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tubulin beta class I

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Target id: 2640

Nomenclature: tubulin beta class I

Family: Tubulins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 444 6p21.33 TUBB tubulin beta class I
Mouse - 444 17 B1 Tubb5 tubulin, beta 5 class I
Rat - 444 20p12 Tubb5 tubulin, beta 5 class I
Previous and Unofficial Names Click here for help
beta1-tubulin | TUBB5 | tubulin, beta class I | tubulin, beta 5 class I | tubulin
Database Links Click here for help
Alphafold P07437 (Hs), P99024 (Mm), P69897 (Rn)
CATH/Gene3D 3.30.1330.20, 3.40.50.1440
ChEMBL Target CHEMBL5444 (Hs), CHEMBL4739682 (Mm)
DrugBank Target P07437 (Hs)
Ensembl Gene ENSG00000196230 (Hs), ENSMUSG00000001525 (Mm), ENSRNOG00000061216 (Rn)
Entrez Gene 203068 (Hs), 22154 (Mm), 29214 (Rn)
Human Protein Atlas ENSG00000196230 (Hs)
KEGG Gene hsa:203068 (Hs), mmu:22154 (Mm), rno:29214 (Rn)
OMIM 191130 (Hs)
Pharos P07437 (Hs)
RefSeq Nucleotide NM_178014 (Hs), NM_011655 (Mm), NM_173102 (Rn)
RefSeq Protein NP_821133 (Hs), NP_035785 (Mm), NP_775125 (Rn)
UniProtKB P07437 (Hs), P99024 (Mm), P69897 (Rn)
Wikipedia TUBB (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
paclitaxel Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pEC50 8
⤷ pEC50 8.1 (EC50 9x10-9 M) Mitotic cell cycle arrest in A431 cells [8]
vinblastine Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 pIC50
⤷ pIC50 9.0 (IC50 1x10-9 M)
eribulin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.2 pIC50 7
⤷ pIC50 8.2 (IC50 5.9x10-9 M) [7]
colchicine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 1
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [1]
vincristine Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
cabazitaxel Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
docetaxel Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition - -
⤷
ixabepilone Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition - -
⤷
Inhibitor Comments
Tubulin inhibitors take various chemical forms but generally act to inhibit either polymerisation or depolymerisation of tubulin subunits in the formation of microtubules. Polymerisation inhibitors include the Vinca domain compounds (vinblastine, vinblastine, eribulin, monomethyl auristatin E and mertansine) and colchicine which interacts at its own distinct domain on β-tubulin. Depolymerisation inhibitors include the taxol derived drugs (paclitaxel, cabazitaxel and docetaxel) and ixabepilone which all bind to the taxane domain of β-tubulin. The inhibitors listed in the table above are shown in interaction with TUBB (tubulin, beta class I) for clarity, but will also bind other β-tubulin isotypes. It appears that most tubulin inhibitory compounds bind to β-tubulin subunits, but this does not preclude interaction with α-tubulin subunits. For a review of the binding sites determined for the various drug classes, see [6].

Vincristine inhibits tubulin (canine) polymerization in vitro with an IC50 of 500nm [3], and by inference will also inhibit human tubulin polymerization.
Pharmacological data for several of the drugs listed in the Inhibitors table above is unavailable, but the action of theses compounds on microtubule formation, observed as cell-cycle arrest and induction of apoptosis or positive effects against cancer or cancer cell lines, is well established [2,5,9].

Two monoclonal antibodies conjugated with anti-tubulin compounds are also used to treat cancer by interfering with tubulin formation: brentuximab vedotin and trastuzumab emtansine. The monoclonal antibody targets the conjugated drug to specific cells types (CD30+ve cells and ERBB2+ve cells respectively), and once inside the cell the anti-tubulin toxin can set to work, killing the cell.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Tissue Distribution Comments
Leandro-García et al (2010) provide a comprehensive RT-PCR based analysis of the expression of all eight human β-tubulin isotypes across a wide range of tumoral and non-tumoral cell types and tissues [4]
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cortical dysplasia, complex, with other brain malformations 6; CDCBM6
OMIM: 615771

References

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1. Cifuentes M, Schilling B, Ravindra R, Winter J, Janik ME. (2006) Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs. Bioorg Med Chem Lett, 16 (10): 2761-4. [PMID:16504507]

2. Galsky MD, Dritselis A, Kirkpatrick P, Oh WK. (2010) Cabazitaxel. Nat Rev Drug Discov, 9 (9): 677-8. [PMID:20811375]

3. Lavielle G, Hautefaye P, Schaeffer C, Boutin JA, Cudennec CA, Pierré A. (1991) New alpha-amino phosphonic acid derivatives of vinblastine: chemistry and antitumor activity. J Med Chem, 34 (7): 1998-2003. [PMID:2066973]

4. Leandro-García LJ, Leskelä S, Landa I, Montero-Conde C, López-Jiménez E, Letón R, Cascón A, Robledo M, Rodríguez-Antona C. (2010) Tumoral and tissue-specific expression of the major human beta-tubulin isotypes. Cytoskeleton (Hoboken), 67 (4): 214-23. [PMID:20191564]

5. Lee FY, Borzilleri R, Fairchild CR, Kim SH, Long BH, Reventos-Suarez C, Vite GD, Rose WC, Kramer RA. (2001) BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res, 7 (5): 1429-37. [PMID:11350914]

6. Morris PG, Fornier MN. (2008) Microtubule active agents: beyond the taxane frontier. Clin Cancer Res, 14 (22): 7167-72. [PMID:19010832]

7. Narayan S, Carlson EM, Cheng H, Condon K, Du H, Eckley S, Hu Y, Jiang Y, Kumar V, Lewis BM et al.. (2011) Novel second generation analogs of eribulin. Part III: Blood-brain barrier permeability and in vivo activity in a brain tumor model. Bioorg Med Chem Lett, 21 (6): 1639-43. [PMID:21324687]

8. Ouyang X, Piatnitski EL, Pattaropong V, Chen X, He HY, Kiselyov AS, Velankar A, Kawakami J, Labelle M, Smith 2nd L et al.. (2006) Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg Med Chem Lett, 16 (5): 1191-6. [PMID:16377187]

9. Ringel I, Horwitz SB. (1991) Studies with RP 56976 (taxotere): a semisynthetic analogue of taxol. J Natl Cancer Inst, 83 (4): 288-91. [PMID:1671606]

How to cite this page

Tubulins: tubulin beta class I. Last modified on 12/07/2018. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2640.