Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUM7RPJ)

• DOT Name: Guanylate-binding protein 1 (GBP1)
• Synonyms: EC 3.6.1.-; EC 3.6.5.-; GTP-binding protein 1; GBP-1; HuGBP-1; hGBP1; Guanine nucleotide-binding protein 1; Interferon-induced guanylate-binding protein 1
• Gene Name: GBP1
• Related Disease:
  Esophageal squamous cell carcinoma
  Advanced cancer
  Bacillary dysentery
  Bacterial meningitis
  Colorectal neoplasm
  Glioma
  Hepatitis C virus infection
  Inflammatory bowel disease
  Influenza
  Kaposi sarcoma
  Lung adenocarcinoma
  Matthew-Wood syndrome
  McCune-Albright syndrome
  Neoplasm
  Oral cavity squamous cell carcinoma
  Osteoporosis
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Triple negative breast cancer
  Vascular disease
  Epstein barr virus infection
  Breast cancer
  Breast carcinoma
  Cutaneous melanoma
  Melanoma
  Mesothelioma
• UniProt ID: GBP1_HUMAN
• PDB ID: 1DG3; 1F5N; 2B8W; 2B92; 2BC9; 2D4H; 6K1Z; 6K2D; 6LOJ; 8Q4L
• EC Number: 3.6.1.-; 3.6.5.-
• Pfam ID: PF02263 ; PF02841
• Sequence:
  MASEIHMTGPMCLIENTNGRLMANPEALKILSAITQPMVVVAIVGLYRTGKSYLMNKLAG
  KKKGFSLGSTVQSHTKGIWMWCVPHPKKPGHILVLLDTEGLGDVEKGDNQNDSWIFALAV
  LLSSTFVYNSIGTINQQAMDQLYYVTELTHRIRSKSSPDENENEVEDSADFVSFFPDFVW
  TLRDFSLDLEADGQPLTPDEYLTYSLKLKKGTSQKDETFNLPRLCIRKFFPKKKCFVFDR
  PVHRRKLAQLEKLQDEELDPEFVQQVADFCSYIFSNSKTKTLSGGIQVNGPRLESLVLTY
  VNAISSGDLPCMENAVLALAQIENSAAVQKAIAHYEQQMGQKVQLPTETLQELLDLHRDS
  EREAIEVFIRSSFKDVDHLFQKELAAQLEKKRDDFCKQNQEASSDRCSALLQVIFSPLEE
  EVKAGIYSKPGGYRLFVQKLQDLKKKYYEEPRKGIQAEEILQTYLKSKESMTDAILQTDQ
  TLTEKEKEIEVERVKAESAQASAKMLQEMQRKNEQMMEQKERSYQEHLKQLTEKMENDRV
  QLLKEQERTLALKLQEQEQLLKEGFQKESRIMKNEIQDLQTKMRRRKACTIS
• Function: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens. Hydrolyzes GTP to GMP in two consecutive cleavage reactions: GTP is first hydrolyzed to GDP and then to GMP in a processive manner. Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and promotes both inflammasome assembly and autophagy. Acts as a positive regulator of inflammasome assembly by facilitating the detection of inflammasome ligands from pathogens. Involved in the lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol. Following pathogen release in the cytosol, forms a protein coat in a GTPase-dependent manner that encapsulates pathogens and promotes the detection of ligands by pattern recognition receptors. Plays a key role in inflammasome assembly in response to infection by Gram-negative bacteria: following pathogen release in the cytosol, forms a protein coat that encapsulates Gram-negative bacteria and directly binds to lipopolysaccharide (LPS), disrupting the O-antigen barrier and unmasking lipid A that is that detected by the non-canonical inflammasome effector CASP4/CASP11. Also promotes recruitment of proteins that mediate bacterial cytolysis, leading to release double-stranded DNA (dsDNA) that activates the AIM2 inflammasome. Involved in autophagy by regulating bacteriolytic peptide generation via its interaction with ubiquitin-binding protein SQSTM1, which delivers monoubiquitinated proteins to autolysosomes for the generation of bacteriolytic peptides. Confers protection to several pathogens, including the bacterial pathogens L.monocytogenes and M.bovis BCG as well as the protozoan pathogen T.gondii. Exhibits antiviral activity against influenza virus.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway: Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[3]
Bacterial meningitis	DISRP9SL	Strong	Biomarker	[4]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[7]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[8]
Influenza	DIS3PNU3	Strong	Biomarker	[9]
Kaposi sarcoma	DISC1H1Z	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[11]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[12]
McCune-Albright syndrome	DISCO2QT	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Biomarker	[14]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[18]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[19]
Vascular disease	DISVS67S	Strong	Altered Expression	[20]
Epstein barr virus infection	DISOO0WT	moderate	Altered Expression	[21]
Breast cancer	DIS7DPX1	Limited	Biomarker	[22]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[22]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[23]
Melanoma	DIS1RRCY	Limited	Biomarker	[23]
Mesothelioma	DISKWK9M	Limited	Biomarker	[24]

33 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 Guanylate-binding protein 1 (GBP1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Guanylate-binding protein 1 (GBP1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Guanylate-binding protein 1 (GBP1).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanylate-binding protein 1 (GBP1).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Guanylate-binding protein 1 (GBP1).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Guanylate-binding protein 1 (GBP1).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Guanylate-binding protein 1 (GBP1).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Guanylate-binding protein 1 (GBP1).	[32]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Guanylate-binding protein 1 (GBP1).	[33]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Guanylate-binding protein 1 (GBP1).	[33]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Guanylate-binding protein 1 (GBP1).	[34]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Guanylate-binding protein 1 (GBP1).	[35]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Guanylate-binding protein 1 (GBP1).	[36]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Guanylate-binding protein 1 (GBP1).	[34]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Guanylate-binding protein 1 (GBP1).	[37]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Guanylate-binding protein 1 (GBP1).	[34]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Guanylate-binding protein 1 (GBP1).	[34]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Guanylate-binding protein 1 (GBP1).	[38]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Guanylate-binding protein 1 (GBP1).	[39]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Guanylate-binding protein 1 (GBP1).	[40]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Guanylate-binding protein 1 (GBP1).	[34]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Guanylate-binding protein 1 (GBP1).	[41]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Guanylate-binding protein 1 (GBP1).	[34]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Guanylate-binding protein 1 (GBP1).	[42]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Guanylate-binding protein 1 (GBP1).	[43]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Guanylate-binding protein 1 (GBP1).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Guanylate-binding protein 1 (GBP1).	[35]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Guanylate-binding protein 1 (GBP1).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Guanylate-binding protein 1 (GBP1).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Guanylate-binding protein 1 (GBP1).	[46]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Guanylate-binding protein 1 (GBP1).	[47]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Guanylate-binding protein 1 (GBP1).	[48]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Guanylate-binding protein 1 (GBP1).	[49]

References

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• [38] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
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