Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD0CVEC)

• DOT Name: Basigin (BSG)
• Synonyms: 5F7; Collagenase stimulatory factor; Extracellular matrix metalloproteinase inducer; EMMPRIN; Hepatoma-associated antigen; HAb18G; Leukocyte activation antigen M6; OK blood group antigen; Tumor cell-derived collagenase stimulatory factor; TCSF; CD antigen CD147
• Gene Name: BSG
• UniProt ID: BASI_HUMAN
• PDB ID: 3B5H; 3I84; 3I85; 3QQN; 3QR2; 4U0Q; 5X0T; 5XF0; 6LYY; 6LZ0; 7CKO; 7CKR; 7DA5; 7DAA; 7DCE; 7XY8
• Pfam ID: PF13927
• Sequence:
  MAAALFVLLGFALLGTHGASGAAGFVQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFEG
  QGPNDTCSQLWDGARLDRVHIHATYHQHAASTISIDTLVEEDTGTYECRASNDPDRNHLT
  RAPRVKWVRAQAVVLVLEPGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKE
  DALPGQKTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAML
  VCKSESVPPVTDWAWYKITDSEDKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYR
  CNGTSSKGSDQAIITLRVRSHLAALWPFLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDA
  GSAPLKSSGQHQNDKGKNVRQRNSS
• Function: [Isoform 1]: Essential for normal retinal maturation and development. Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors. In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors. May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes ; [Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2; [Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells. Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane. Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling. Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells. Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) ; [Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3. Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte. This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion ; [Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus-associated PPIA/CYPA; [Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA; [Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is not required for SARS-CoV-2 infection; [Isoform 2]: (Microbial infection) Acts as a receptor for measles virus; [Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells.
• Tissue Specificity: .Retina-specific . Expressed in retinal cone photoreceptors (at protein level) .; [Isoform 2]: Expressed in erythrocytes (at protein level) . Highly expressed in melanoma cell lines (at protein level) . Highly expressed in the heart, kidney, skeletal muscle and testis .; [Isoform 3]: Highly expressed in the bone marrow, fetal liver, lung, testis and thymus.; [Isoform 4]: Highly expressed in the bone marrow, fetal liver, lung, testis and thymus.
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway:
  Basigin interactions (R-HSA-210991)
  Integrin cell surface interactions (R-HSA-216083)
  Proton-coupled monocarboxylate transport (R-HSA-433692)
  Defective SLC16A1 causes symptomatic deficiency in lactate transport (SDLT) (R-HSA-5619070)
  Pyruvate metabolism (R-HSA-70268)
  Aspirin ADME (R-HSA-9749641)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Basigin (BSG) decreases the response to substance of Cisplatin.	[25]

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 Basigin (BSG).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Basigin (BSG).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Basigin (BSG).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Basigin (BSG).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Basigin (BSG).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Basigin (BSG).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Basigin (BSG).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Basigin (BSG).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Basigin (BSG).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Basigin (BSG).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Basigin (BSG).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Basigin (BSG).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Basigin (BSG).	[10]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Basigin (BSG).	[11]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Basigin (BSG).	[12]
Carfilzomib	DM48K0X	Approved	Carfilzomib decreases the expression of Basigin (BSG).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Basigin (BSG).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Basigin (BSG).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Basigin (BSG).	[14]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Basigin (BSG).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Basigin (BSG).	[16]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Basigin (BSG).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Basigin (BSG).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Basigin (BSG).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Basigin (BSG).	[21]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Basigin (BSG).	[22]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Basigin (BSG).	[23]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Basigin (BSG).	[24]
Uridine-5'-Monophosphate	DMG1NM7	Investigative	Uridine-5'-Monophosphate decreases the expression of Basigin (BSG).	[23]

References

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• [12] [Resveratrol inhibits expression of EMMPRIN from macrophages]. Yao Xue Xue Bao. 2006 Jul;41(7):625-30.
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• [25] Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to cisplatin in laryngeal carcinoma Hep2 cells. Oncol Rep. 2011 Feb;25(2):425-32. doi: 10.3892/or.2010.1088. Epub 2010 Dec 9.