Details of Drug Off-Target (DOT)

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

DOT Name	Cell division cycle and apoptosis regulator protein 1 (CCAR1)
Synonyms	Cell cycle and apoptosis regulatory protein 1; CARP-1; Death inducer with SAP domain
Gene Name	CCAR1
Related Disease	Breast cancer ( ) Breast carcinoma ( ) T-cell acute lymphoblastic leukaemia ( ) Adult lymphoma ( ) B-cell lymphoma ( ) Breast neoplasm ( ) Cervical cancer ( ) Cervical carcinoma ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Crohn disease ( ) Lymphoma ( ) Lymphoma, non-Hodgkin, familial ( ) Neoplasm ( ) Nicotine dependence ( ) Non-hodgkin lymphoma ( ) Pediatric lymphoma ( ) Renal cell carcinoma ( ) Advanced cancer ( ) Gastric cancer ( ) Hepatocellular carcinoma ( ) Stomach cancer ( ) Lung cancer ( )
UniProt ID	CCAR1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF19257 ; PF14443 ; PF19256 ; PF14444 ; PF02037
Sequence	MAQFGGQKNPPWATQFTATAVSQPAALGVQQPSLLGASPTIYTQQTALAAAGLTTQTPAN YQLTQTAALQQQAAAAAAALQQQYSQPQQALYSVQQQLQQPQQTLLTQPAVALPTSLSLS TPQPTAQITVSYPTPRSSQQQTQPQKQRVFTGVVTKLHDTFGFVDEDVFFQLSAVKGKTP QVGDRVLVEATYNPNMPFKWNAQRIQTLPNQNQSQTQPLLKTPPAVLQPIAPQTTFGVQT QPQPQSLLQAQISAASITPLLQTQPQPLLQQPQQKAGLLQPPVRIVSQPQPARRLDPPSR FSGRNDRGDQVPNRKDDRSRERERERRRSRERSPQRKRSRERSPRRERERSPRRVRRVVP RYTVQFSKFSLDCPSCDMMELRRRYQNLYIPSDFFDAQFTWVDAFPLSRPFQLGNYCNFY VMHREVESLEKNMAILDPPDADHLYSAKVMLMASPSMEDLYHKSCALAEDPQELRDGFQH PARLVKFLVGMKGKDEAMAIGGHWSPSLDGPDPEKDPSVLIKTAIRCCKALTGIDLSVCT QWYRFAEIRYHRPEETHKGRTVPAHVETVVLFFPDVWHCLPTRSEWETLSRGYKQQLVEK LQGERKEADGEQDEEEKDDGEAKEISTPTHWSKLDPKTMKVNDLRKELESRALSSKGLKS QLIARLTKQLKVEEQKEEQKELEKSEKEEDEDDDRKSEDDKEEEERKRQEEIERQRRERR YILPDEPAIIVHPNWAAKSGKFDCSIMSLSVLLDYRLEDNKEHSFEVSLFAELFNEMLQR DFGVRIYKSLLSLPEKEDKKEKDKKSKKDERKDKKEERDDETDEPKPKRRKSGDDKDKKE DRDERKKEDKRKDDSKDDDETEEDNNQDEYDPMEAEEAEDEEDDRDEEEMTKRDDKRDIN RYCKERPSKDKEKEKTQMITINRDLLMAFVYFDQSHCGYLLEKDLEEILYTLGLHLSRAQ VKKLLNKVVLRESCFYRKLTDTSKDEENHEESESLQEDMLGNRLLLPTPTVKQESKDVEE NVGLIVYNGAMVDVGSLLQKLEKSEKVRAEVEQKLQLLEEKTDEDEKTILNLENSNKSLS GELREVKKDLSQLQENLKISENMNLQFENQMNKTIRNLSTVMDEIHTVLKKDNVKNEDKD QKSKENGASV
Function	Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation. May be involved in apoptosis signaling in the presence of the reinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation. In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells. Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells.
Tissue Specificity	Expressed in various epithelial cancer cell lines, including breast, colon, prostate, pancreatic and leukemia. Expression is regulated by growth factors.
Reactome Pathway	mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[2]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[3]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[8]
Lymphoma	DISN6V4S	Strong	Biomarker	[3]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Nicotine dependence	DISZD9W7	Strong	Biomarker	[10]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[3]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[11]
Gastric cancer	DISXGOUK	moderate	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[13]
Stomach cancer	DISKIJSX	moderate	Biomarker	[12]
Lung cancer	DISCM4YA	Disputed	Biomarker	[14]
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⏷ Show the Full List of 24 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

14 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 Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[18]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[20]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[21]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[22]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[20]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[20]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[24]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[26]
JNK-IN-8	DMLWYJB	Investigative	JNK-IN-8 increases the expression of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[5]
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⏷ Show the Full List of 14 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cell division cycle and apoptosis regulator protein 1 (CCAR1).	[25]
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References

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2	Par-4/THAP1 complex and Notch3 competitively regulated pre-mRNA splicing of CCAR1 and affected inversely the survival of T-cell acute lymphoblastic leukemia cells.Oncogene. 2013 Dec 12;32(50):5602-13. doi: 10.1038/onc.2013.349. Epub 2013 Aug 26.
3	Cell cycle and apoptosis regulatory protein (CARP)-1 is a novel, adriamycin-inducible, diffuse large B-cell lymphoma (DLBL) growth suppressor.Cancer Chemother Pharmacol. 2011 Jun;67(6):1401-13. doi: 10.1007/s00280-010-1442-6. Epub 2010 Aug 31.
4	Transactivator of transcription-tagged cell cycle and apoptosis regulatory protein-1 peptides suppress the growth of human breast cancer cells in vitro and in vivo.Mol Cancer Ther. 2007 May;6(5):1661-72. doi: 10.1158/1535-7163.MCT-06-0653.
5	A H2AX?CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage. Cancers (Basel). 2019 Feb 14;11(2):221. doi: 10.3390/cancers11020221.
6	A CARP-1 functional mimetic loaded vitamin E-TPGS micellar nano-formulation for inhibition of renal cell carcinoma.Oncotarget. 2017 Sep 5;8(62):104928-104945. doi: 10.18632/oncotarget.20650. eCollection 2017 Dec 1.
7	Requirement of cell cycle and apoptosis regulator 1 for target gene activation by Wnt and beta-catenin and for anchorage-independent growth of human colon carcinoma cells.J Biol Chem. 2009 Jul 31;284(31):20629-37. doi: 10.1074/jbc.M109.014332. Epub 2009 Jun 11.
8	Anti-TNF Re-induction Is as Effective, Simpler, and Cheaper Compared With Dose Interval Shortening for Secondary Loss of Response in Crohn's Disease.J Crohns Colitis. 2018 Feb 28;12(3):280-288. doi: 10.1093/ecco-jcc/jjx144.
9	Mutually exclusive acetylation and ubiquitylation of the splicing factor SRSF5 control tumor growth.Nat Commun. 2018 Jun 25;9(1):2464. doi: 10.1038/s41467-018-04815-3.
10	Persistence of cigarette smoking: familial liability and the role of nicotine dependence.Addiction. 2002 Aug;97(8):1063-70. doi: 10.1046/j.1360-0443.2002.00211.x.
11	Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.PLoS One. 2014 Jul 17;9(7):e102567. doi: 10.1371/journal.pone.0102567. eCollection 2014.
12	Inhibition of CCAR1, a Coactivator of -Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells.Int J Mol Sci. 2017 Feb 21;18(2):460. doi: 10.3390/ijms18020460.
13	Cell Cycle and Apoptosis Regulator 1, CCAR1, Regulates Enhancer-Dependent Nuclear Receptor CAR Transactivation.Mol Pharmacol. 2019 Jan;95(1):120-126. doi: 10.1124/mol.118.114272. Epub 2018 Nov 5.
14	A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers.Oncotarget. 2018 Jul 3;9(51):29680-29697. doi: 10.18632/oncotarget.25671. eCollection 2018 Jul 3.
15	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
16	CARP-1 functional mimetics: a novel class of small molecule inhibitors of medulloblastoma cell growth. PLoS One. 2013 Jun 24;8(6):e66733. doi: 10.1371/journal.pone.0066733. Print 2013.
17	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
18	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
19	Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
20	Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
21	Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem. 2011 Nov;357(1-2):83-94. doi: 10.1007/s11010-011-0878-2. Epub 2011 May 19.
22	Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
23	Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
24	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
25	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
26	Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
27	A H2AX?CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage. Cancers (Basel). 2019 Feb 14;11(2):221. doi: 10.3390/cancers11020221.