Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8RX3AJ)

• DOT Name: Carbonic anhydrase-related protein 11 (CA11)
• Synonyms: CA-RP XI; CA-XI; CARP XI; Carbonic anhydrase-related protein 2; CA-RP II; CARP-2
• Gene Name: CA11
• Related Disease:
  Chondrosarcoma
  Congenital alveolar dysplasia
  Dementia
  Glioma
  Neoplasm
  Stomach cancer
  Adenocarcinoma
  Gastrointestinal stromal tumour
  Lung adenocarcinoma
  Advanced cancer
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Neuroblastoma
  Non-small-cell lung cancer
  Spinocerebellar ataxia type 3
• UniProt ID: CAH11_HUMAN
• Pfam ID: PF00194
• Sequence:
  MGAAARLSAPRALVLWAALGAAAHIGPAPDPEDWWSYKDNLQGNFVPGPPFWGLVNAAWS
  LCAVGKRQSPVDVELKRVLYDPFLPPLRLSTGGEKLRGTLYNTGRHVSFLPAPRPVVNVS
  GGPLLYSHRLSELRLLFGARDGAGSEHQINHQGFSAEVQLIHFNQELYGNFSAASRGPNG
  LAILSLFVNVASTSNPFLSRLLNRDTITRISYKNDAYFLQDLSLELLFPESFGFITYQGS
  LSTPPCSETVTWILIDRALNITSLQMHSLRLLSQNPPSQIFQSLSGNSRPLQPLAHRALR
  GNRDPRHPERRCRGPNYRLHVDGVPHGR
• Function: Does not have a catalytic activity.
• Tissue Specificity: Expressed abundantly in the brain with moderate expression also present in spinal cord and thyroid.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chondrosarcoma	DIS4I7JB	Strong	Genetic Variation	[1]
Congenital alveolar dysplasia	DIS1IYUN	Strong	Biomarker	[1]
Dementia	DISXL1WY	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[3]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[4]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Carcinoma	DISH9F1N	Limited	Altered Expression	[5]
Cervical cancer	DISFSHPF	Limited	Biomarker	[6]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[6]
Gastric cancer	DISXGOUK	Limited	Genetic Variation	[1]
Lung cancer	DISCM4YA	Limited	Biomarker	[3]
Lung carcinoma	DISTR26C	Limited	Biomarker	[3]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[7]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[3]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Biomarker	[7]

10 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 Carbonic anhydrase-related protein 11 (CA11).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Carbonic anhydrase-related protein 11 (CA11).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carbonic anhydrase-related protein 11 (CA11).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Carbonic anhydrase-related protein 11 (CA11).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carbonic anhydrase-related protein 11 (CA11).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Carbonic anhydrase-related protein 11 (CA11).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Carbonic anhydrase-related protein 11 (CA11).	[14]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Carbonic anhydrase-related protein 11 (CA11).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Carbonic anhydrase-related protein 11 (CA11).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Carbonic anhydrase-related protein 11 (CA11).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Carbonic anhydrase-related protein 11 (CA11).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Carbonic anhydrase-related protein 11 (CA11).	[15]

References

• [1] BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer.Trends Biochem Sci. 2002 Jul;27(7):329-32. doi: 10.1016/s0968-0004(02)02134-5.
• [2] CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas.Mol Oncol. 2019 May;13(5):1018-1032. doi: 10.1002/1878-0261.12445. Epub 2019 Mar 20.
• [3] Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell lung adenocarcinoma.Virchows Arch. 2006 Jun;448(6):830-7. doi: 10.1007/s00428-006-0199-0. Epub 2006 Apr 12.
• [4] Overexpression of carbonic anhydrase-related protein XI promotes proliferation and invasion of gastrointestinal stromal tumors.Virchows Arch. 2005 Jul;447(1):66-73. doi: 10.1007/s00428-005-1225-3. Epub 2005 Jun 8.
• [5] Expression of carbonic anhydrase-related protein CA-RP VIII in non-small cell lung cancer.Virchows Arch. 2003 Jan;442(1):66-70. doi: 10.1007/s00428-002-0721-y. Epub 2002 Dec 5.
• [6] Human secreted frizzled-related protein is down-regulated and induces apoptosis in human cervical cancer.Exp Cell Res. 2002 Nov 1;280(2):280-7. doi: 10.1006/excr.2002.5649.
• [7] Altered expression of carbonic anhydrase-related protein XI in neuronal cells expressing mutant ataxin-3.Cerebellum. 2013 Jun;12(3):338-49. doi: 10.1007/s12311-012-0430-2.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] 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.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [17] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.