Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK2SJXR)

• DOT Name: Anaphase-promoting complex subunit 11 (ANAPC11)
• Synonyms: APC11; Cyclosome subunit 11; Hepatocellular carcinoma-associated RING finger protein
• Gene Name: ANAPC11
• Related Disease:
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Neoplasm
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: APC11_HUMAN
• PDB ID: 2MT5; 4R2Y; 4UI9; 5A31; 5G04; 5G05; 5JG6; 5KHR; 5KHU; 5L9T; 5L9U; 5LCW; 6Q6G; 6Q6H; 6TLJ; 6TM5; 6TNT; 7QE7; 8PKP; 8TAR; 8TAU
• Pfam ID: PF12861
• Sequence:
  MKVKIKCWNGVATWLWVANDENCGICRMAFNGCCPDCKVPGDDCPLVWGQCSHCFHMHCI
  LKWLHAQQVQQHCPMCRQEWKFKE
• Function: Together with the cullin protein ANAPC2, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex.
• Tissue Specificity: Expressed at high levels in skeletal muscle and heart; in moderate levels in brain, kidney, and liver; and at low levels in colon, thymus, spleen, small intestine, placenta, lung and peripheral blood leukocyte.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  Ubiquitin mediated proteolysis (hsa04120)
  Progesterone-mediated oocyte maturation (hsa04914)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway:
  APC/C (R-HSA-174048)
  Autodegradation of Cdh1 by Cdh1 (R-HSA-174084)
  APC/C (R-HSA-174154)
  APC/C (R-HSA-174178)
  Cdc20 (R-HSA-174184)
  Conversion from APC/C (R-HSA-176407)
  Regulation of APC/C activators between G1/S and early anaphase (R-HSA-176408)
  APC/C (R-HSA-176409)
  Phosphorylation of the APC/C (R-HSA-176412)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)
  Separation of Sister Chromatids (R-HSA-2467813)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  Assembly of the pre-replicative complex (R-HSA-68867)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  Transcriptional Regulation by VENTX (R-HSA-8853884)
  Aberrant regulation of mitotic exit in cancer due to RB1 defects (R-HSA-9687136)
  Antigen processing (R-HSA-983168)
  Inactivation of APC/C via direct inhibition of the APC/C complex (R-HSA-141430)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Lung squamous cell carcinoma	DISXPIBD	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[4]
Liver cancer	DISDE4BI	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[12]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Anaphase-promoting complex subunit 11 (ANAPC11).	[13]

References

• [1] Overexpression of APC11 predicts worse survival in lung adenocarcinoma.Onco Targets Ther. 2018 Oct 17;11:7125-7132. doi: 10.2147/OTT.S177252. eCollection 2018.
• [2] Contribution of cell culture, RNA extraction, and reverse transcription to the measurement error in quantitative reverse transcription polymerase chain reaction-based gene expression quantification.Anal Biochem. 2009 Oct 1;393(1):29-35. doi: 10.1016/j.ab.2009.06.010. Epub 2009 Jun 13.
• [3] Integrated analysis highlights APC11 protein expression as a likely new independent predictive marker for colorectal cancer.Sci Rep. 2018 May 9;8(1):7386. doi: 10.1038/s41598-018-25631-1.
• [4] Molecular cloning and characterization of a RING-H2 finger protein, ANAPC11, the human homolog of yeast Apc11p.J Cell Biochem. 2001 Aug 1-9;83(2):249-58. doi: 10.1002/jcb.1217.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [10] Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies. Leuk Res. 2008 Feb;32(2):275-85. doi: 10.1016/j.leukres.2007.05.024. Epub 2007 Jul 19.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.