Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6G1IAR)

• DOT Name: Integrin beta-1 (ITGB1)
• Synonyms: Fibronectin receptor subunit beta; Glycoprotein IIa; GPIIA; VLA-4 subunit beta; CD antigen CD29
• Gene Name: ITGB1
• UniProt ID: ITB1_HUMAN
• PDB ID: 3G9W; 3T9K; 3VI3; 3VI4; 4DX9; 4WJK; 4WK0; 4WK2; 4WK4; 7CEB; 7CEC; 7NWL; 7NXD
• Pfam ID: PF07974 ; PF18372 ; PF08725 ; PF07965 ; PF00362 ; PF17205
• Sequence:
  MNLQPIFWIGLISSVCCVFAQTDENRCLKANAKSCGECIQAGPNCGWCTNSTFLQEGMPT
  SARCDDLEALKKKGCPPDDIENPRGSKDIKKNKNVTNRSKGTAEKLKPEDITQIQPQQLV
  LRLRSGEPQTFTLKFKRAEDYPIDLYYLMDLSYSMKDDLENVKSLGTDLMNEMRRITSDF
  RIGFGSFVEKTVMPYISTTPAKLRNPCTSEQNCTSPFSYKNVLSLTNKGEVFNELVGKQR
  ISGNLDSPEGGFDAIMQVAVCGSLIGWRNVTRLLVFSTDAGFHFAGDGKLGGIVLPNDGQ
  CHLENNMYTMSHYYDYPSIAHLVQKLSENNIQTIFAVTEEFQPVYKELKNLIPKSAVGTL
  SANSSNVIQLIIDAYNSLSSEVILENGKLSEGVTISYKSYCKNGVNGTGENGRKCSNISI
  GDEVQFEISITSNKCPKKDSDSFKIRPLGFTEEVEVILQYICECECQSEGIPESPKCHEG
  NGTFECGACRCNEGRVGRHCECSTDEVNSEDMDAYCRKENSSEICSNNGECVCGQCVCRK
  RDNTNEIYSGKFCECDNFNCDRSNGLICGGNGVCKCRVCECNPNYTGSACDCSLDTSTCE
  ASNGQICNGRGICECGVCKCTDPKFQGQTCEMCQTCLGVCAEHKECVQCRAFNKGEKKDT
  CTQECSYFNITKVESRDKLPQPVQPDPVSHCKEKDVDDCWFYFTYSVNGNNEVMVHVVEN
  PECPTGPDIIPIVAGVVAGIVLIGLALLLIWKLLMIIHDRREFAKFEKEKMNAKWDTGEN
  PIYKSAVTTVVNPKYEGK
• Function: Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion. Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 and ITGA5:ITGB1 bind to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1. ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling. ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling. Plays an important role in myoblast differentiation and fusion during skeletal myogenesis. ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion. Integrins ITGA9:ITGB1 and ITGA4:ITGB1 repress PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via their interaction with SVEP1, thereby inhibit vasocontraction ; [Isoform 2]: Interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration (in vitro); [Isoform 5]: Isoform 5 displaces isoform 1 in striated muscles; (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8; (Microbial infection) Acts as a receptor for Cytomegalovirus/HHV-5; (Microbial infection) Acts as a receptor for Epstein-Barr virus/HHV-4; (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human parvovirus B19; (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus; (Microbial infection) Acts as a receptor for Mammalian reovirus; (Microbial infection) In case of HIV-1 infection, integrin ITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions; (Microbial infection) Interacts with CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi. Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression ; (Microbial infection) May serve as a receptor for adhesin A (nadA) of N.meningitidis.
• Tissue Specificity: Expressed in vascular smooth muscle cells (at protein level).; [Isoform 1]: Expressed in placenta (at protein level) . Widely expressed, other isoforms are generally coexpressed with a more restricted distribution .; [Isoform 2]: Expressed in skin, liver, skeletal muscle, cardiac muscle, placenta, umbilical vein endothelial cells, neuroblastoma cells, lymphoma cells, hepatoma cells and astrocytoma cells.; [Isoform 3]: Together with isoform 4, is expressed in muscle, kidney, liver, placenta, cervical epithelium, umbilical vein endothelial cells, fibroblast cells, embryonal kidney cells, platelets and several blood cell lines. Expressed in non-proliferating and differentiated prostate gland epithelial cells and in platelets, on the surface of erythroleukemia cells and in various hematopoietic cell lines.; [Isoform 4]: Together with isoform 3, is expressed in muscle, kidney, liver, placenta, cervical epithelium, umbilical vein endothelial cells, fibroblast cells, embryonal kidney cells, platelets and several blood cell lines. Rather than isoform 3, is selectively expressed in peripheral T-cells.; [Isoform 5]: Expressed specifically in striated muscle (skeletal and cardiac muscle).
• KEGG Pathway:
  Virion - Rotavirus (hsa03271)
  Rap1 sig.ling pathway (hsa04015)
  Phagosome (hsa04145)
  PI3K-Akt sig.ling pathway (hsa04151)
  Axon guidance (hsa04360)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cell adhesion molecules (hsa04514)
  Tight junction (hsa04530)
  Platelet activation (hsa04611)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Cytoskeleton in muscle cells (hsa04820)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Pertussis (hsa05133)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Toxoplasmosis (hsa05145)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Small cell lung cancer (hsa05222)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Fibronectin matrix formation (R-HSA-1566977)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Basigin interactions (R-HSA-210991)
  Molecules associated with elastic fibres (R-HSA-2129379)
  Integrin cell surface interactions (R-HSA-216083)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  Laminin interactions (R-HSA-3000157)
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  Other semaphorin interactions (R-HSA-416700)
  Signal transduction by L1 (R-HSA-445144)
  Localization of the PINCH-ILK-PARVIN complex to focal adhesions (R-HSA-446343)
  CHL1 interactions (R-HSA-447041)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  MET activates PTK2 signaling (R-HSA-8874081)
  MET interacts with TNS proteins (R-HSA-8875513)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOG GTPase cycle (R-HSA-9013408)
  RAC3 GTPase cycle (R-HSA-9013423)
  HCMV Early Events (R-HSA-9609690)
  GPER1 signaling (R-HSA-9634597)
  Potential therapeutics for SARS (R-HSA-9679191)
  Elastic fibre formation (R-HSA-1566948)

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
Artesunate	DMR27C8	Approved	Integrin beta-1 (ITGB1) increases the response to substance of Artesunate.	[52]

4 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 Integrin beta-1 (ITGB1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Integrin beta-1 (ITGB1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Integrin beta-1 (ITGB1).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Integrin beta-1 (ITGB1).	[37]

53 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 Integrin beta-1 (ITGB1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Integrin beta-1 (ITGB1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Integrin beta-1 (ITGB1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Integrin beta-1 (ITGB1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Integrin beta-1 (ITGB1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Integrin beta-1 (ITGB1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Integrin beta-1 (ITGB1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Integrin beta-1 (ITGB1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Integrin beta-1 (ITGB1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Integrin beta-1 (ITGB1).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Integrin beta-1 (ITGB1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Integrin beta-1 (ITGB1).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Integrin beta-1 (ITGB1).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Integrin beta-1 (ITGB1).	[16]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Integrin beta-1 (ITGB1).	[17]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Integrin beta-1 (ITGB1).	[18]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Integrin beta-1 (ITGB1).	[19]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Integrin beta-1 (ITGB1).	[14]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Integrin beta-1 (ITGB1).	[20]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Integrin beta-1 (ITGB1).	[21]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Integrin beta-1 (ITGB1).	[22]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Integrin beta-1 (ITGB1).	[6]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Integrin beta-1 (ITGB1).	[23]
Ifosfamide	DMCT3I8	Approved	Ifosfamide affects the expression of Integrin beta-1 (ITGB1).	[6]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Integrin beta-1 (ITGB1).	[24]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Integrin beta-1 (ITGB1).	[25]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Integrin beta-1 (ITGB1).	[26]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Integrin beta-1 (ITGB1).	[27]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Integrin beta-1 (ITGB1).	[28]
Fructose	DM43AN2	Approved	Fructose decreases the expression of Integrin beta-1 (ITGB1).	[29]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol decreases the expression of Integrin beta-1 (ITGB1).	[30]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Integrin beta-1 (ITGB1).	[31]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Integrin beta-1 (ITGB1).	[32]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Integrin beta-1 (ITGB1).	[33]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Integrin beta-1 (ITGB1).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin beta-1 (ITGB1).	[36]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Integrin beta-1 (ITGB1).	[38]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Integrin beta-1 (ITGB1).	[39]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Integrin beta-1 (ITGB1).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Integrin beta-1 (ITGB1).	[41]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Integrin beta-1 (ITGB1).	[42]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Integrin beta-1 (ITGB1).	[43]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Integrin beta-1 (ITGB1).	[29]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Integrin beta-1 (ITGB1).	[44]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Integrin beta-1 (ITGB1).	[45]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Integrin beta-1 (ITGB1).	[46]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Integrin beta-1 (ITGB1).	[48]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Integrin beta-1 (ITGB1).	[49]
Isoarnebin 4	DM0B7NO	Investigative	Isoarnebin 4 decreases the expression of Integrin beta-1 (ITGB1).	[50]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Integrin beta-1 (ITGB1).	[49]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of Integrin beta-1 (ITGB1).	[16]
24(S)-hydroxycholesterol	DMGMWA6	Investigative	24(S)-hydroxycholesterol increases the expression of Integrin beta-1 (ITGB1).	[48]
7alpha-hydroxycholesterol	DMH6LD0	Investigative	7alpha-hydroxycholesterol increases the expression of Integrin beta-1 (ITGB1).	[48]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
	DM9CEI5		decreases the metabolism of Integrin beta-1 (ITGB1).	[47]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
RGD	DMFASRB	Investigative	RGD affects the binding of Integrin beta-1 (ITGB1).	[51]

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