Protein:FSHR |
Protein Summary |
 Gene summary |
| Gene name: FSHR | ASpdb.0 ID: 2492 | Gene | Gene symbol | FSHR | Gene ID | 2492 |
| Gene name | follicle stimulating hormone receptor |
| Synonyms | FSHR1|FSHRO|LGR1|ODG1 |
| Cytomap | 2p16.3 |
| Type of gene | protein-coding |
| Description | follicle-stimulating hormone receptorFSH receptorfollitropin receptor |
| Modification date | 20240403 |
| UniProtAcc | P23945 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | FSHR | GO:0004963 | follicle-stimulating hormone receptor activity | 24692546 |
| Gene | FSHR | GO:0005886 | plasma membrane | 11847099 |
| Gene | FSHR | GO:0007186 | G protein-coupled receptor signaling pathway | 24692546 |
| Gene | FSHR | GO:0016020 | membrane | 24692546 |
| Gene | FSHR | GO:0042699 | follicle-stimulating hormone signaling pathway | 24692546 |
| Gene | FSHR | GO:0043235 | receptor complex | 24692546 |
| Gene | FSHR | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 24058690 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P23945-1 | P23945-1_4ay9_X.pdb | 4AY9 | X-ray | 2.5 | X | 18 | 359 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P23945 | FSHR | P23945-1 | P23945-2 | 695 | 633 | 224 | 285 | Deletion | none | none | 223 | 223 |
| P23945 | FSHR | P23945-1 | P23945-3 | 695 | 669 | 149 | 174 | Deletion | none | none | 148 | 148 |
| P23945 | FSHR | P23945-1 | P23945-4 | 695 | 729 | 223 | 223 | Substitution | L | LNRRTRTPTEPNVLLAKYPSGQGVLEEPESLSSSI | 223 | 257 |
| Multiple sequence alignment of our canonical and alternatively spliced FSHR |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of FSHR |
| UniProt-id | ENSG | ENST | ENSP |
| UniProt-id | NM ID | NP ID |
| Amino acid sequences of our canonical and alternatively spliced FSHR |
| accession_id | Protein sequence |
| P23945-1 | MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRVIQKGAFSGFGDLEKIEISQNDVLEVIEADV FSNLPKLHEIRIEKANNLLYINPEAFQNLPNLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILDISRTRIHSLPSYGLENLKKLRARSTYNLKKLPTLEKLVALMEASLT YPSHCCAFANWRRQISELHPICNKSILRQEVDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIM GYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIASVDIHTKSQYHNYAIDWQTGAGCDAAGFFTV FASELSVYTLTAITLERWHTITHAMQLDCKVQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVL AFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVPLITVSKAKILLVLFHPINSCANPFLYAIFT |
| P23945-2 | MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRVIQKGAFSGFGDLEKIEISQNDVLEVIEADV FSNLPKLHEIRIEKANNLLYINPEAFQNLPNLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILSELHPICNKSILRQEVDYMTQARGQRSSLAEDNESSYSRGFDMTYTE FDYDLCNEVVDVTCSPKPDAFNPCEDIMGYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIASVD IHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCKVQLRHAASVMVMGWIFAFAAALFPIFGISSYM KVSICLPMDIDSPLSQLYVMSLLVLNVLAFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVPLI TVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSSTVHNTHPRNGHCSSAPRVTNGSTYILVPLSHL |
| P23945-3 | MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRVIQKGAFSGFGDLEKIEISQNDVLEVIEADV FSNLPKLHEIRIEKANNLLYINPEAFQNLPNLQYLLISNTGIKHLPDVHKIHSLQKVLLWLNKNGIQEIHNCAFNGTQLDELNLSDNNNL EELPNDVFHGASGPVILDISRTRIHSLPSYGLENLKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSI LRQEVDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIMGYNILRVLIWFISILAITGNIIVLVI LTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIASVDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQ LDCKVQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVLAFVVICGCYIHIYLTVRNPNIVSSSS DTRIAKRMAMLIFTDFLCMAPISFFAISASLKVPLITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRT |
| P23945-4 | MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRVIQKGAFSGFGDLEKIEISQNDVLEVIEADV FSNLPKLHEIRIEKANNLLYINPEAFQNLPNLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILNRRTRTPTEPNVLLAKYPSGQGVLEEPESLSSSIDISRTRIHSLPSY GLENLKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSILRQEVDYMTQARGQRSSLAEDNESSYSRGF DMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIMGYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLL LIASVDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCKVQLRHAASVMVMGWIFAFAAALFPIF GISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVLAFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISAS LKVPLITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSSTVHNTHPRNGHCSSAPRVTNGSTYIL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| FSHR (go to UniProt):P23945 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P23945 | Topological domain | 18 | 366 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=224;End=285 |
| P23945 | Topological domain | 18 | 366 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=149;End=174 |
| P23945 | Topological domain | 18 | 366 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=223;End=223 |
| P23945 | Repeat | 144 | 169 | Note=LRR 5 | Type=Deletion;Start=149;End=174 |
| P23945 | Repeat | 170 | 192 | Note=LRR 6 | Type=Deletion;Start=149;End=174 |
| P23945 | Repeat | 217 | 240 | Note=LRR 8 | Type=Deletion;Start=224;End=285 |
| P23945 | Repeat | 217 | 240 | Note=LRR 8 | Type=Substitution;Start=223;End=223 |
| P23945 | Repeat | 241 | 259 | Note=LRR 9 | Type=Deletion;Start=224;End=285 |
Gene Isoform Structures and Expression Levels for FSHR |
| Gene structures of our canonical and alternative spliced genes of FSHR * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P23945-1 |
| 3D view using mol* of P23945-2 |
| 3D view using mol* of P23945-3 |
| 3D view using mol* of P23945-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P23945-1 |
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| pLDDT distribution across the protein length of P23945-2 |
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| pLDDT distribution across the protein length of P23945-3 |
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| pLDDT distribution across the protein length of P23945-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P23945-1 |
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| Ramachandran plot of P23945-2 |
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| Ramachandran plot of P23945-3 |
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| Ramachandran plot of P23945-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P23945-1 | 1.23 | 186 | 1.318 | 349.86 | 0.35 | 0.87 | 1.097 | 3.097 | 0.441 | 7.023 | 2.298 | 352,353,449,450,453,454,514,516,518,519,520,522,53 1,534,535,538,585,588,589,591,592,595,596,598,600, 602,603,604,607,610,611,615 |
| P23945-2 | 1.259 | 188 | 1.347 | 357.749 | 0.326 | 0.907 | 1.156 | 3.111 | 0.421 | 7.388 | 3.462 | 290,291,387,388,391,392,452,454,456,457,458,460,46 9,472,473,476,523,526,529,530,533,534,536,538,540, 541,542,545,548,549,553 |
| P23945-3 | 1.094 | 293 | 1.152 | 669.879 | 0.568 | 0.746 | 0.901 | 1.58 | 0.722 | 2.188 | 1.99 | 221,222,224,242,243,244,245,246,247,321,322,325,32 7,328,329,388,403,407,408,411,412,413,414,417,423, 424,427,428,478,479,481,484,485,486,487,488,489,49 0,492,493,494,495,496,497,498,504,505,508,509,512, 559,562,563,565,566,568,569,570,572,574,575,576,57 7,578,581,582,584,585,589 |
| P23945-4 | 1.153 | 254 | 1.212 | 527.191 | 0.427 | 0.822 | 1.039 | 2.037 | 0.678 | 3.004 | 1.736 | 305,306,307,385,386,387,388,448,463,467,468,471,47 2,483,484,487,488,546,547,548,550,552,553,554,555, 556,557,565,568,569,572,619,622,623,625,626,628,62 9,630,632,634,635,636,637,638,641,644,645,649 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P23945-1_P23945-1_4ay9_X.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P23945-1_4ay9_X_P23945-2.pdb |
| 3D view using mol* of P23945-1_4ay9_X_P23945-3.pdb |
| 3D view using mol* of P23945-1_4ay9_X_P23945-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P23945-1_P23945-2.pdb |
| 3D view using mol* of P23945-1_P23945-3.pdb |
| 3D view using mol* of P23945-1_P23945-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P23945-1_vs_P23945-2.png |
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| ./stats/secondary_structure/figure/P23945-1_vs_P23945-3.png |
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| ./stats/secondary_structure/figure/P23945-1_vs_P23945-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P23945-1_vs_P23945-2.png |
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| ./stats/relative_asa/P23945-1_vs_P23945-3.png |
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| ./stats/relative_asa/P23945-1_vs_P23945-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to FSHR |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P23945 | FSHR | DB09066 | Corifollitropin alfa | approved, investigational | agonist |
| P23945 | FSHR | DB00097 | Choriogonadotropin alfa | approved | binder |
| P23945 | FSHR | DB00066 | Follitropin | approved | agonist |
| P23945 | FSHR | DB00094 | Urofollitropin | approved, vet_approved | agonist |
| P23945 | FSHR | DB00032 | Menotropins | approved | binder |
| P23945 | FSHR | DB04786 | Suramin | investigational | antagonist |
Related Diseases to FSHR |
| Previous studies relating to the alternative splicing of FSHR and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| FSHR | 24670307 | Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH. | Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function. | D007247 | Infertility, Female |
Clinically important variants in FSHR |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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