Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6GB3WR)

• DOT Name: Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1)
• Synonyms: PGC-1-related coactivator; PRC
• Gene Name: PPRC1
• Related Disease:
  Advanced cancer
  Beta-thalassemia major
  Bone osteosarcoma
  Colorectal neoplasm
  Depression
  Epithelial ovarian cancer
  Ewing sarcoma
  Keratoconus
  Neoplasm
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Rhabdomyosarcoma
  Synovial sarcoma
  Thyroid tumor
  Chronic obstructive pulmonary disease
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
  Dental caries
  Epstein barr virus infection
  Malignant pleural mesothelioma
  Mesothelioma
• UniProt ID: PPRC1_HUMAN
• Pfam ID: PF00076
• Sequence:
  MAARRGRRDGVAPPPSGGPGPDPGGGARGSGWGSRSQAPYGTLGAVSGGEQVLLHEEAGD
  SGFVSLSRLGPSLRDKDLEMEELMLQDETLLGTMQSYMDASLISLIEDFGSLGESRLSLE
  DQNEVSLLTALTEILDNADSENLSPFDSIPDSELLVSPREGSSLHKLLTLSRTPPERDLI
  TPVDPLGPSTGSSRGSGVEMSLPDPSWDFSPPSFLETSSPKLPSWRPPRSRPRWGQSPPP
  QQRSDGEEEEEVASFSGQILAGELDNCVSSIPDFPMHLACPEEEDKATAAEMAVPAAGDE
  SISSLSELVRAMHPYCLPNLTHLASLEDELQEQPDDLTLPEGCVVLEIVGQAATAGDDLE
  IPVVVRQVSPGPRPVLLDDSLETSSALQLLMPTLESETEAAVPKVTLCSEKEGLSLNSEE
  KLDSACLLKPREVVEPVVPKEPQNPPANAAPGSQRARKGRKKKSKEQPAACVEGYARRLR
  SSSRGQSTVGTEVTSQVDNLQKQPQEELQKESGPLQGKGKPRAWARAWAAALENSSPKNL
  ERSAGQSSPAKEGPLDLYPKLADTIQTNPIPTHLSLVDSAQASPMPVDSVEADPTAVGPV
  LAGPVPVDPGLVDLASTSSELVEPLPAEPVLINPVLADSAAVDPAVVPISDNLPPVDAVP
  SGPAPVDLALVDPVPNDLTPVDPVLVKSRPTDPRRGAVSSALGGSAPQLLVESESLDPPK
  TIIPEVKEVVDSLKIESGTSATTHEARPRPLSLSEYRRRRQQRQAETEERSPQPPTGKWP
  SLPETPTGLADIPCLVIPPAPAKKTALQRSPETPLEICLVPVGPSPASPSPEPPVSKPVA
  SSPTEQVPSQEMPLLARPSPPVQSVSPAVPTPPSMSAALPFPAGGLGMPPSLPPPPLQPP
  SLPLSMGPVLPDPFTHYAPLPSWPCYPHVSPSGYPCLPPPPTVPLVSGTPGAYAVPPTCS
  VPWAPPPAPVSPYSSTCTYGPLGWGPGPQHAPFWSTVPPPPLPPASIGRAVPQPKMESRG
  TPAGPPENVLPLSMAPPLSLGLPGHGAPQTEPTKVEVKPVPASPHPKHKVSALVQSPQMK
  ALACVSAEGVTVEEPASERLKPETQETRPREKPPLPATKAVPTPRQSTVPKLPAVHPARL
  RKLSFLPTPRTQGSEDVVQAFISEIGIEASDLSSLLEQFEKSEAKKECPPPAPADSLAVG
  NSGGVDIPQEKRPLDRLQAPELANVAGLTPPATPPHQLWKPLAAVSLLAKAKSPKSTAQE
  GTLKPEGVTEAKHPAAVRLQEGVHGPSRVHVGSGDHDYCVRSRTPPKKMPALVIPEVGSR
  WNVKRHQDITIKPVLSLGPAAPPPPCIAASREPLDHRTSSEQADPSAPCLAPSSLLSPEA
  SPCRNDMNTRTPPEPSAKQRSMRCYRKACRSASPSSQGWQGRRGRNSRSVSSGSNRTSEA
  SSSSSSSSSSSRSRSRSLSPPHKRWRRSSCSSSGRSRRCSSSSSSSSSSSSSSSSSSSSR
  SRSRSPSPRRRSDRRRRYSSYRSHDHYQRQRVLQKERAIEERRVVFIGKIPGRMTRSELK
  QRFSVFGEIEECTIHFRVQGDNYGFVTYRYAEEAFAAIESGHKLRQADEQPFDLCFGGRR
  QFCKRSYSDLDSNREDFDPAPVKSKFDSLDFDTLLKQAQKNLRR
• Function: Acts as a coactivator during transcriptional activation of nuclear genes related to mitochondrial biogenesis and cell growth. Involved in the transcription coactivation of CREB and NRF1 target genes.
• Tissue Specificity: Strongly expressed in heart and skeletal muscle, moderately in lung, placenta, intestine, liver, kidney, spleen, thymus, colon and brain. Also expressed in several oncocytic thyroid tumors.
• Reactome Pathway: Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Beta-thalassemia major	DISW06BV	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[4]
Depression	DIS3XJ69	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Ewing sarcoma	DISQYLV3	Strong	Altered Expression	[3]
Keratoconus	DISOONXH	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[6]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[3]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[3]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[8]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[10]
Prostate cancer	DISF190Y	moderate	Altered Expression	[11]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[11]
Dental caries	DISRBCMD	Limited	Biomarker	[12]
Epstein barr virus infection	DISOO0WT	Limited	Biomarker	[13]
Malignant pleural mesothelioma	DIST2R60	Limited	Altered Expression	[14]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[15]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) affects the response to substance of Methotrexate.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[16]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[28]

16 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 Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[22]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[23]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[22]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[24]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[30]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[31]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[32]
Oxalacetic acid	DMPZSV1	Investigative	Oxalacetic acid increases the expression of Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1).	[33]

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