Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRUMZ8C)

• DOT Name: Double C2-like domain-containing protein beta (DOC2B)
• Synonyms: Doc2-beta
• Gene Name: DOC2B
• Related Disease:
  Hyperglycemia
  Neoplasm
  Type-1 diabetes
  Non-insulin dependent diabetes
  Obesity
• UniProt ID: DOC2B_HUMAN
• Pfam ID: PF00168
• Sequence:
  MTLRRRGEKATISIQEHMAIDVCPGPIRPIKQISDYFPRFPRGLPPDAGPRAAAPPDAPA
  RPAVAGAGRRSPSDGAREDDEDVDQLFGAYGSSPGPSPGPSPARPPAKPPEDEPDADGYE
  SDDCTALGTLDFSLLYDQENNALHCTITKAKGLKPMDHNGLADPYVKLHLLPGASKANKL
  RTKTLRNTLNPTWNETLTYYGITDEDMIRKTLRISVCDEDKFRHNEFIGETRVPLKKLKP
  NHTKTFSICLEKQLPVDKTEDKSLEERGRILISLKYSSQKQGLLVGIVRCAHLAAMDANG
  YSDPYVKTYLRPDVDKKSKHKTAVKKKTLNPEFNEEFCYEIKHGDLAKKSLEVTVWDYDI
  GKSNDFIGGVVLGIHAKGERLKHWFDCLKNKDKRIERWHTLTSELPGAVLSD
• Function: Calcium sensor which positively regulates SNARE-dependent fusion of vesicles with membranes. Binds phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes.
• Tissue Specificity: Widely expressed with highest levels in brain and kidney. Expressed in pancreatic islet cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Type-1 diabetes	DIS7HLUB	Definitive	Altered Expression	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[4]
Obesity	DIS47Y1K	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Double C2-like domain-containing protein beta (DOC2B).	[5]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Double C2-like domain-containing protein beta (DOC2B).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Double C2-like domain-containing protein beta (DOC2B).	[8]

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 Double C2-like domain-containing protein beta (DOC2B).	[7]

References

• [1] Doc2b Protects -Cells Against Inflammatory Damage and Enhances Function.Diabetes. 2018 Jul;67(7):1332-1344. doi: 10.2337/db17-1352. Epub 2018 Apr 16.
• [2] DNA promoter methylation-dependent transcription of the double C2-like domain (DOC2B) gene regulates tumor growth in human cervical cancer.J Biol Chem. 2014 Apr 11;289(15):10637-10649. doi: 10.1074/jbc.M113.491506. Epub 2014 Feb 25.
• [3] Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes.J Clin Endocrinol Metab. 2018 May 1;103(5):1966-1976. doi: 10.1210/jc.2017-02492.
• [4] DOC2B promotes insulin sensitivity in mice via a novel KLC1-dependent mechanism in skeletal muscle.Diabetologia. 2019 May;62(5):845-859. doi: 10.1007/s00125-019-4824-2. Epub 2019 Feb 1.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] 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.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.