Details of Drug Off-Target (DOT)

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

• DOT Name: Integrin alpha-L (ITGAL)
• Synonyms: CD11 antigen-like family member A; Leukocyte adhesion glycoprotein LFA-1 alpha chain; LFA-1A; Leukocyte function-associated molecule 1 alpha chain; CD antigen CD11a
• Gene Name: ITGAL
• UniProt ID: ITAL_HUMAN
• PDB ID: 1CQP ; 1DGQ ; 1LFA ; 1MJN ; 1MQ8 ; 1MQ9 ; 1MQA ; 1RD4 ; 1T0P ; 1XDD ; 1XDG ; 1XUO ; 1ZON ; 1ZOO ; 1ZOP ; 2ICA ; 2K8O ; 2M3E ; 2O7N ; 3BN3 ; 3BQM ; 3BQN ; 3E2M ; 3EOA ; 3EOB ; 3F74 ; 3F78 ; 3HI6 ; 3M6F ; 3TCX ; 4IXD ; 5E6R ; 5E6S ; 5E6U ; 6BXB ; 6BXF ; 6BXJ ; 6CKB ; 7KC3 ; 7KC5 ; 7KC6
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF00357 ; PF00092
• Sequence:
  MKDSCITVMAMALLSGFFFFAPASSYNLDVRGARSFSPPRAGRHFGYRVLQVGNGVIVGA
  PGEGNSTGSLYQCQSGTGHCLPVTLRGSNYTSKYLGMTLATDPTDGSILACDPGLSRTCD
  QNTYLSGLCYLFRQNLQGPMLQGRPGFQECIKGNVDLVFLFDGSMSLQPDEFQKILDFMK
  DVMKKLSNTSYQFAAVQFSTSYKTEFDFSDYVKRKDPDALLKHVKHMLLLTNTFGAINYV
  ATEVFREELGARPDATKVLIIITDGEATDSGNIDAAKDIIRYIIGIGKHFQTKESQETLH
  KFASKPASEFVKILDTFEKLKDLFTELQKKIYVIEGTSKQDLTSFNMELSSSGISADLSR
  GHAVVGAVGAKDWAGGFLDLKADLQDDTFIGNEPLTPEVRAGYLGYTVTWLPSRQKTSLL
  ASGAPRYQHMGRVLLFQEPQGGGHWSQVQTIHGTQIGSYFGGELCGVDVDQDGETELLLI
  GAPLFYGEQRGGRVFIYQRRQLGFEEVSELQGDPGYPLGRFGEAITALTDINGDGLVDVA
  VGAPLEEQGAVYIFNGRHGGLSPQPSQRIEGTQVLSGIQWFGRSIHGVKDLEGDGLADVA
  VGAESQMIVLSSRPVVDMVTLMSFSPAEIPVHEVECSYSTSNKMKEGVNITICFQIKSLI
  PQFQGRLVANLTYTLQLDGHRTRRRGLFPGGRHELRRNIAVTTSMSCTDFSFHFPVCVQD
  LISPINVSLNFSLWEEEGTPRDQRAQGKDIPPILRPSLHSETWEIPFEKNCGEDKKCEAN
  LRVSFSPARSRALRLTAFASLSVELSLSNLEEDAYWVQLDLHFPPGLSFRKVEMLKPHSQ
  IPVSCEELPEESRLLSRALSCNVSSPIFKAGHSVALQMMFNTLVNSSWGDSVELHANVTC
  NNEDSDLLEDNSATTIIPILYPINILIQDQEDSTLYVSFTPKGPKIHQVKHMYQVRIQPS
  IHDHNIPTLEAVVGVPQPPSEGPITHQWSVQMEPPVPCHYEDLERLPDAAEPCLPGALFR
  CPVVFRQEILVQVIGTLELVGEIEASSMFSLCSSLSISFNSSKHFHLYGSNASLAQVVMK
  VDVVYEKQMLYLYVLSGIGGLLLLLLIFIVLYKVGFFKRNLKEKMEAGRGVPNGIPAEDS
  EQLASGQEAGDPGCLKPLHEKDSESGGGKD
• Function: Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is a receptor for F11R. Integrin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis. Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages.
• Tissue Specificity: Leukocytes.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Cell adhesion molecules (hsa04514)
  Neutrophil extracellular trap formation (hsa04613)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Malaria (hsa05144)
  Staphylococcus aureus infection (hsa05150)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
  Rheumatoid arthritis (hsa05323)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Integrin cell surface interactions (R-HSA-216083)
  Neutrophil degranulation (R-HSA-6798695)
  RUNX3 Regulates Immune Response and Cell Migration (R-HSA-8949275)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

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 Integrin alpha-L (ITGAL).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Integrin alpha-L (ITGAL).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Integrin alpha-L (ITGAL).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Integrin alpha-L (ITGAL).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Integrin alpha-L (ITGAL).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Integrin alpha-L (ITGAL).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Integrin alpha-L (ITGAL).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integrin alpha-L (ITGAL).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Integrin alpha-L (ITGAL).	[7]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Integrin alpha-L (ITGAL).	[8]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Integrin alpha-L (ITGAL).	[9]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Integrin alpha-L (ITGAL).	[10]
Vinblastine	DM5TVS3	Approved	Vinblastine decreases the expression of Integrin alpha-L (ITGAL).	[8]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Integrin alpha-L (ITGAL).	[11]
Etodolac	DM6WJO9	Approved	Etodolac decreases the expression of Integrin alpha-L (ITGAL).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Integrin alpha-L (ITGAL).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin alpha-L (ITGAL).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Integrin alpha-L (ITGAL).	[18]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Integrin alpha-L (ITGAL).	[18]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Integrin alpha-L (ITGAL).	[19]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of Integrin alpha-L (ITGAL).	[19]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Integrin alpha-L (ITGAL).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate affects the localization of Integrin alpha-L (ITGAL).	[14]

References

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