Protein:FGFR4 |
Protein Summary |
 Gene summary |
| Gene name: FGFR4 | ASpdb.0 ID: 2264 | Gene | Gene symbol | FGFR4 | Gene ID | 2264 |
| Gene name | fibroblast growth factor receptor 4 |
| Synonyms | CD334|JTK2|TKF |
| Cytomap | 5q35.2 |
| Type of gene | protein-coding |
| Description | fibroblast growth factor receptor 4hydroxyaryl-protein kinaseprotein-tyrosine kinasetyrosine kinase related to fibroblast growth factor receptortyrosylprotein kinase |
| Modification date | 20240411 |
| UniProtAcc | P22455 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | FGFR4 | GO:0005007 | fibroblast growth factor receptor activity | 8663044|18480409|21653700 |
| Gene | FGFR4 | GO:0005783 | endoplasmic reticulum | 20683963 |
| Gene | FGFR4 | GO:0005794 | Golgi apparatus | 18061161 |
| Gene | FGFR4 | GO:0005886 | plasma membrane | 18061161|20683963 |
| Gene | FGFR4 | GO:0005911 | cell-cell junction | 20798051 |
| Gene | FGFR4 | GO:0008201 | heparin binding | 18480409 |
| Gene | FGFR4 | GO:0008284 | positive regulation of cell population proliferation | 8663044 |
| Gene | FGFR4 | GO:0008543 | fibroblast growth factor receptor signaling pathway | 21653700 |
| Gene | FGFR4 | GO:0017134 | fibroblast growth factor binding | 8663044|18480409 |
| Gene | FGFR4 | GO:0018108 | peptidyl-tyrosine phosphorylation | 18480409|20683963 |
| Gene | FGFR4 | GO:0030133 | transport vesicle | 18061161 |
| Gene | FGFR4 | GO:0046777 | protein autophosphorylation | 20798051 |
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 |
| P22455-1 | P22455-1_4tyj_A.pdb | 4TYJ | X-ray | 2.45 | A | 447 | 753 |
| 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 |
| P22455 | FGFR4 | P22455-1 | P22455-2 | 802 | 762 | 353 | 416 | Substitution | EEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLAR | GTGRIPHLTCDSLTPAGRTKSPTL | 353 | 376 |
| P22455 | FGFR4 | P22455-1 | P22455-3 | 802 | 592 | 1 | 210 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced FGFR4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of FGFR4 |
| UniProt-id | ENSG | ENST | ENSP |
| P22455-1 | ENSG00000160867.15 | ENST00000292408.9 | ENSP00000292408.4 |
| P22455-1 | ENSG00000160867.15 | ENST00000502906.5 | ENSP00000424960.1 |
| P22455-2 | ENSG00000160867.15 | ENST00000393637.5 | ENSP00000377254.1 |
| UniProt-id | NM ID | NP ID |
| P22455-1 | NM_002011.4 | NP_002002.3 |
| P22455-1 | NM_213647.2 | NP_998812.1 |
| P22455-2 | NM_022963.3 | NP_075252.2 |
| Amino acid sequences of our canonical and alternatively spliced FGFR4 |
| accession_id | Protein sequence |
| P22455-1 | MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIAS FLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTP TIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELL CKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTA AAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLV SLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVC TQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIAD FGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYG |
| P22455-2 | MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIAS FLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTP TIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELL CKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPGTGRIPHL TCDSLTPAGRTKSPTLQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMD PARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSS EGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQS DVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLT |
| P22455-3 | MESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFP YVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLY RGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQ VVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGP DLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEA LFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAV |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| FGFR4 (go to UniProt):P22455 |
| 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 |
| P22455 | Topological domain | 22 | 369 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=353;End=416 |
| P22455 | Topological domain | 22 | 369 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=210 |
| P22455 | Transmembrane | 370 | 390 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=353;End=416 |
| P22455 | Topological domain | 391 | 802 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=353;End=416 |
| P22455 | Domain | 22 | 118 | Note=Ig-like C2-type 1 | Type=Deletion;Start=1;End=210 |
| P22455 | Domain | 152 | 240 | Note=Ig-like C2-type 2 | Type=Deletion;Start=1;End=210 |
| P22455 | Region | 119 | 148 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=210 |
| P22455 | Compositional bias | 124 | 138 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=210 |
Gene Isoform Structures and Expression Levels for FGFR4 |
| Gene structures of our canonical and alternative spliced genes of FGFR4 * 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 P22455-1 |
| 3D view using mol* of P22455-2 |
| 3D view using mol* of P22455-3 |
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 P22455-1 |
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| pLDDT distribution across the protein length of P22455-2 |
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| pLDDT distribution across the protein length of P22455-3 |
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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 P22455-1 |
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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 |
| P22455-1 | 1.044 | 148 | 1.1 | 529.249 | 0.677 | 0.687 | 0.866 | 0.734 | 0.773 | 0.949 | 1.573 | 563,564,565,566,567,568,569,570,572,573,576,577,57 8,579,581,582,583,584,585,586,589,680,683,684,685, 712,713,759,761,762,763,764 |
| P22455-2 | 1.096 | 217 | 1.128 | 598.878 | 0.483 | 0.798 | 1.023 | 1.086 | 0.892 | 1.218 | 0.975 | 433,434,436,437,438,439,440,441,461,463,465,473,47 6,477,480,484,494,508,510,511,512,513,516,517,519, 520,523,576,577,579,589,590,591,592,593,596,597,59 8,599,600,602,603,610 |
| P22455-3 | 1.043 | 285 | 1.058 | 856.128 | 0.528 | 0.76 | 0.982 | 0.954 | 1.036 | 0.92 | 0.561 | 263,264,266,267,268,269,270,271,273,291,293,295,30 2,303,306,307,309,310,313,314,316,317,324,338,340, 341,342,343,344,346,347,396,397,398,402,406,407,40 9,419,420,421,422,423,424,425,426,427,428,429,433, 435,437,439,440,442 |
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 P22455-1_P22455-1_4tyj_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 P22455-1_4tyj_A_P22455-2.pdb |
| 3D view using mol* of P22455-1_4tyj_A_P22455-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P22455-1_P22455-2.pdb |
| 3D view using mol* of P22455-1_P22455-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P22455-1_vs_P22455-2.png |
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| ./stats/secondary_structure/figure/P22455-1_vs_P22455-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P22455-1_vs_P22455-2.png |
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| ./stats/relative_asa/P22455-1_vs_P22455-3.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 FGFR4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P22455 | FGFR4 | DB01109 | Heparin | approved, investigational | |
| P22455 | FGFR4 | DB12147 | Erdafitinib | approved, investigational | inhibitor |
| P22455 | FGFR4 | DB09078 | Lenvatinib | approved, investigational | inhibitor |
| P22455 | FGFR4 | DB15102 | Pemigatinib | approved, investigational | inhibitor |
| P22455 | FGFR4 | DB08901 | Ponatinib | approved, investigational | inhibitor |
| P22455 | FGFR4 | DB15149 | Futibatinib | approved, investigational | inhibitor |
| P22455 | FGFR4 | DB11886 | Infigratinib | approved, investigational | inhibitor |
Related Diseases to FGFR4 |
| Previous studies relating to the alternative splicing of FGFR4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| FGFR4 | 11549253 | A soluble dominant negative fibroblast growth factor receptor 4 isoform in human MCF-7 breast cancer cells. | Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases encoded by four closely related genes. FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor with three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain, and a split intracellular kinase. Here we describe a novel C-terminally truncated soluble isoform of FGFR4 expressed by human epithelial breast cancer MCF-7 cells. This isoform results from failure of splicing of intron 4 resulting in an mRNA species that encodes an in-frame premature stop codon. Cells transfected with the corresponding cDNA containing intron 4 express a truncated releasable protein that is identified in conditioned media. This soluble FGFR4 isoform (sFGFR4) abrogates the effect of FGF-1-induced MAPK phosphorylation and PRL gene activation. These findings represent the first description of an endogenous soluble C-terminally truncated FGFR4 isoform with FGF modulatory properties. | D001943 | Breast Neoplasms |
| FGFR4 | 18593464 | Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. | Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF)--a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins--many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis. | D001172 | Arthritis, Rheumatoid |
| FGFR4 | 18593464 | Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. | Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF)--a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins--many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis. | D004195 | Disease Models, Animal |
Clinically important variants in FGFR4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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