Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA7U2T8)

• DOT Name: Angiogenic factor with G patch and FHA domains 1 (AGGF1)
• Synonyms: Angiogenic factor VG5Q; hVG5Q; G patch domain-containing protein 7; Vasculogenesis gene on 5q protein
• Gene Name: AGGF1
• Related Disease:
  Advanced cancer
  Cardiac failure
  Congestive heart failure
  Fatty liver disease
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hyperglycemia
  Neoplasm
  Peripheral arterial disease
  Primary myelofibrosis
  Stomach cancer
  Vascular disease
  Nervous system disease
  Subarachnoid hemorrhage
  Cardiac disease
  Coronary heart disease
  Hepatocellular carcinoma
  Myocardial infarction
  Vascular malformation
• UniProt ID: AGGF1_HUMAN
• Pfam ID: PF00498 ; PF01585 ; PF17780
• Sequence:
  MASEAPSPPRSPPPPTSPEPELAQLRRKVEKLERELRSCKRQVREIEKLLHHTERLYQNA
  ESNNQELRTQVEELSKILQRGRNEDNKKSDVEVQTENHAPWSISDYFYQTYYNDVSLPNK
  VTELSDQQDQAIETSILNSKDHLQVENDAYPGTDRTENVKYRQVDHFASNSQEPASALAT
  EDTSLEGSSLAESLRAAAEAAVSQTGFSYDENTGLYFDHSTGFYYDSENQLYYDPSTGIY
  YYCDVESGRYQFHSRVDLQPYPTSSTKQSKDKKLKKKRKDPDSSATNEEKDLNSEDQKAF
  SVEHTSCNEEENFANMKKKAKIGIHHKNSPPKVTVPTSGNTIESPLHENISNSTSFKDEK
  IMETDSEPEEGEITDSQTEDSYDEAITSEGNVTAEDSEDEDEDKIWPPCIRVIVIRSPVL
  QIGSLFIITAVNPATIGREKDMEHTLRIPEVGVSKFHAEIYFDHDLQSYVLVDQGSQNGT
  IVNGKQILQPKTKCDPYVLEHGDEVKIGETVLSFHIHPGSDTCDGCEPGQVRAHLRLDKK
  DESFVGPTLSKEEKELERRKELKKIRVKYGLQNTEYEDEKTLKNPKYKDRAGKRREQVGS
  EGTFQRDDAPASVHSEITDSNKGRKMLEKMGWKKGEGLGKDGGGMKTPIQLQLRRTHAGL
  GTGKPSSFEDVHLLQNKNKKNWDKARERFTENFPETKPQKDDPGTMPWVKGTLE
• Function: Promotes angiogenesis and the proliferation of endothelial cells. Able to bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion.
• Tissue Specificity: Widely expressed. Expressed in endothelial cells, vascular smooth muscle cells and osteoblasts. Expressed in umbilical vein endothelial cells and microvascular endothelial cells.
• Reactome Pathway: Signaling by BRAF and RAF1 fusions (R-HSA-6802952)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Peripheral arterial disease	DIS78WFB	Strong	Biomarker	[6]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[7]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]
Vascular disease	DISVS67S	Strong	Genetic Variation	[8]
Nervous system disease	DISJ7GGT	Disputed	Biomarker	[9]
Subarachnoid hemorrhage	DISI7I8Y	Disputed	Altered Expression	[9]
Cardiac disease	DISVO1I5	Limited	Biomarker	[10]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[11]
Myocardial infarction	DIS655KI	Limited	Biomarker	[10]
Vascular malformation	DIS2DB7A	Limited	Biomarker	[12]

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 Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[13]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[19]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[20]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[21]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[19]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Angiogenic factor with G patch and FHA domains 1 (AGGF1).	[26]

References

• [1] Knockdown of AGGF1 inhibits the invasion and migration of gastric cancer via epithelial-mesenchymal transition through Wnt/-catenin pathway.Cancer Cell Int. 2019 Feb 27;19:41. doi: 10.1186/s12935-019-0765-6. eCollection 2019.
• [2] A non-canonical pathway regulates ER stress signaling and blocks ER stress-induced apoptosis and heart failure.Nat Commun. 2017 Jul 25;8(1):133. doi: 10.1038/s41467-017-00171-w.
• [3] Angiogenic factor with G patch and FHA domains 1 (Aggf1) promotes hepatic steatosis in mice.Biochem Biophys Res Commun. 2017 Jan 1;482(1):134-140. doi: 10.1016/j.bbrc.2016.10.071. Epub 2016 Nov 16.
• [4] The Effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 Axis Regulating Glioblastoma Angiogenesis.Front Mol Neurosci. 2018 Jan 9;10:437. doi: 10.3389/fnmol.2017.00437. eCollection 2017.
• [5] Angiogenic Factor AGGF1-Primed Endothelial Progenitor Cells Repair Vascular Defect in Diabetic Mice.Diabetes. 2019 Aug;68(8):1635-1648. doi: 10.2337/db18-1178. Epub 2019 May 15.
• [6] Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model.PLoS One. 2012;7(10):e46998. doi: 10.1371/journal.pone.0046998. Epub 2012 Oct 23.
• [7] X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis.Am J Hematol. 2015 Mar;90(3):E44-8. doi: 10.1002/ajh.23907. Epub 2015 Jan 16.
• [8] Is the E133K allele of VG5Q associated with Klippel-Trenaunay and other overgrowth syndromes?.J Med Genet. 2006 Jul;43(7):613-4. doi: 10.1136/jmg.2006.040790. Epub 2006 Jan 27.
• [9] Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-B pathway after subarachnoid hemorrhage in rats.J Neuroinflammation. 2018 Jun 9;15(1):178. doi: 10.1186/s12974-018-1211-8.
• [10] Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic Angiogenesis for Heart Disease.PLoS Biol. 2016 Aug 11;14(8):e1002529. doi: 10.1371/journal.pbio.1002529. eCollection 2016 Aug.
• [11] LncRNA OR3A4 participates in the angiogenesis of hepatocellular carcinoma through modulating AGGF1/akt/mTOR pathway.Eur J Pharmacol. 2019 Apr 15;849:106-114. doi: 10.1016/j.ejphar.2019.01.049. Epub 2019 Jan 30.
• [12] Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function.J Biol Chem. 2009 Aug 28;284(35):23331-43. doi: 10.1074/jbc.M109.036079. Epub 2009 Jun 25.
• [13] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [20] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [21] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [22] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [23] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [24] 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.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.