Protein:TBX3 |
Protein Summary |
 Gene summary |
| Gene name: TBX3 | ASpdb.0 ID: 6926 | Gene | Gene symbol | TBX3 | Gene ID | 6926 |
| Gene name | T-box transcription factor 3 |
| Synonyms | TBX3-ISO|UMS|XHL |
| Cytomap | 12q24.21 |
| Type of gene | protein-coding |
| Description | T-box transcription factor TBX3T-box 3T-box protein 3bladder cancer related protein XHL |
| Modification date | 20240305 |
| UniProtAcc | O15119 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TBX3 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 11689487 |
| Gene | TBX3 | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | 11689487|12000749|22130515 |
| Gene | TBX3 | GO:0001227 | DNA-binding transcription repressor activity, RNA polymerase II-specific | 11689487|22130515 |
| Gene | TBX3 | GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | 22130515 |
| Gene | TBX3 | GO:0005634 | nucleus | 11689487 |
| Gene | TBX3 | GO:0008284 | positive regulation of cell population proliferation | 12032820 |
| Gene | TBX3 | GO:0009887 | animal organ morphogenesis | 9207801 |
| Gene | TBX3 | GO:0035136 | forelimb morphogenesis | 9207801 |
| Gene | TBX3 | GO:0043066 | negative regulation of apoptotic process | 12032820 |
| Gene | TBX3 | GO:0043565 | sequence-specific DNA binding | 11689487 |
| Gene | TBX3 | GO:0045662 | negative regulation of myoblast differentiation | 12032820 |
| Gene | TBX3 | GO:0045787 | positive regulation of cell cycle | 12032820 |
| Gene | TBX3 | GO:0045892 | negative regulation of DNA-templated transcription | 10468588|11689487 |
| Gene | TBX3 | GO:0060931 | sinoatrial node cell development | 22130515 |
| Gene | TBX3 | GO:0090398 | cellular senescence | 11748239|22002537 |
| Gene | TBX3 | GO:1990837 | sequence-specific double-stranded DNA binding | 28473536 |
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 |
| O15119-1 | O15119-1_1h6f_B.pdb | 1H6F | X-ray | 1.7 | B | 101 | 305 |
| 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 |
| O15119 | TBX3 | O15119-1 | O15119-2 | 743 | 723 | 221 | 240 | Deletion | none | none | 220 | 220 |
| O15119 | TBX3 | O15119-1 | O15119-3 | 743 | 600 | 490 | 615 | Deletion | none | none | 489 | 489 |
| O15119 | TBX3 | O15119-1 | O15119-3 | 743 | 600 | 661 | 677 | Deletion | none | none | 534 | 534 |
| Multiple sequence alignment of our canonical and alternatively spliced TBX3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TBX3 |
| UniProt-id | ENSG | ENST | ENSP |
| O15119-1 | ENSG00000135111.16 | ENST00000257566.7 | ENSP00000257566.3 |
| O15119-2 | ENSG00000135111.16 | ENST00000349155.7 | ENSP00000257567.2 |
| UniProt-id | NM ID | NP ID |
| O15119-1 | NM_016569.3 | NP_057653.3 |
| O15119-2 | NM_005996.3 | NP_005987.3 |
| Amino acid sequences of our canonical and alternatively spliced TBX3 |
| accession_id | Protein sequence |
| O15119-1 | MSLSMRDPVIPGTSMAYHPFLPHRAPDFAMSAVLGHQPPFFPALTLPPNGAAALSLPGALAKPIMDQLVGAAETGIPFSSLGPQAHLRPL KTMEPEEEVEDDPKVHLEAKELWDQFHKRGTEMVITKSGRRMFPPFKVRCSGLDKKAKYILLMDIIAADDCRYKFHNSRWMVAGKADPEM PKRMYIHPDSPATGEQWMSKVVTFHKLKLTNNISDKHGFTLAFPSDHATWQGNYSFGTQTILNSMHKYQPRFHIVRANDILKLPYSTFRT YLFPETEFIAVTAYQNDKITQLKIDNNPFAKGFRDTGNGRREKRKQLTLQSMRVFDERHKKENGTSDESSSEQAAFNCFAQASSPAASTV GTSNLKDLCPSEGESDAEAESKEEHGPEACDAAKISTTTSEEPCRDKGSPAVKAHLFAAERPRDSGRLDKASPDSRHSPATISSSTRGLG AEERRSPVREGTAPAKVEEARALPGKEAFAPLTVQTDAAAAHLAQGPLPGLGFAPGLAGQQFFNGHPLFLHPSQFAMGGAFSSMAAAGMG PLLATVSGASTGVSGLDSTAMASAAAAQGLSGASAATLPFHLQQHVLASQGLAMSPFGSLFPYPYTYMAAAAAASSAAASSSVHRHPFLN LNTMRPRLRYSPYSIPVPVPDGSSLLTTALPSMAAAAGPLDGKVAALAASPASVAVDSGSELNSRSSTLSSSSMSLSPKLCAEKEAATSE |
| O15119-2 | MSLSMRDPVIPGTSMAYHPFLPHRAPDFAMSAVLGHQPPFFPALTLPPNGAAALSLPGALAKPIMDQLVGAAETGIPFSSLGPQAHLRPL KTMEPEEEVEDDPKVHLEAKELWDQFHKRGTEMVITKSGRRMFPPFKVRCSGLDKKAKYILLMDIIAADDCRYKFHNSRWMVAGKADPEM PKRMYIHPDSPATGEQWMSKVVTFHKLKLTNNISDKHGFTILNSMHKYQPRFHIVRANDILKLPYSTFRTYLFPETEFIAVTAYQNDKIT QLKIDNNPFAKGFRDTGNGRREKRKQLTLQSMRVFDERHKKENGTSDESSSEQAAFNCFAQASSPAASTVGTSNLKDLCPSEGESDAEAE SKEEHGPEACDAAKISTTTSEEPCRDKGSPAVKAHLFAAERPRDSGRLDKASPDSRHSPATISSSTRGLGAEERRSPVREGTAPAKVEEA RALPGKEAFAPLTVQTDAAAAHLAQGPLPGLGFAPGLAGQQFFNGHPLFLHPSQFAMGGAFSSMAAAGMGPLLATVSGASTGVSGLDSTA MASAAAAQGLSGASAATLPFHLQQHVLASQGLAMSPFGSLFPYPYTYMAAAAAASSAAASSSVHRHPFLNLNTMRPRLRYSPYSIPVPVP DGSSLLTTALPSMAAAAGPLDGKVAALAASPASVAVDSGSELNSRSSTLSSSSMSLSPKLCAEKEAATSELQSIQRLVSGLEAKPDRSRS |
| O15119-3 | MSLSMRDPVIPGTSMAYHPFLPHRAPDFAMSAVLGHQPPFFPALTLPPNGAAALSLPGALAKPIMDQLVGAAETGIPFSSLGPQAHLRPL KTMEPEEEVEDDPKVHLEAKELWDQFHKRGTEMVITKSGRRMFPPFKVRCSGLDKKAKYILLMDIIAADDCRYKFHNSRWMVAGKADPEM PKRMYIHPDSPATGEQWMSKVVTFHKLKLTNNISDKHGFTLAFPSDHATWQGNYSFGTQTILNSMHKYQPRFHIVRANDILKLPYSTFRT YLFPETEFIAVTAYQNDKITQLKIDNNPFAKGFRDTGNGRREKRKQLTLQSMRVFDERHKKENGTSDESSSEQAAFNCFAQASSPAASTV GTSNLKDLCPSEGESDAEAESKEEHGPEACDAAKISTTTSEEPCRDKGSPAVKAHLFAAERPRDSGRLDKASPDSRHSPATISSSTRGLG AEERRSPVREGTAPAKVEEARALPGKEAFAPLTVQTDAASAAASSSVHRHPFLNLNTMRPRLRYSPYSIPVPVPDGSSLLTTALAASPAS |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TBX3 (go to UniProt):O15119 |
| 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 |
| O15119 | Region | 544 | 695 | Note=Transcription repression | Type=Deletion;Start=490;End=615 |
| O15119 | Region | 544 | 695 | Note=Transcription repression | Type=Deletion;Start=661;End=677 |
Gene Isoform Structures and Expression Levels for TBX3 |
| Gene structures of our canonical and alternative spliced genes of TBX3 * 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 O15119-1 |
| 3D view using mol* of O15119-2 |
| 3D view using mol* of O15119-3 |
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 O15119-1 |
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| pLDDT distribution across the protein length of O15119-2 |
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| pLDDT distribution across the protein length of O15119-3 |
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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 O15119-1 |
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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 |
| O15119-1 | 1.027 | 122 | 1.05 | 389.305 | 0.566 | 0.725 | 0.982 | 0.616 | 0.997 | 0.618 | 0.786 | 17,154,181,182,183,184,219,220,221,222,223,224,229 ,230,231,233,234,236,237,251,253,261,263,264,267,2 68,270 |
| O15119-2 | 1.006 | 101 | 1.02 | 249.361 | 0.524 | 0.708 | 0.991 | 0.753 | 1.056 | 0.713 | 0.524 | 107,108,109,112,113,123,124,130,131,132,133,134,13 5,136,137,205,207,208,209,264,270,273,274,277,278, 279,280 |
| O15119-3 | 1.024 | 166 | 1.062 | 529.592 | 0.587 | 0.695 | 0.934 | 0.769 | 0.906 | 0.848 | 1.31 | 15,17,154,182,183,184,218,219,220,221,222,223,224, 229,230,231,232,233,234,235,236,237,251,253,263,26 4,268,270 |
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 O15119-1_O15119-1_1h6f_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O15119-1_1h6f_B_O15119-2.pdb |
| 3D view using mol* of O15119-1_1h6f_B_O15119-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O15119-1_O15119-2.pdb |
| 3D view using mol* of O15119-1_O15119-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O15119-1_vs_O15119-2.png |
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| ./stats/secondary_structure/figure/O15119-1_vs_O15119-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O15119-1_vs_O15119-2.png |
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| ./stats/relative_asa/O15119-1_vs_O15119-3.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 TBX3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to TBX3 |
| Previous studies relating to the alternative splicing of TBX3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TBX3 | 15289316 | TBX3 and its isoform TBX3+2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast cancer cell lines. | TBX3 is a transcription factor of the T-box gene family. Mutations of TBX3 cause ulnar-mammary syndrome (MIM 181450) in humans, an autosomal dominant disorder characterized by the absence or underdevelopment of the mammary glands and other congenital anomalies. It recently was found that TBX3 was able to immortalize mouse embryo fibroblast (MEF) cells. In addition, TBX2, a homologue of TBX3, is active in preventing senescence in rodent cells and was found to be amplified in some human breast cancers, suggesting TBX3 plays a role in breast cancer. This study examined the function of TBX3 and its isoform, TBX3 + 2a. TBX3 + 2a differs from TBX3 in the DNA binding domain with an extra 20 amino acids produced by alternative splicing. We first examined the tissue expression and alternative splicing patterns of these two isoforms. We found that TBX3 and TBX3 + 2a are widely expressed in humans and mice, and alternative splicing could be tissue specific and species specific. Overexpression of TBX3 is able to immortalize MEF cells, whereas TBX3 + 2a shows an acceleration of senescence, a functional difference that may be explained by the fact that these two isoforms may have different downstream targets. TBX3, but not TBX3 + 2a, is able to bind to the previously identified T-box binding site in a gel shift assay. A subset of human breast cancer cell lines overexpresses TBX3. Our results indicate that TBX3 and TBX3 + 2a are functionally distinctive in inhibition of senescence of MEF cells and may play a role in breast cancer. | D001943 | Breast Neoplasms |
| TBX3 | 24675841 | TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome. | TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing. | D000015 | Abnormalities, Multiple |
| TBX3 | 24675841 | TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome. | TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing. | D001941 | Breast Diseases |
| TBX3 | 24675841 | TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome. | TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing. | D009421 | Nervous System Malformations |
Clinically important variants in TBX3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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