Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBT6W48)

• DOT Name: Tubulin beta chain
• Synonyms: Tubulin beta-5 chain
• Gene Name: TUBB
• Related Disease:
  Complex cortical dysplasia with other brain malformations 6
  Multiple benign circumferential skin creases on limbs 1
  TUBB3-related tubulinopathy
  Multiple benign circumferential skin creases on limbs
• UniProt ID: TBB5_HUMAN
• PDB ID: 3QNZ; 3QO0; 5N5N; 6I2I; 6QUS; 6QUY; 6QVE; 6QVJ; 7TRG; 7TTN; 7TTT; 7TUB; 7X0S; 8BPO
• Pfam ID: PF00091 ; PF03953
• Sequence:
  MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGTYHGDSDLQLDRISVYYNEATGGKYV
  PRAILVDLEPGTMDSVRSGPFGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDSVLDVV
  RKEAESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEYPDRIMNTFSVVPSPKVSDTVV
  EPYNATLSVHQLVENTDETYCIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCL
  RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQVFDAKNMM
  AACDPRHGRYLTVAAVFRGRMSMKEVDEQMLNVQNKNSSYFVEWIPNNVKTAVCDIPPRG
  LKMAVTFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVS
  EYQQYQDATAEEEEDFGEEAEEEA
• Function: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
• Tissue Specificity: Ubiquitously expressed with highest levels in spleen, thymus and immature brain.
• KEGG Pathway:
  Phagosome (hsa04145)
  Gap junction (hsa04540)
  Motor proteins (hsa04814)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  Neutrophil degranulation (R-HSA-6798695)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Potential therapeutics for SARS (R-HSA-9679191)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex cortical dysplasia with other brain malformations 6	DISV3YBR	Definitive	Autosomal dominant	[1]
Multiple benign circumferential skin creases on limbs 1	DIS6BAPZ	Definitive	Autosomal dominant	[2]
TUBB3-related tubulinopathy	DISFVM5K	Definitive	Autosomal dominant	[1]
Multiple benign circumferential skin creases on limbs	DISZB59K	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Tubulin beta chain increases the response to substance of Paclitaxel.	[42]

39 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tubulin beta chain.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tubulin beta chain.	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tubulin beta chain.	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tubulin beta chain.	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tubulin beta chain.	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin beta chain.	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tubulin beta chain.	[10]
Marinol	DM70IK5	Approved	Marinol affects the expression of Tubulin beta chain.	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tubulin beta chain.	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tubulin beta chain.	[13]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Tubulin beta chain.	[14]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Tubulin beta chain.	[15]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Tubulin beta chain.	[16]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Tubulin beta chain.	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Tubulin beta chain.	[18]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Tubulin beta chain.	[19]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Tubulin beta chain.	[17]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Tubulin beta chain.	[20]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Tubulin beta chain.	[17]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Tubulin beta chain.	[21]
Docetaxel	DMDI269	Approved	Docetaxel increases the expression of Tubulin beta chain.	[22]
Dopamine	DMPGUCF	Approved	Dopamine decreases the expression of Tubulin beta chain.	[23]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Tubulin beta chain.	[24]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tubulin beta chain.	[25]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Tubulin beta chain.	[26]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Tubulin beta chain.	[27]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of Tubulin beta chain.	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tubulin beta chain.	[29]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tubulin beta chain.	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tubulin beta chain.	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tubulin beta chain.	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tubulin beta chain.	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tubulin beta chain.	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tubulin beta chain.	[35]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tubulin beta chain.	[36]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Tubulin beta chain.	[38]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Tubulin beta chain.	[39]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Tubulin beta chain.	[40]
biochanin A	DM0HPWY	Investigative	biochanin A increases the expression of Tubulin beta chain.	[41]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tubulin beta chain.	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tubulin beta chain.	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Tubulin beta chain.	[37]

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