    545       I -> T (in OHSS; displays promiscuous
                             activation by both hCG and TSH together
                             with detectable constitutive activity).
                             /FTId=VAR_039284.
VARIANT     567    567       D -> G (in FSHR activation; 1.5-fold
                             increase in basal cAMP production
                             compared to the wild-type receptor
                             indicating that this mutation leads to
                             ligand-independent constitutive
                             activation).
                             /FTId=VAR_039285.
VARIANT     567    567       D -> N (in OHSS; dbSNP:rs28928871).
                             /FTId=VAR_017245.
VARIANT     573    573       R -> C (in ODG1; alters signal
                             transduction of the receptor; adenylate
                             cyclase stimulation by FSH is 24 +-4%
                             residual activity).
                             /FTId=VAR_018048.
VARIANT     591    591       F -> S (in ovarian sex cord tumor; loss
                             of function).
                             /FTId=VAR_018049.
VARIANT     601    601       L -> V (in ODG1; binds FSH with a similar
                             affinity than the wild-type receptor;
                             adenylate cyclase stimulation by FSH is
                             12 +-3% residual activity).
                             /FTId=VAR_039286.
VARIANT     680    680       N -> S (associated with longer menstrual
                             cycles; dbSNP:rs6166).
                             /FTId=VAR_013905.
CONFLICT     13     13       S -> R (in Ref. 8; CAA48179).
CONFLICT    112    112       N -> T (in Ref. 1; AAA52477).
CONFLICT    197    198       EL -> AV (in Ref. 1; AAA52477).
CONFLICT    295    295       S -> P (in Ref. 8; CAA48179).
STRAND       21     25
STRAND       27     34
STRAND       49     55
TURN         63     68
STRAND       74     79
STRAND       88     93
STRAND       99    103
STRAND      115    117
STRAND      124    129
STRAND      143    145
STRAND      147    153
STRAND      168    171
STRAND      173    176
TURN        187    192
STRAND      195    199
TURN        211    216
STRAND      221    224
STRAND      235    237
STRAND      243    253
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Nucleotide Sequence
Length: 2393 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 695 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
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