Protein:TUBB3 |
Protein Summary |
 Gene summary |
| Gene name: TUBB3 | ASpdb.0 ID: 10381 | Gene | Gene symbol | TUBB3 | Gene ID | 10381 |
| Gene name | tubulin beta 3 class III |
| Synonyms | CDCBM|CDCBM1|CFEOM3|CFEOM3A|FEOM3|TUBB4|beta-4 |
| Cytomap | 16q24.3 |
| Type of gene | protein-coding |
| Description | tubulin beta-3 chainclass III beta-tubulintubulin beta-4 chaintubulin beta-IIItubulin, beta 3 |
| Modification date | 20240407 |
| UniProtAcc | Q13509 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TUBB3 | GO:0000226 | microtubule cytoskeleton organization | 34996871 |
| Gene | TUBB3 | GO:0005200 | structural constituent of cytoskeleton | 34996871 |
| Gene | TUBB3 | GO:0005525 | GTP binding | 34996871 |
| Gene | TUBB3 | GO:0005874 | microtubule | 21525035 |
| Gene | TUBB3 | GO:0015630 | microtubule cytoskeleton | 34996871 |
| Gene | TUBB3 | GO:0015630 | microtubule cytoskeleton | - |
| Gene | TUBB3 | GO:0045171 | intercellular bridge | - |
| Gene | TUBB3 | GO:0072686 | mitotic spindle | - |
| Gene | TUBB3 | GO:1990791 | dorsal root ganglion development | 28483977 |
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 |
| Q13509-1 | Q13509-1_6wsl_B.pdb | 6WSL | EM | 3.1 | B | 1 | 429 |
| 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 |
| Q13509 | TUBB3 | Q13509-1 | Q13509-2 | 450 | 378 | 1 | 72 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced TUBB3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TUBB3 |
| UniProt-id | ENSG | ENST | ENSP |
| Q13509-1 | ENSG00000258947.8 | ENST00000315491.12 | ENSP00000320295.7 |
| Q13509-2 | ENSG00000258947.8 | ENST00000554444.5 | ENSP00000451617.1 |
| UniProt-id | NM ID | NP ID |
| Q13509-1 | NM_006086.3 | NP_006077.2 |
| Q13509-2 | NM_001197181.1 | NP_001184110.1 |
| Amino acid sequences of our canonical and alternatively spliced TUBB3 |
| accession_id | Protein sequence |
| Q13509-1 | MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPSGNYVGDSDLQLERISVYYNEASSHKYVPRAILVDLEPGTMDSVRSGAFGHLFRPDNF IFGQSGAGNNWAKGHYTEGAELVDSVLDVVRKECENCDCLQGFQLTHSLGGGTGSGMGTLLISKVREEYPDRIMNTFSVVPSPKVSDTVV EPYNATLSIHQLVENTDETYCIDNEALYDICFRTLKLATPTYGDLNHLVSATMSGVTTSLRFPGQLNADLRKLAVNMVPFPRLHFFMPGF APLTARGSQQYRALTVPELTQQMFDAKNMMAACDPRHGRYLTVATVFRGRMSMKEVDEQMLAIQSKNSSYFVEWIPNNVKVAVCDIPPRG LKMSSTFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVSEYQQYQDATAEEEGEMYEDDEEESEAQGPK |
| Q13509-2 | MDSVRSGAFGHLFRPDNFIFGQSGAGNNWAKGHYTEGAELVDSVLDVVRKECENCDCLQGFQLTHSLGGGTGSGMGTLLISKVREEYPDR IMNTFSVVPSPKVSDTVVEPYNATLSIHQLVENTDETYCIDNEALYDICFRTLKLATPTYGDLNHLVSATMSGVTTSLRFPGQLNADLRK LAVNMVPFPRLHFFMPGFAPLTARGSQQYRALTVPELTQQMFDAKNMMAACDPRHGRYLTVATVFRGRMSMKEVDEQMLAIQSKNSSYFV EWIPNNVKVAVCDIPPRGLKMSSTFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVSEYQQYQDATAEE |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TUBB3 (go to UniProt):Q13509 |
| 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 |
| Q13509 | Motif | 1 | 4 | Note=MREI motif;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P07437 | Type=Deletion;Start=1;End=72 |
Gene Isoform Structures and Expression Levels for TUBB3 |
| Gene structures of our canonical and alternative spliced genes of TUBB3 * 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 Q13509-1 |
| 3D view using mol* of Q13509-2 |
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 Q13509-1 |
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| pLDDT distribution across the protein length of Q13509-2 |
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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 Q13509-1 |
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| Ramachandran plot of Q13509-2 |
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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 |
| Q13509-1 | 1.046 | 143 | 1.087 | 379.015 | 0.502 | 0.718 | 0.936 | 0.968 | 0.871 | 1.112 | 0.996 | 23,26,27,215,216,217,224,227,228,231,234,235,270,2 72,273,274,275,276,277,279,282,283,284,288,318,358 ,359,361,362 |
| Q13509-2 | 1.062 | 69 | 1.083 | 160.524 | 0.444 | 0.871 | 1.12 | 2.077 | 0.675 | 3.079 | 0.671 | 163,164,166,167,174,176,177,180,181,184,185,242,24 3,244,278,279,280,294,296 |
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 Q13509-1_Q13509-1_6wsl_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 Q13509-1_6wsl_B_Q13509-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q13509-1_Q13509-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q13509-1_vs_Q13509-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q13509-1_vs_Q13509-2.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 TUBB3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| Q13509 | TUBB3 | DB01873 | Epothilone D | investigational | |
| Q13509 | TUBB3 | DB12695 | Phenethyl Isothiocyanate | investigational | |
| Q13509 | TUBB3 | DB05147 | CYT997 | investigational | |
| Q13509 | TUBB3 | DB06042 | ZEN-012 | investigational | |
| Q13509 | TUBB3 | DB03010 | Patupilone | experimental, investigational | |
| Q13509 | TUBB3 | DB04845 | Ixabepilone | approved, investigational | inhibitor |
Related Diseases to TUBB3 |
| Previous studies relating to the alternative splicing of TUBB3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TUBB3 | 24905733 | Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding. | Tau is the major microtubule-associated protein in neurons involved in microtubule stabilization in the axonal compartment. Changes in tau gene expression, alternative splicing and posttranslational modification regulate tau function and in tauopathies can result in tau mislocalization and dysfunction, causing tau aggregation and cell death. To uncover proteins involved in the development of tauopathies, a yeast two-hybrid system was used to screen for tau-interacting proteins. We show that axotrophin/MARCH7, a RING-variant domain containing protein with similarity to E3 ubiquitin ligases interacts with tau. We defined the tau binding domain to amino acids 552-682 of axotrophin comprising the RING-variant domain. Co-immunoprecipitation and co-localization confirmed the specificity of the interaction. Intracellular localization of axotrophin is determined by an N-terminal nuclear targeting signal and a C-terminal nuclear export signal. In AD brain nuclear localization is lost and axotrophin is rather associated with neurofibrillary tangles. We find here that tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain, which diminishes its microtubule-binding. In vitro ubiquitination of four-repeat tau results in incorporation of up to four ubiquitin molecules compared to two molecules in three-repeat tau. In summary, we present a novel tau modification occurring preferentially on 4-repeat tau protein which modifies microtubule-binding and may impact on the pathogenesis of tauopathies. | D000544 | Alzheimer Disease |
Clinically important variants in TUBB3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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