Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA66R5E)

• DOT Name: Ras-related protein Rab-6C (RAB6C)
• Synonyms: Rab6-like protein WTH3
• Gene Name: RAB6C
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
• UniProt ID: RAB6C_HUMAN
• Pfam ID: PF00071
• Sequence:
  MSAGGDFGNPLRKFKLVFLGEQSVAKTSLITRFRYDSFDNTYQAIIGIDFLSKTMYLEDG
  TIGLRLWDTAGQERLRSLIPRYIRDSAAAVVVYDITNVNSFQQTTKWIDDVRTERGSDVI
  ITLVGNRTDLADKRQVSVEEGERKAKGLNVTFIETRAKAGYNVKQLFRRVAAALPGMEST
  QDGSREDMSDIKLEKPQEQTVSEGGCSCYSPMSSSTLPQKPPYSFIDCSVNIGLNLFPSL
  ITFCNSSLLPVSWR
• Function: May be involved in the regulation of centrosome duplication and cell cycle progression.
• Tissue Specificity: Highest levels are found in fetal and adult brain, prostate, testis and spinal cord. Undetectable expression in adrenal gland, skeletal muscle, bone marrow, fetal, and adult liver, heart, salivary gland, and trachea. Detected in the HEK293, HEK293T, LNCaP, MCF-7, T-47D and EVSA-T cell lines (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[1]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[1]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Ras-related protein Rab-6C (RAB6C) increases the response to substance of Doxorubicin.	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Ras-related protein Rab-6C (RAB6C).	[2]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Ras-related protein Rab-6C (RAB6C).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras-related protein Rab-6C (RAB6C).	[4]

References

• [1] Epigenetic regulation of WTH3 in primary and cultured drug-resistant breast cancer cells.Cancer Res. 2005 Nov 1;65(21):10024-31. doi: 10.1158/0008-5472.CAN-05-1944.
• [2] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [3] Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression. BMC Cancer. 2008 Nov 7;8:327. doi: 10.1186/1471-2407-8-327.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression. BMC Cancer. 2008 Nov 7;8:327. doi: 10.1186/1471-2407-8-327.