Details of Drug Off-Target (DOT)

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

• DOT Name: Nuclear receptor coactivator 6 (NCOA6)
• Synonyms: Activating signal cointegrator 2; ASC-2; Amplified in breast cancer protein 3; Cancer-amplified transcriptional coactivator ASC-2; Nuclear receptor coactivator RAP250; NRC RAP250; Nuclear receptor-activating protein, 250 kDa; Peroxisome proliferator-activated receptor-interacting protein; PPAR-interacting protein; PRIP; Thyroid hormone receptor-binding protein
• Gene Name: NCOA6
• Related Disease:
  Adenoma
  Advanced cancer
  Alcohol dependence
  Alzheimer disease
  Astrocytoma
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cardiac disease
  Cataract
  Clear cell renal carcinoma
  Constipation
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Endometriosis
  Gerstmann-Straussler-Scheinker syndrome
  Intellectual disability
  Liver cirrhosis
  Lung cancer
  Melanoma
  Mental disorder
  Neoplasm
  Non-insulin dependent diabetes
  Prostate carcinoma
  Renal cell carcinoma
  Schizophrenia
  Venous thromboembolism
  Wilms tumor
  Coronary heart disease
  Small lymphocytic lymphoma
  Meningitis
  Prostate cancer
• UniProt ID: NCOA6_HUMAN
• Pfam ID: PF13820
• Sequence:
  MVLDDLPNLEDIYTSLCSSTMEDSEMDFDSGLEDDDTKSDSILEDSTIFVAFKGNIDDKD
  FKWKLDAILKNVPNLLHMESSKLKVQKVEPWNSVRVTFNIPREAAERLRILAQSNNQQLR
  DLGILSVQIEGEGAINLALAQNRSQDVRMNGPMGAGNSVRMEAGFPMASGPGIIRMNNPA
  TVMIPPGGNVSSSMMAPGPNPELQPRTPRPASQSDAMDPLLSGLHIQQQSHPSGSLAPPH
  HPMQPVSVNRQMNPANFPQLQQQQQQQQQQQQQQQQQQQQQQQQQLQARPPQQHQQQQPQ
  GIRPQFTAPTQVPVPPGWNQLPSGALQPPPAQGSLGTMTANQGWKKAPLPGPMQQQLQAR
  PSLATVQTPSHPPPPYPFGSQQASQAHTNFPQMSNPGQFTAPQMKSLQGGPSRVPTPLQQ
  PHLTNKSPASSPSSFQQGSPASSPTVNQTQQQMGPRPPQNNPLPQGFQQPVSSPGRNPMV
  QQGNVPPNFMVMQQQPPNQGPQSLHPGLGGMPKRLPPGFSAGQANPNFMQGQVPSTTATT
  PGNSGAPQLQANQNVQHAGGQGAGPPQNQMQVSHGPPNMMQPSLMGIHGNMNNQQAGTSG
  VPQVNLSNMQGQPQQGPPSQLMGMHQQIVPSQGQMVQQQGTLNPQNPMILSRAQLMPQGQ
  MMVNPPSQNLGPSPQRMTPPKQMLSQQGPQMMAPHNQMMGPQGQVLLQQNPMIEQIMTNQ
  MQGNKQQFNTQNQSNVMPGPAQIMRGPTPNMQGNMVQFTGQMSGQMLPQQGPVNNSPSQV
  MGIQGQVLRPPGPSPHMAQQHGDPATTANNDVSLSQMMPDVSIQQTNMVPPHVQAMQGNS
  ASGNHFSGHGMSFNAPFSGAPNGNQMSCGQNPGFPVNKDVTLTSPLLVNLLQSDISAGHF
  GVNNKQNNTNANKPKKKKPPRKKKNSQQDLNTPDTRPAGLEEADQPPLPGEQGINLDNSG
  PKLPEFSNRPPGYPSQPVEQRPLQQMPPQLMQHVAPPPQPPQQQPQPQLPQQQQPPPPSQ
  PQSQQQQQQQQQMMMMLMMQQDPKSVRLPVSQNVHPPRGPLNPDSQRMPMQQSGSVPVMV
  SLQGPASVPPSPDKQRMPMPVNTPLGSNSRKMVYQESPQNPSSSPLAEMASLPEASGSEA
  PSVPGGPNNMPSHVVLPQNQLMMTGPKPGPSPLSATQGATPQQPPVNSLPSSHGHHFPNV
  AAPTQTSRPKTPNRASPRPYYPQTPNNRPPSTEPSEISLSPERLNASIAGLFPPQINIPL
  PPRPNLNRGFDQQGLNPTTLKAIGQAPSNLTMNPSNFATPQTHKLDSVVVNSGKQSNSGA
  TKRASPSNSRRSSPGSSRKTTPSPGRQNSKAPKLTLASQTNAALLQNVELPRNVLVSPTP
  LANPPVPGSFPNNSGLNPQNSTVSVAAVGGVVEDNKESLNVPQDSDCQNSQSRKEQVNIE
  LKAVPAQEVKMVVPEDQSKKDGQPSDPNKLPSVEENKNLVSPAMREAPTSLSQLLDNSGA
  PNVTIKPPGLTDLEVTPPVVSGEDLKKASVIPTLQDLSSSKEPSNSLNLPHSNELCSSLV
  HPELSEVSSNVAPSIPPVMSRPVSSSSISTPLPPNQITVFVTSNPITTSANTSAALPTHL
  QSALMSTVVTMPNAGSKVMVSEGQSAAQSNARPQFITPVFINSSSIIQVMKGSQPSTIPA
  APLTTNSGLMPPSVAVVGPLHIPQNIKFSSAPVPPNALSSSPAPNIQTGRPLVLSSRATP
  VQLPSPPCTSSPVVPSHPPVQQVKELNPDEASPQVNTSADQNTLPSSQSTTMVSPLLTNS
  PGSSGNRRSPVSSSKGKGKVDKIGQILLTKACKKVTGSLEKGEEQYGADGETEGQGLDTT
  APGLMGTEQLSTELDSKTPTPPAPTLLKMTSSPVGPGTASAGPSLPGGALPTSVRSIVTT
  LVPSELISAVPTTKSNHGGIASESLAGGLVEEKVGSHPELLPSIAPSQNLVSKETSTTAL
  QASVARPELEVNAAIVSGQSSEPKEIVEKSKIPGRRNSRTEEPTVASESVENGHRKRSSR
  PASASSSTKDITSAVQSKRRKSK
• Function: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Coactivates expression in an agonist- and AF2-dependent manner. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Probably functions as a general coactivator, rather than just a nuclear receptor coactivator. May also be involved in the coactivation of the NF-kappa-B pathway. May coactivate expression via a remodeling of chromatin and its interaction with histone acetyltransferase proteins.
• Tissue Specificity: Ubiquitous. Highly expressed in brain, prostate, testis and ovary; weakly expressed in lung, thymus and small intestine.
• Reactome Pathway:
  BMAL1 (R-HSA-1368108)
  PPARA activates gene expression (R-HSA-1989781)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Regulation of lipid metabolism by PPARalpha (R-HSA-400206)
  Circadian Clock (R-HSA-400253)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme signaling (R-HSA-9707616)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  RORA activates gene expression (R-HSA-1368082)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[9]
Cataract	DISUD7SL	Strong	Biomarker	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Constipation	DISRQXWI	Strong	Biomarker	[12]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[9]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Endometriosis	DISX1AG8	Strong	Biomarker	[13]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Genetic Variation	[14]
Intellectual disability	DISMBNXP	Strong	Biomarker	[6]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[15]
Lung cancer	DISCM4YA	Strong	Altered Expression	[16]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[17]
Mental disorder	DIS3J5R8	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[20]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[21]
Wilms tumor	DISB6T16	Strong	Altered Expression	[22]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[23]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[24]
Meningitis	DISQABAA	Limited	Biomarker	[25]
Prostate cancer	DISF190Y	Limited	Altered Expression	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Nuclear receptor coactivator 6 (NCOA6).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear receptor coactivator 6 (NCOA6).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nuclear receptor coactivator 6 (NCOA6).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Nuclear receptor coactivator 6 (NCOA6).	[30]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nuclear receptor coactivator 6 (NCOA6).	[27]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Nuclear receptor coactivator 6 (NCOA6).	[31]
Marinol	DM70IK5	Approved	Marinol increases the expression of Nuclear receptor coactivator 6 (NCOA6).	[32]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear receptor coactivator 6 (NCOA6).	[33]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Nuclear receptor coactivator 6 (NCOA6).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nuclear receptor coactivator 6 (NCOA6).	[34]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Nuclear receptor coactivator 6 (NCOA6).	[35]

References

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