Protein:FGFR3 |
Protein Summary |
 Gene summary |
| Gene name: FGFR3 | ASpdb.0 ID: 2261 | Gene | Gene symbol | FGFR3 | Gene ID | 2261 |
| Gene name | fibroblast growth factor receptor 3 |
| Synonyms | ACH|CD333|CEK2|HSFGFR3EX|JTK4 |
| Cytomap | 4p16.3 |
| Type of gene | protein-coding |
| Description | fibroblast growth factor receptor 3FGFR-3fibroblast growth factor receptor 3-Shydroxyaryl-protein kinasetyrosine kinase JTK4 |
| Modification date | 20240413 |
| UniProtAcc | P22607 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | FGFR3 | GO:0004713 | protein tyrosine kinase activity | 11294897 |
| Gene | FGFR3 | GO:0005783 | endoplasmic reticulum | - |
| Gene | FGFR3 | GO:0005794 | Golgi apparatus | 18061161 |
| Gene | FGFR3 | GO:0005886 | plasma membrane | 8663044|18061161 |
| Gene | FGFR3 | GO:0008543 | fibroblast growth factor receptor signaling pathway | 8663044 |
| Gene | FGFR3 | GO:0017134 | fibroblast growth factor binding | 8663044 |
| Gene | FGFR3 | GO:0030133 | transport vesicle | 18061161 |
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 |
| P22607-1 | P22607-1_6pnx_A.pdb | 6PNX | X-ray | 2.2 | A | 456 | 757 |
| 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 |
| P22607 | FGFR3 | P22607-1 | P22607-2 | 806 | 808 | 311 | 358 | Substitution | TAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLP | SWISESVEADVRLRLANVSERDGGEYLCRATNFIGVAEKAFWLSVHGPRA | 311 | 360 |
| P22607 | FGFR3 | P22607-1 | P22607-3 | 806 | 694 | 311 | 422 | Deletion | none | none | 310 | 310 |
| P22607 | FGFR3 | P22607-1 | P22607-4 | 806 | 791 | 654 | 806 | Substitution | GRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT | LVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPGPCPYRDVHRRVPGPVGAFRAVLPGWPGHPQLQLLRGRLRVCPRPAAPGPTQQWGLADVKGHWSPTM | 654 | 791 |
| Multiple sequence alignment of our canonical and alternatively spliced FGFR3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of FGFR3 |
| UniProt-id | ENSG | ENST | ENSP |
| P22607-1 | ENSG00000068078.20 | ENST00000440486.8 | ENSP00000414914.2 |
| P22607-2 | ENSG00000068078.20 | ENST00000340107.9 | ENSP00000339824.4 |
| P22607-3 | ENSG00000068078.20 | ENST00000352904.6 | ENSP00000231803.1 |
| UniProt-id | NM ID | NP ID |
| P22607-1 | NM_000142.4 | NP_000133.1 |
| P22607-2 | NM_001163213.1 | NP_001156685.1 |
| P22607-3 | NM_022965.3 | NP_075254.1 |
| Amino acid sequences of our canonical and alternatively spliced FGFR3 |
| accession_id | Protein sequence |
| P22607-1 | MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVG PQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSD VEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAE EELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGPT LANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIIN LLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNV MKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCT |
| P22607-2 | MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVG PQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSD VEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKSWISESVEADVRLRLANVSERDGGEYLCRATNFIGVAEKAFWLSVHGPRA AEEELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEG PTLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNI INLLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTED NVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPAN |
| P22607-3 | MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVG PQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSD VEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARL TLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAKGN LREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTT NGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFK |
| P22607-4 | MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVG PQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSD VEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAE EELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGPT LANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIIN LLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNV MKIADFGLARDVHNLDYYKKTTNLVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAA |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| FGFR3 (go to UniProt):P22607 |
| 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 |
| P22607 | Topological domain | 23 | 375 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=311;End=358 |
| P22607 | Topological domain | 23 | 375 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=311;End=422 |
| P22607 | Transmembrane | 376 | 396 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=311;End=422 |
| P22607 | Topological domain | 397 | 806 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=311;End=422 |
| P22607 | Topological domain | 397 | 806 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=654;End=806 |
| P22607 | Domain | 253 | 355 | Note=Ig-like C2-type 3 | Type=Substitution;Start=311;End=358 |
| P22607 | Domain | 253 | 355 | Note=Ig-like C2-type 3 | Type=Deletion;Start=311;End=422 |
| P22607 | Domain | 472 | 761 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Substitution;Start=654;End=806 |
| P22607 | Region | 765 | 806 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=654;End=806 |
| P22607 | Compositional bias | 770 | 787 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=654;End=806 |
Gene Isoform Structures and Expression Levels for FGFR3 |
| Gene structures of our canonical and alternative spliced genes of FGFR3 * 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. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
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 P22607-1 |
| 3D view using mol* of P22607-2 |
| 3D view using mol* of P22607-3 |
| 3D view using mol* of P22607-4 |
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 P22607-1 |
 |
| pLDDT distribution across the protein length of P22607-2 |
 |
| pLDDT distribution across the protein length of P22607-3 |
 |
| pLDDT distribution across the protein length of P22607-4 |
 |
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 P22607-1 |
 |
| Ramachandran plot of P22607-2 |
 |
| Ramachandran plot of P22607-3 |
 |
| Ramachandran plot of P22607-4 |
 |
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 |
| P22607-1 | 1.042 | 222 | 1.056 | 667.478 | 0.503 | 0.761 | 0.986 | 0.87 | 1.047 | 0.832 | 0.614 | 476,477,478,479,480,481,482,483,486,506,508,517,51 8,521,522,525,529,539,553,555,556,557,558,561,562, 616,617,621,622,624,634,635,636,637,638,640,648,65 0,651,652,654,655,656,657,671 |
| P22607-2 | 1.061 | 655 | 1.099 | 2072.406 | 0.499 | 0.743 | 0.941 | 0.866 | 0.88 | 0.984 | 0.698 | 167,168,169,200,201,202,203,216,217,219,220,247,24 8,249,250,280,281,343,344,438,439,440,442,444,457, 459,461,478,480,481,482,483,484,485,486,487,488,50 8,510,511,512,518,519,520,521,522,523,524,525,526, 527,529,530,531,533,534,541,557,558,559,560,561,56 3,564,613,614,615,618,619,623,624,626,636,637,638, 639,640,642,643,646,647,648,649,650,651,652,653,65 4,655,656,657,658,659,660,661,662,663,667,671,672, 673,695,696,698,699,700,701,702,703 |
| P22607-3 | 1.044 | 400 | 1.053 | 1281.448 | 0.486 | 0.764 | 0.999 | 0.735 | 1.058 | 0.695 | 0.619 | 169,248,249,251,252,253,284,369,370,371,372,373,37 4,396,397,398,405,406,409,410,412,413,415,416,419, 420,499,500,501,504,505,523,525,526,528,529,532,53 3,534,535,536,537,538,539,540,541,542,543,544,545, 549,553,554,555,556,557,558,559,560 |
| P22607-4 | 1.068 | 214 | 1.121 | 642.096 | 0.58 | 0.723 | 0.9 | 1.125 | 0.776 | 1.45 | 0.977 | 478,479,480,481,482,483,484,485,486,506,508,509,51 0,518,521,522,524,525,527,528,529,531,532,539,553, 555,556,557,558,561,562,611,612,613,616,621,622,62 4,634,635,636,637,638,639,640,641,642,644,645 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P22607-1_P22607-1_6pnx_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P22607-1_6pnx_A_P22607-2.pdb |
| 3D view using mol* of P22607-1_6pnx_A_P22607-3.pdb |
| 3D view using mol* of P22607-1_6pnx_A_P22607-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P22607-1_P22607-2.pdb |
| 3D view using mol* of P22607-1_P22607-3.pdb |
| 3D view using mol* of P22607-1_P22607-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P22607-1_vs_P22607-2.png |
 < |
| ./stats/secondary_structure/figure/P22607-1_vs_P22607-3.png |
 < |
| ./stats/secondary_structure/figure/P22607-1_vs_P22607-4.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P22607-1_vs_P22607-2.png |
 < |
| ./stats/relative_asa/P22607-1_vs_P22607-3.png |
 < |
| ./stats/relative_asa/P22607-1_vs_P22607-4.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to FGFR3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P22607 | FGFR3 | DB09078 | Lenvatinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB09079 | Nintedanib | approved | inhibitor |
| P22607 | FGFR3 | DB05014 | XL999 | investigational | |
| P22607 | FGFR3 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB08901 | Ponatinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB15685 | Selpercatinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB15102 | Pemigatinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB12147 | Erdafitinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB11886 | Infigratinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB06589 | Pazopanib | approved | inhibitor |
| P22607 | FGFR3 | DB15149 | Futibatinib | approved, investigational | inhibitor |
| P22607 | FGFR3 | DB17587 | KIN-3248 | investigational | inhibitor |
Related Diseases to FGFR3 |
| Previous studies relating to the alternative splicing of FGFR3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| FGFR3 | 7495869 | The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific. | An essential feature of fibroblast growth factor receptors (FGFR) is the existence of multiple possibilities for alternative splicing. One of these concerns sequences of the mRNA coding for the C-terminal half of Ig domain 3 which corresponds to a part of the ligand-binding site. Two alternative exons, IIIb and IIIc, encode the C-terminal half of Ig domain 3. We show here that the alternative splicing choice between IIIb and IIIc exons of the FGFR-3 is not strictly tissue-specific: epithelial cells show exclusively IIIb transcripts while fibroblastic cells show a mixture of IIIb and IIIc transcripts. This is in contrast with the strictly exclusive alternative choice between IIIb or IIIc exons of the FGFR-2 gene: epithelial cells make only the IIIb choice while fibroblastic cells make only the IIIc choice. | D003110 | Colonic Neoplasms |
| FGFR3 | 7495869 | The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific. | An essential feature of fibroblast growth factor receptors (FGFR) is the existence of multiple possibilities for alternative splicing. One of these concerns sequences of the mRNA coding for the C-terminal half of Ig domain 3 which corresponds to a part of the ligand-binding site. Two alternative exons, IIIb and IIIc, encode the C-terminal half of Ig domain 3. We show here that the alternative splicing choice between IIIb and IIIc exons of the FGFR-3 is not strictly tissue-specific: epithelial cells show exclusively IIIb transcripts while fibroblastic cells show a mixture of IIIb and IIIc transcripts. This is in contrast with the strictly exclusive alternative choice between IIIb or IIIc exons of the FGFR-2 gene: epithelial cells make only the IIIb choice while fibroblastic cells make only the IIIc choice. | D008545 | Melanoma |
| FGFR3 | 7495869 | The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific. | An essential feature of fibroblast growth factor receptors (FGFR) is the existence of multiple possibilities for alternative splicing. One of these concerns sequences of the mRNA coding for the C-terminal half of Ig domain 3 which corresponds to a part of the ligand-binding site. Two alternative exons, IIIb and IIIc, encode the C-terminal half of Ig domain 3. We show here that the alternative splicing choice between IIIb and IIIc exons of the FGFR-3 is not strictly tissue-specific: epithelial cells show exclusively IIIb transcripts while fibroblastic cells show a mixture of IIIb and IIIc transcripts. This is in contrast with the strictly exclusive alternative choice between IIIb or IIIc exons of the FGFR-2 gene: epithelial cells make only the IIIb choice while fibroblastic cells make only the IIIc choice. | D001749 | Urinary Bladder Neoplasms |
| FGFR3 | 12368157 | Novel mutation and RNA splice variant of fibroblast growth factor receptor 3 in multiple myeloma patients at diagnosis. | The karyotypically silent t(4;14)(p16.3;q32) translocation can be found in approximately 15-20% of multiple myeloma (MM) patients and results in the ectopic expression of fibroblast growth factor receptor 3 (FGFR3) from der4. Point mutations in specific FGFR3 domains can be found in the translocated allele, and have been recently proven to be oncogenic. These mutations produce a constitutively activated receptor, which shows dimerization and autophosphorylation even in the absence of ligand. We investigated the presence of FGFR3 expression and activating mutations in a series of newly diagnosed MM patients. | D009101 | Multiple Myeloma |
| FGFR3 | 14520460 | FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells. | Fibroblast growth factor receptor 3 (FGFR3) is one of four high-affinity tyrosine kinase receptors for the FGF family of ligands, frequently associated with growth arrest and induction of differentiation. The extracellular immunoglobulin (IgG)-like domains II and III are responsible for ligand binding; alternative usage of exons IIIb and IIIc of the Ig-like domain III determining the ligand-binding specificity of the receptor. By reverse transcriptase polymerase chain reaction (RT-PCR) a novel FGFR3IIIc variant FGFR3IIIS, expressed in a high proportion of tumours and tumour cell lines but rarely in normal tissues, has been identified. Unlike recently described nonsense transcripts of FGFR3, the coding region of FGFR3IIIS remains in-frame producing a novel protein. The protein product is coexpressed with FGFR3IIIc in the membrane and soluble cell fractions; expression in the soluble fraction is decreased after exposure to bFGF but not aFGF. Knockout of FGFR3IIIS using antisense has a growth-inhibitory effect in vitro, suggesting a dominant-negative function for FGFR3IIIS inhibiting FGFR3-induced growth arrest. In summary, alternative splicing of the FGFR3 Ig-domain III represents a mechanism for the generation of receptor diversity. FGFR3IIIS may regulate FGF and FGFR trafficking and function, possibly contributing to the development of a malignant phenotype. | D009369 | Neoplasms |
| FGFR3 | 16288035 | Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines. | Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that play key roles in proliferation, differentiation, and tumorigenesis. FGFR3 was identified as the major family member expressed in both normal human urothelium and cultured normal human urothelial (NHU) cells and was expressed as the IIIb isoform. We also identified a splice variant, FGFR3 Delta8-10, lacking exons encoding the COOH-terminal half of immunoglobulin-like domain III and the transmembrane domain. Previous reports have assumed that this is a cancer-specific splice variant. We showed that FGFR3 Delta8-10 is a normal transcript in NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium expressed high levels of FGFR3 transcripts. In culture, levels were reduced in actively proliferating cells but increased at confluence and as cells approached senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Delta8-10. In bladder tumor cell lines derived from aggressive carcinomas, there were significant alterations in the relative expression of isoforms including an overall decrease in the proportion of FGFR3 Delta8-10 and predominant expression of FGFR3 IIIc in some cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a normal mechanism to generate a transcript that regulates proliferation and in bladder cancer, the ratio of FGFR3 isoforms is significantly altered. | D002292 | Carcinoma, Renal Cell |
| FGFR3 | 16288035 | Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines. | Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that play key roles in proliferation, differentiation, and tumorigenesis. FGFR3 was identified as the major family member expressed in both normal human urothelium and cultured normal human urothelial (NHU) cells and was expressed as the IIIb isoform. We also identified a splice variant, FGFR3 Delta8-10, lacking exons encoding the COOH-terminal half of immunoglobulin-like domain III and the transmembrane domain. Previous reports have assumed that this is a cancer-specific splice variant. We showed that FGFR3 Delta8-10 is a normal transcript in NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium expressed high levels of FGFR3 transcripts. In culture, levels were reduced in actively proliferating cells but increased at confluence and as cells approached senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Delta8-10. In bladder tumor cell lines derived from aggressive carcinomas, there were significant alterations in the relative expression of isoforms including an overall decrease in the proportion of FGFR3 Delta8-10 and predominant expression of FGFR3 IIIc in some cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a normal mechanism to generate a transcript that regulates proliferation and in bladder cancer, the ratio of FGFR3 isoforms is significantly altered. | D007680 | Kidney Neoplasms |
| FGFR3 | 16288035 | Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines. | Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that play key roles in proliferation, differentiation, and tumorigenesis. FGFR3 was identified as the major family member expressed in both normal human urothelium and cultured normal human urothelial (NHU) cells and was expressed as the IIIb isoform. We also identified a splice variant, FGFR3 Delta8-10, lacking exons encoding the COOH-terminal half of immunoglobulin-like domain III and the transmembrane domain. Previous reports have assumed that this is a cancer-specific splice variant. We showed that FGFR3 Delta8-10 is a normal transcript in NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium expressed high levels of FGFR3 transcripts. In culture, levels were reduced in actively proliferating cells but increased at confluence and as cells approached senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Delta8-10. In bladder tumor cell lines derived from aggressive carcinomas, there were significant alterations in the relative expression of isoforms including an overall decrease in the proportion of FGFR3 Delta8-10 and predominant expression of FGFR3 IIIc in some cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a normal mechanism to generate a transcript that regulates proliferation and in bladder cancer, the ratio of FGFR3 isoforms is significantly altered. | D001749 | Urinary Bladder Neoplasms |
| FGFR3 | 16288035 | Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines. | Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that play key roles in proliferation, differentiation, and tumorigenesis. FGFR3 was identified as the major family member expressed in both normal human urothelium and cultured normal human urothelial (NHU) cells and was expressed as the IIIb isoform. We also identified a splice variant, FGFR3 Delta8-10, lacking exons encoding the COOH-terminal half of immunoglobulin-like domain III and the transmembrane domain. Previous reports have assumed that this is a cancer-specific splice variant. We showed that FGFR3 Delta8-10 is a normal transcript in NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium expressed high levels of FGFR3 transcripts. In culture, levels were reduced in actively proliferating cells but increased at confluence and as cells approached senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Delta8-10. In bladder tumor cell lines derived from aggressive carcinomas, there were significant alterations in the relative expression of isoforms including an overall decrease in the proportion of FGFR3 Delta8-10 and predominant expression of FGFR3 IIIc in some cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a normal mechanism to generate a transcript that regulates proliferation and in bladder cancer, the ratio of FGFR3 isoforms is significantly altered. | D014571 | Urologic Neoplasms |
Clinically important variants in FGFR3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |