Details of Drug Off-Target (DOT)

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

• DOT Name: Integrin beta-2 (ITGB2)
• Synonyms: Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta; Complement receptor C3 subunit beta; CD antigen CD18
• Gene Name: ITGB2
• Related Disease: Leukocyte adhesion deficiency type 1
• UniProt ID: ITB2_HUMAN
• PDB ID: 1L3Y; 1YUK; 2JF1; 2P26; 2P28; 2V7D; 3K6S; 3K71; 3K72; 4NEH; 4NEN; 5E6R; 5E6S; 5E6U; 5E6V; 5E6W; 5E6X; 5ES4; 5XR1; 5ZAZ; 7P2D; 7USL; 7USM
• Pfam ID: PF08725 ; PF07965 ; PF00362 ; PF17205
• Sequence:
  MLGLRPPLLALVGLLSLGCVLSQECTKFKVSSCRECIESGPGCTWCQKLNFTGPGDPDSI
  RCDTRPQLLMRGCAADDIMDPTSLAETQEDHNGGQKQLSPQKVTLYLRPGQAAAFNVTFR
  RAKGYPIDLYYLMDLSYSMLDDLRNVKKLGGDLLRALNEITESGRIGFGSFVDKTVLPFV
  NTHPDKLRNPCPNKEKECQPPFAFRHVLKLTNNSNQFQTEVGKQLISGNLDAPEGGLDAM
  MQVAACPEEIGWRNVTRLLVFATDDGFHFAGDGKLGAILTPNDGRCHLEDNLYKRSNEFD
  YPSVGQLAHKLAENNIQPIFAVTSRMVKTYEKLTEIIPKSAVGELSEDSSNVVHLIKNAY
  NKLSSRVFLDHNALPDTLKVTYDSFCSNGVTHRNQPRGDCDGVQINVPITFQVKVTATEC
  IQEQSFVIRALGFTDIVTVQVLPQCECRCRDQSRDRSLCHGKGFLECGICRCDTGYIGKN
  CECQTQGRSSQELEGSCRKDNNSIICSGLGDCVCGQCLCHTSDVPGKLIYGQYCECDTIN
  CERYNGQVCGGPGRGLCFCGKCRCHPGFEGSACQCERTTEGCLNPRRVECSGRGRCRCNV
  CECHSGYQLPLCQECPGCPSPCGKYISCAECLKFEKGPFGKNCSAACPGLQLSNNPVKGR
  TCKERDSEGCWVAYTLEQQDGMDRYLIYVDESRECVAGPNIAAIVGGTVAGIVLIGILLL
  VIWKALIHLSDLREYRRFEKEKLKSQWNNDNPLFKSATTTVMNPKFAES
• Function: Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation. Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils.
• Tissue Specificity: Leukocytes . Expressed in neutrophils (at protein level) .
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Phagosome (hsa04145)
  Hippo sig.ling pathway (hsa04390)
  Cell adhesion molecules (hsa04514)
  Complement and coagulation cascades (hsa04610)
  Neutrophil extracellular trap formation (hsa04613)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Malaria (hsa05144)
  Amoebiasis (hsa05146)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Rheumatoid arthritis (hsa05323)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Integrin cell surface interactions (R-HSA-216083)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Neutrophil degranulation (R-HSA-6798695)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukocyte adhesion deficiency type 1	DISA1J7W	Definitive	Autosomal recessive	[1]

1 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 Integrin beta-2 (ITGB2).	[2]

28 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-2 (ITGB2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Integrin beta-2 (ITGB2).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Integrin beta-2 (ITGB2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integrin beta-2 (ITGB2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Integrin beta-2 (ITGB2).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Integrin beta-2 (ITGB2).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Integrin beta-2 (ITGB2).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Integrin beta-2 (ITGB2).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Integrin beta-2 (ITGB2).	[11]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Integrin beta-2 (ITGB2).	[12]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Integrin beta-2 (ITGB2).	[13]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Integrin beta-2 (ITGB2).	[14]
Josamycin	DMKJ8LB	Approved	Josamycin decreases the expression of Integrin beta-2 (ITGB2).	[15]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Integrin beta-2 (ITGB2).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Integrin beta-2 (ITGB2).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Integrin beta-2 (ITGB2).	[18]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Integrin beta-2 (ITGB2).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Integrin beta-2 (ITGB2).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin beta-2 (ITGB2).	[21]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Integrin beta-2 (ITGB2).	[22]
PMID28870136-Compound-49	DMTUC9E	Patented	PMID28870136-Compound-49 affects the expression of Integrin beta-2 (ITGB2).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Integrin beta-2 (ITGB2).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Integrin beta-2 (ITGB2).	[25]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Integrin beta-2 (ITGB2).	[26]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Integrin beta-2 (ITGB2).	[20]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Integrin beta-2 (ITGB2).	[20]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Integrin beta-2 (ITGB2).	[20]
Fmet-leu-phe	DMQ391A	Investigative	Fmet-leu-phe increases the expression of Integrin beta-2 (ITGB2).	[27]

References

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