Details of Drug Off-Target (DOT)

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

• DOT Name: Nuclear receptor coactivator 1 (NCOA1)
• Synonyms: NCoA-1; EC 2.3.1.48; Class E basic helix-loop-helix protein 74; bHLHe74; Protein Hin-2; RIP160; Renal carcinoma antigen NY-REN-52; Steroid receptor coactivator 1; SRC-1
• Gene Name: NCOA1
• Related Disease:
  Cognitive impairment
  Gastric adenocarcinoma
  Gastric cancer
  Stomach cancer
  Type-1/2 diabetes
  Aplasia cutis congenita
  Astrocytoma
  B-cell lymphoma
  B-cell neoplasm
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Corpus callosum, agenesis of
  Cutaneous melanoma
  Endometrial cancer
  Estrogen-receptor positive breast cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Hyperglycemia
  Hypothyroidism
  Leiomyoma
  Neoplasm
  Obesity
  Rheumatoid arthritis
  Squamous cell carcinoma
  Urinary bladder neoplasm
  Uterine fibroids
  Clear cell renal carcinoma
  Endometriosis
  Generalized resistance to thyroid hormone
  Glioma
  Melanoma
  Non-hodgkin lymphoma
  Plasma cell myeloma
  Primary cutaneous T-cell lymphoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Carcinoma of liver and intrahepatic biliary tract
  Cholangiocarcinoma
  Endometrial carcinoma
  Liver cancer
  Nasopharyngeal carcinoma
  Prostate neoplasm
  Rhabdomyosarcoma
• UniProt ID: NCOA1_HUMAN
• PDB ID: 1FM6 ; 1FM9 ; 1K4W ; 1K74 ; 1K7L ; 1KV6 ; 1N4H ; 1NQ7 ; 1NRL ; 1P8D ; 1PZL ; 1RDT ; 1TFC ; 1U3R ; 1U3S ; 1X76 ; 1X78 ; 1X7B ; 1X7J ; 1XIU ; 1XV9 ; 1XVP ; 1YY4 ; 1YYE ; 1ZAF ; 2A3I ; 2C52 ; 2FVJ ; 2GTK ; 2HBH ; 2HC4 ; 2HCD ; 2HFP ; 2NPA ; 2NV7 ; 2P54 ; 2PRG ; 3BEJ ; 3BQD ; 3CTB ; 3CWD ; 3DCT ; 3DCU ; 3DR1 ; 3ET1 ; 3ET3 ; 3FEI ; 3FEJ ; 3FUR ; 3FXV ; 3G8I ; 3G9E ; 3GYT ; 3GYU ; 3H0A ; 3HC5 ; 3HC6 ; 3HVL ; 3IPQ ; 3IPS ; 3IPU ; 3KMR ; 3LMP ; 3OKH ; 3OKI ; 3OLF ; 3OLL ; 3OLS ; 3OMK ; 3OMM ; 3OMO ; 3OMP ; 3OMQ ; 3OOF ; 3OOK ; 3P88 ; 3P89 ; 3QT0 ; 3RUT ; 3RUU ; 3RVF ; 3S9S ; 3T03 ; 3UU7 ; 3UUA ; 3UUD ; 3V9Y ; 3VN2 ; 4DK7 ; 4DK8 ; 4DM6 ; 4DM8 ; 4DQM ; 4F9M ; 4FGY ; 4G1D ; 4G1Y ; 4G1Z ; 4G20 ; 4G21 ; 4G2H ; 4HEE ; 4J5X ; 4JYG ; 4JYH ; 4JYI ; 4MG5 ; 4MG6 ; 4MG7 ; 4MG8 ; 4MG9 ; 4MGA ; 4MGB ; 4MGC ; 4MGD ; 4RUJ ; 4RUP ; 4TUZ ; 4TV1 ; 4UDA ; 4UDB ; 4Y29 ; 5A86 ; 5AVI ; 5AVL ; 5AZT ; 5DSH ; 5DV3 ; 5DV6 ; 5DV8 ; 5DVC ; 5DWL ; 5E7V ; 5GTN ; 5GTO ; 5GTP ; 5HJS ; 5JI0 ; 5JMM ; 5L7E ; 5L7G ; 5L7H ; 5MWP ; 5MWY ; 5MX7 ; 5NKY ; 5NMA ; 5NMB ; 5NWM ; 5OW7 ; 5OW9 ; 5OWD ; 5Q0J ; 5Q0K ; 5Q0L ; 5Q0M ; 5Q0N ; 5Q0O ; 5Q0P ; 5Q0Q ; 5Q0R ; 5Q0S ; 5Q0T ; 5Q0U ; 5Q0V ; 5Q0W ; 5Q0X ; 5Q0Y ; 5Q0Z ; 5Q10 ; 5Q11 ; 5Q12 ; 5Q13 ; 5Q14 ; 5Q15 ; 5Q16 ; 5Q18 ; 5Q19 ; 5Q1A ; 5Q1B ; 5Q1C ; 5Q1D ; 5Q1E ; 5Q1F ; 5Q1G ; 5Q1H ; 5Q1I ; 5X0R ; 5X8U ; 5X8W ; 5Y44 ; 5YCN ; 5YCP ; 5YP6 ; 6A5W ; 6A5X ; 6A5Y ; 6A5Z ; 6A60 ; 6BNS ; 6E3G ; 6FO7 ; 6FO8 ; 6FO9 ; 6FOB ; 6FOD ; 6GEV ; 6GG8 ; 6HTY ; 6ICJ ; 6IJR ; 6IJS ; 6ILQ ; 6ITM ; 6JNR ; 6JQ7 ; 6KTM ; 6KTN ; 6L6K ; 6L96 ; 6NX1 ; 6P9F ; 6SSQ ; 6T2M ; 6TFI ; 6U25 ; 6W9H ; 6W9I ; 6XP9 ; 7AOS ; 7B39 ; 7BNS ; 7BNU ; 7BO6 ; 7BPY ; 7BPZ ; 7BQ0 ; 7BQ1 ; 7BQ2 ; 7BQ3 ; 7BQ4 ; 7C6Q ; 7CXF ; 7CXH ; 7CXI ; 7CXJ ; 7CXK ; 7CXL ; 7JYM ; 7KXD ; 7KXE ; 7KXF ; 7OXZ ; 7OY4 ; 7QPI ; 7TRB ; 7WGO ; 7WGP ; 7WGQ ; 7WQQ ; 7XVY ; 7XVZ ; 7XWP ; 7XWQ ; 7XWR ; 7Y8F ; 7Y8G ; 7YFK ; 7ZFG ; 7ZFX ; 8CK5 ; 8CKC ; 8HUK ; 8HUM ; 8HUP ; 8HUQ
• EC Number: 2.3.1.48
• Pfam ID: PF07469 ; PF16665 ; PF08815 ; PF00989 ; PF14598 ; PF08832
• Sequence:
  MSGLGDSSSDPANPDSHKRKGSPCDTLASSTEKRRREQENKYLEELAELLSANISDIDSL
  SVKPDKCKILKKTVDQIQLMKRMEQEKSTTDDDVQKSDISSSSQGVIEKESLGPLLLEAL
  DGFFFVVNCEGRIVFVSENVTSYLGYNQEELMNTSVYSILHVGDHAEFVKNLLPKSLVNG
  VPWPQEATRRNSHTFNCRMLIHPPDEPGTENQEACQRYEVMQCFTVSQPKSIQEDGEDFQ
  SCLICIARRLPRPPAITGVESFMTKQDTTGKIISIDTSSLRAAGRTGWEDLVRKCIYAFF
  QPQGREPSYARQLFQEVMTRGTASSPSYRFILNDGTMLSAHTKCKLCYPQSPDMQPFIMG
  IHIIDREHSGLSPQDDTNSGMSIPRVNPSVNPSISPAHGVARSSTLPPSNSNMVSTRINR
  QQSSDLHSSSHSNSSNSQGSFGCSPGSQIVANVALNQGQASSQSSNPSLNLNNSPMEGTG
  ISLAQFMSPRRQVTSGLATRPRMPNNSFPPNISTLSSPVGMTSSACNNNNRSYSNIPVTS
  LQGMNEGPNNSVGFSASSPVLRQMSSQNSPSRLNIQPAKAESKDNKEIASILNEMIQSDN
  SSSDGKPLDSGLLHNNDRLSDGDSKYSQTSHKLVQLLTTTAEQQLRHADIDTSCKDVLSC
  TGTSNSASANSSGGSCPSSHSSLTERHKILHRLLQEGSPSDITTLSVEPDKKDSASTSVS
  VTGQVQGNSSIKLELDASKKKESKDHQLLRYLLDKDEKDLRSTPNLSLDDVKVKVEKKEQ
  MDPCNTNPTPMTKPTPEEIKLEAQSQFTADLDQFDQLLPTLEKAAQLPGLCETDRMDGAV
  TSVTIKSEILPASLQSATARPTSRLNRLPELELEAIDNQFGQPGTGDQIPWTNNTVTAIN
  QSKSEDQCISSQLDELLCPPTTVEGRNDEKALLEQLVSFLSGKDETELAELDRALGIDKL
  VQGGGLDVLSERFPPQQATPPLIMEERPNLYSQPYSSPSPTANLPSPFQGMVRQKPSLGT
  MPVQVTPPRGAFSPGMGMQPRQTLNRPPAAPNQLRLQLQQRLQGQQQLIHQNRQAILNQF
  AATAPVGINMRSGMQQQITPQPPLNAQMLAQRQRELYSQQHRQRQLIQQQRAMLMRQQSF
  GNNLPPSSGLPVQMGNPRLPQGAPQQFPYPPNYGTNPGTPPASTSPFSQLAANPEASLAN
  RNSMVSRGMTGNIGGQFGTGINPQMQQNVFQYPGAGMVPQGEANFAPSLSPGSSMVPMPI
  PPPQSSLLQQTPPASGYQSPDMKAWQQGAIGNNNVFSQAVQNQPTPAQPGVYNNMSITVS
  MAGGNTNVQNMNPMMAQMQMSSLQMPGMNTVCPEQINDPALRHTGLYCNQLSSTDLLKTE
  ADGTQQVQQVQVFADVQCTVNLVGGDPYLNQPGPLGTQKPTSGPQTPQAQQKSLLQQLLT
  E
• Function: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Estrogen sig.ling pathway (hsa04915)
  Thyroid hormone sig.ling pathway (hsa04919)
  Pathways in cancer (hsa05200)
  Breast cancer (hsa05224)
• Reactome Pathway:
  BMAL1 (R-HSA-1368108)
  Recycling of bile acids and salts (R-HSA-159418)
  Synthesis of bile acids and bile salts (R-HSA-192105)
  Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368)
  Synthesis of bile acids and bile salts via 27-hydroxycholesterol (R-HSA-193807)
  PPARA activates gene expression (R-HSA-1989781)
  Endogenous sterols (R-HSA-211976)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  HATs acetylate histones (R-HSA-3214847)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  SUMOylation of transcription cofactors (R-HSA-3899300)
  Regulation of lipid metabolism by PPARalpha (R-HSA-400206)
  Circadian Clock (R-HSA-400253)
  Estrogen-dependent gene expression (R-HSA-9018519)
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis (R-HSA-9623433)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme signaling (R-HSA-9707616)
  RORA activates gene expression (R-HSA-1368082)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Gastric adenocarcinoma	DISWWLTC	Definitive	Altered Expression	[2]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[2]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Altered Expression	[3]
Aplasia cutis congenita	DISMDAYM	Strong	Biomarker	[4]
Astrocytoma	DISL3V18	Strong	Biomarker	[5]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[6]
B-cell neoplasm	DISVY326	Strong	Biomarker	[7]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Carcinoma	DISH9F1N	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Corpus callosum, agenesis of	DISO9P40	Strong	Biomarker	[4]
Cutaneous melanoma	DIS3MMH9	Strong	Biomarker	[12]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[13]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[14]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[15]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[18]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[19]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Altered Expression	[22]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[24]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[25]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[20]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[26]
Endometriosis	DISX1AG8	moderate	Biomarker	[27]
Generalized resistance to thyroid hormone	DIS4TOK0	moderate	Biomarker	[28]
Glioma	DIS5RPEH	moderate	Altered Expression	[9]
Melanoma	DIS1RRCY	moderate	Altered Expression	[12]
Non-hodgkin lymphoma	DISS2Y8A	moderate	Genetic Variation	[29]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[29]
Primary cutaneous T-cell lymphoma	DIS35WVW	Disputed	Biomarker	[30]
Thyroid cancer	DIS3VLDH	Disputed	Altered Expression	[31]
Thyroid gland carcinoma	DISMNGZ0	Disputed	Altered Expression	[31]
Thyroid tumor	DISLVKMD	Disputed	Altered Expression	[31]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[17]
Cholangiocarcinoma	DIS71F6X	Limited	Altered Expression	[17]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[13]
Liver cancer	DISDE4BI	Limited	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[32]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[10]
Rhabdomyosarcoma	DISNR7MS	Limited	Genetic Variation	[33]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Nuclear receptor coactivator 1 (NCOA1) increases the Renal failure acute ADR of Cisplatin.	[51]
Calcitriol	DM8ZVJ7	Approved	Nuclear receptor coactivator 1 (NCOA1) increases the response to substance of Calcitriol.	[52]
Troglitazone	DM3VFPD	Approved	Nuclear receptor coactivator 1 (NCOA1) increases the response to substance of Troglitazone.	[53]
Clofibrate	DMPC1J7	Approved	Nuclear receptor coactivator 1 (NCOA1) affects the response to substance of Clofibrate.	[54]
IRX4204	DM9SCME	Phase 1	Nuclear receptor coactivator 1 (NCOA1) affects the response to substance of IRX4204.	[54]
Ciglitazone	DMAPO0T	Preclinical	Nuclear receptor coactivator 1 (NCOA1) affects the response to substance of Ciglitazone.	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Nuclear receptor coactivator 1 (NCOA1).	[34]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear receptor coactivator 1 (NCOA1).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nuclear receptor coactivator 1 (NCOA1).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[37]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[39]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[40]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[41]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[42]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[44]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Nuclear receptor coactivator 1 (NCOA1).	[37]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Nuclear receptor coactivator 1 (NCOA1).	[50]

References

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