Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7IG7HT)

• DOT Name: Proliferation-associated protein 2G4 (PA2G4)
• Synonyms: Cell cycle protein p38-2G4 homolog; hG4-1; ErbB3-binding protein 1
• Gene Name: PA2G4
• Related Disease:
  Brain neoplasm
  Haematological malignancy
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Bladder cancer
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Dilated cardiomyopathy 1A
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Metabolic disorder
  Metastatic prostate carcinoma
  Neuroblastoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Influenza
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland follicular carcinoma
  Thyroid tumor
  Gallbladder cancer
  Gallbladder carcinoma
  Advanced cancer
  Aplasia cutis congenita
  Corpus callosum, agenesis of
• UniProt ID: PA2G4_HUMAN
• PDB ID: 2Q8K; 3J2I; 6CHT; 6LSR; 6SXO; 6WM8; 6Z6L; 6Z6M; 6Z6N; 6ZM7; 6ZME; 6ZMI; 6ZMO; 7BHP
• Pfam ID: PF00557
• Sequence:
  MSGEDEQQEQTIAEDLVVTKYKMGGDIANRVLRSLVEASSSGVSVLSLCEKGDAMIMEET
  GKIFKKEKEMKKGIAFPTSISVNNCVCHFSPLKSDQDYILKEGDLVKIDLGVHVDGFIAN
  VAHTFVVDVAQGTQVTGRKADVIKAAHLCAEAALRLVKPGNQNTQVTEAWNKVAHSFNCT
  PIEGMLSHQLKQHVIDGEKTIIQNPTDQQKKDHEKAEFEVHEVYAVDVLVSSGEGKAKDA
  GQRTTIYKRDPSKQYGLKMKTSRAFFSEVERRFDAMPFTLRAFEDEKKARMGVVECAKHE
  LLQPFNVLYEKEGEFVAQFKFTVLLMPNGPMRITSGPFEPDLYKSEMEVQDAELKALLQS
  SASRKTQKKKKKKASKTAENATSGETLEENEAGD
• Function: May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly. Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site). Regulates cell proliferation, differentiation, and survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes cell differentiation.
• Tissue Specificity: Isoform 2 is undetectable whereas isoform 1 is strongly expressed in cancer cells (at protein level). Isoform 1 and isoform 2 are widely expressed, including heart, brain, lung, pancreas, skeletal muscle, kidney, placenta and liver.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain neoplasm	DISY3EKS	Definitive	Biomarker	[1]
Haematological malignancy	DISCDP7W	Definitive	Altered Expression	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[10]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[10]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[11]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[12]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[14]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[15]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[11]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[4]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[16]
Breast cancer	DIS7DPX1	moderate	Biomarker	[17]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[17]
Colon cancer	DISVC52G	moderate	Biomarker	[18]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[19]
Influenza	DIS3PNU3	moderate	Biomarker	[20]
Matthew-Wood syndrome	DISA7HR7	moderate	Altered Expression	[21]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[21]
Thyroid cancer	DIS3VLDH	moderate	Biomarker	[22]
Thyroid gland carcinoma	DISMNGZ0	moderate	Biomarker	[22]
Thyroid gland follicular carcinoma	DISFK2QT	moderate	Altered Expression	[22]
Thyroid tumor	DISLVKMD	moderate	Altered Expression	[22]
Gallbladder cancer	DISXJUAF	Disputed	Biomarker	[23]
Gallbladder carcinoma	DISD6ACL	Disputed	Biomarker	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[13]
Aplasia cutis congenita	DISMDAYM	Limited	Biomarker	[14]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bicalutamide	DMZMSPF	Approved	Proliferation-associated protein 2G4 (PA2G4) increases the response to substance of Bicalutamide.	[46]

21 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 Proliferation-associated protein 2G4 (PA2G4).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[26]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[28]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[29]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Proliferation-associated protein 2G4 (PA2G4).	[30]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[31]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of Proliferation-associated protein 2G4 (PA2G4).	[32]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[33]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[34]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[29]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[35]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[27]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[36]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[40]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Proliferation-associated protein 2G4 (PA2G4).	[43]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[44]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Proliferation-associated protein 2G4 (PA2G4).	[45]

3 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 increases the sumoylation of Proliferation-associated protein 2G4 (PA2G4).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Proliferation-associated protein 2G4 (PA2G4).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Proliferation-associated protein 2G4 (PA2G4).	[42]

References

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• [45] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
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