Protein:TGFBR2 |
Protein Summary |
 Gene summary |
| Gene name: TGFBR2 | ASpdb.0 ID: 7048 | Gene | Gene symbol | TGFBR2 | Gene ID | 7048 |
| Gene name | transforming growth factor beta receptor 2 |
| Synonyms | AAT3|FAA3|LDS1B|LDS2|LDS2B|MFS2|RIIC|TAAD2|TBR-ii|TBRII|TGFR-2|TGFbeta-RII|tbetaR-II |
| Cytomap | 3p24.1 |
| Type of gene | protein-coding |
| Description | TGF-beta receptor type-2TGF-beta receptor type IIBTGF-beta type II receptortransforming growth factor beta receptor IItransforming growth factor beta receptor type IICtransforming growth factor, beta receptor II (70/80kDa)transforming growth factor, |
| Modification date | 20240416 |
| UniProtAcc | P37173 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TGFBR2 | GO:0004675 | transmembrane receptor protein serine/threonine kinase activity | 12015308 |
| Gene | TGFBR2 | GO:0005024 | transforming growth factor beta receptor activity | 7852346|12015308|18453574 |
| Gene | TGFBR2 | GO:0005539 | glycosaminoglycan binding | 7852346 |
| Gene | TGFBR2 | GO:0005886 | plasma membrane | 25893292 |
| Gene | TGFBR2 | GO:0005901 | caveola | 17878231 |
| Gene | TGFBR2 | GO:0006915 | apoptotic process | 17471240 |
| Gene | TGFBR2 | GO:0007179 | transforming growth factor beta receptor signaling pathway | 1333888|9311995|12015308|18453574 |
| Gene | TGFBR2 | GO:0009410 | response to xenobiotic stimulus | 17878231 |
| Gene | TGFBR2 | GO:0009897 | external side of plasma membrane | 18453574 |
| Gene | TGFBR2 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 26459119 |
| Gene | TGFBR2 | GO:0016020 | membrane | 7852346 |
| Gene | TGFBR2 | GO:0043235 | receptor complex | 7852346|8774881 |
| Gene | TGFBR2 | GO:0045121 | membrane raft | 25893292 |
| Gene | TGFBR2 | GO:0046332 | SMAD binding | 11157754|18453574 |
| Gene | TGFBR2 | GO:0050431 | transforming growth factor beta binding | 7852346|18243111|18453574 |
| Gene | TGFBR2 | GO:0060391 | positive regulation of SMAD protein signal transduction | 18453574 |
| Gene | TGFBR2 | GO:0070723 | response to cholesterol | 17878231 |
| Gene | TGFBR2 | GO:2000563 | positive regulation of CD4-positive, alpha-beta T cell proliferation | 17164348 |
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 |
| P37173-1 | P37173-1_5e92_A.pdb | 5E92 | X-ray | 2.08 | A | 240 | 543 |
| 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 |
| P37173 | TGFBR2 | P37173-1 | P37173-2 | 567 | 592 | 31 | 32 | Substitution | SV | SDVEMEAQKDEIICPSCNRTAHPLRHI | 31 | 57 |
| Multiple sequence alignment of our canonical and alternatively spliced TGFBR2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TGFBR2 |
| UniProt-id | ENSG | ENST | ENSP |
| P37173-1 | ENSG00000163513.19 | ENST00000295754.10 | ENSP00000295754.5 |
| P37173-2 | ENSG00000163513.19 | ENST00000359013.4 | ENSP00000351905.4 |
| UniProt-id | NM ID | NP ID |
| P37173-1 | NM_003242.5 | NP_003233.4 |
| P37173-2 | NM_001024847.2 | NP_001020018.1 |
| Amino acid sequences of our canonical and alternatively spliced TGFBR2 |
| accession_id | Protein sequence |
| P37173-1 | MGRGLLRGLWPLHIVLWTRIASTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRK NDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDLLLVIFQVTGISLLPPLGVAI SVIIIFYCYRVNRQQKLSSTWETGKTRKLMEFSEHCAIILEDDRSDISSTCANNINHNTELLPIELDTLVGKGRFAEVYKAKLKQNTSEQ FETVAVKIFPYEEYASWKTEKDIFSDINLKHENILQFLTAEERKTELGKQYWLITAFHAKGNLQEYLTRHVISWEDLRKLGSSLARGIAH LHSDHTPCGRPKMPIVHRDLKSSNILVKNDLTCCLCDFGLSLRLDPTLSVDDLANSGQVGTARYMAPEVLESRMNLENVESFKQTDVYSM ALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDNVLRDRGRPEIPSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSE |
| P37173-2 | MGRGLLRGLWPLHIVLWTRIASTIPPHVQKSDVEMEAQKDEIICPSCNRTAHPLRHINNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQK SCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNT SNPDLLLVIFQVTGISLLPPLGVAISVIIIFYCYRVNRQQKLSSTWETGKTRKLMEFSEHCAIILEDDRSDISSTCANNINHNTELLPIE LDTLVGKGRFAEVYKAKLKQNTSEQFETVAVKIFPYEEYASWKTEKDIFSDINLKHENILQFLTAEERKTELGKQYWLITAFHAKGNLQE YLTRHVISWEDLRKLGSSLARGIAHLHSDHTPCGRPKMPIVHRDLKSSNILVKNDLTCCLCDFGLSLRLDPTLSVDDLANSGQVGTARYM APEVLESRMNLENVESFKQTDVYSMALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDNVLRDRGRPEIPSFWLNHQGIQMVCE |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TGFBR2 (go to UniProt):P37173 |
| 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 |
| P37173 | Topological domain | 23 | 166 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=31;End=32 |
Gene Isoform Structures and Expression Levels for TGFBR2 |
| Gene structures of our canonical and alternative spliced genes of TGFBR2 * 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 P37173-1 |
| 3D view using mol* of P37173-2 |
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 P37173-1 |
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| pLDDT distribution across the protein length of P37173-2 |
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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 P37173-1 |
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| Ramachandran plot of P37173-2 |
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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 |
| P37173-1 | 1.039 | 234 | 1.008 | 507.64 | 0.46 | 0.756 | 1.006 | 0.728 | 1.183 | 0.615 | 0.728 | 250,251,252,253,254,255,256,258,275,276,277,290,29 4,305,323,325,326,327,328,329,330,331,332,334,335, 336,339,379,381,383,384,386,396,397,398,399,400,42 0,421,422,423,424,472,480,481,482 |
| P37173-2 | 1.041 | 235 | 0.997 | 477.113 | 0.44 | 0.759 | 0.978 | 0.8 | 1.22 | 0.655 | 0.724 | 275,276,277,278,279,280,281,283,300,302,315,319,33 0,348,350,352,353,354,356,357,359,360,404,406,407, 408,409,411,421,422,423,424,425,445,446,447,448,44 9,497,505,506,507 |
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 P37173-1_P37173-1_5e92_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 P37173-1_5e92_A_P37173-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P37173-1_P37173-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P37173-1_vs_P37173-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P37173-1_vs_P37173-2.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 TGFBR2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P37173 | TGFBR2 | DB10772 | Foreskin keratinocyte (neonatal) | approved | agonist |
| P37173 | TGFBR2 | DB10770 | Foreskin fibroblast (neonatal) | approved | agonist |
| P37173 | TGFBR2 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
Related Diseases to TGFBR2 |
| Previous studies relating to the alternative splicing of TGFBR2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TGFBR2 | 24846200 | The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma. | Alternative splicing is an important mechanism that can disrupt cell cycle control resulting in tumorigenesis. Although many alterations of Transforming Growth Factor Beta (TGFβ) signaling are reported in cancers, the role of splice aberrations in destabilizing this signaling is the least understood mechanism. In this study, we compared TGFBR2 alternative splicing events in potentially malignant oral disorders (PMDs) and oral squamous cell carcinoma (OSCC) samples with those in normal samples. Interestingly, there were five alternatively spliced forms of TGFBR2 with a deficient kinase domain in OSCCs. The TGFBR2 aberrant splicing was tumor-specific, suggesting that selective splicing out of TGFBR2 kinase domain could be a mechanism misused by cancer cells for evading TGFβ signaling-mediated anti-tumor activities. Moreover, these aberrant transcripts were present in PMDs as well, suggesting an early occurrence of these events during oral carcinogenesis and offering the possibility of early diagnosis of malignancy. Furthermore, OSCC patients who harbored these aberrantly spliced transcripts exhibited poor disease free survival (p=0.028) and poor overall survival (p=0.013). Thus, assessing the presence of these TGFBR2 transcripts can serve as a prognostic marker for oral cancer. | D063646 | Carcinogenesis |
| TGFBR2 | 24846200 | The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma. | Alternative splicing is an important mechanism that can disrupt cell cycle control resulting in tumorigenesis. Although many alterations of Transforming Growth Factor Beta (TGFβ) signaling are reported in cancers, the role of splice aberrations in destabilizing this signaling is the least understood mechanism. In this study, we compared TGFBR2 alternative splicing events in potentially malignant oral disorders (PMDs) and oral squamous cell carcinoma (OSCC) samples with those in normal samples. Interestingly, there were five alternatively spliced forms of TGFBR2 with a deficient kinase domain in OSCCs. The TGFBR2 aberrant splicing was tumor-specific, suggesting that selective splicing out of TGFBR2 kinase domain could be a mechanism misused by cancer cells for evading TGFβ signaling-mediated anti-tumor activities. Moreover, these aberrant transcripts were present in PMDs as well, suggesting an early occurrence of these events during oral carcinogenesis and offering the possibility of early diagnosis of malignancy. Furthermore, OSCC patients who harbored these aberrantly spliced transcripts exhibited poor disease free survival (p=0.028) and poor overall survival (p=0.013). Thus, assessing the presence of these TGFBR2 transcripts can serve as a prognostic marker for oral cancer. | D002294 | Carcinoma, Squamous Cell |
| TGFBR2 | 24846200 | The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma. | Alternative splicing is an important mechanism that can disrupt cell cycle control resulting in tumorigenesis. Although many alterations of Transforming Growth Factor Beta (TGFβ) signaling are reported in cancers, the role of splice aberrations in destabilizing this signaling is the least understood mechanism. In this study, we compared TGFBR2 alternative splicing events in potentially malignant oral disorders (PMDs) and oral squamous cell carcinoma (OSCC) samples with those in normal samples. Interestingly, there were five alternatively spliced forms of TGFBR2 with a deficient kinase domain in OSCCs. The TGFBR2 aberrant splicing was tumor-specific, suggesting that selective splicing out of TGFBR2 kinase domain could be a mechanism misused by cancer cells for evading TGFβ signaling-mediated anti-tumor activities. Moreover, these aberrant transcripts were present in PMDs as well, suggesting an early occurrence of these events during oral carcinogenesis and offering the possibility of early diagnosis of malignancy. Furthermore, OSCC patients who harbored these aberrantly spliced transcripts exhibited poor disease free survival (p=0.028) and poor overall survival (p=0.013). Thus, assessing the presence of these TGFBR2 transcripts can serve as a prognostic marker for oral cancer. | D009062 | Mouth Neoplasms |
Clinically important variants in TGFBR2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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