Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAG6HWU)

• DOT Name: Integrin alpha-M (ITGAM)
• Synonyms: CD11 antigen-like family member B; CR-3 alpha chain; Cell surface glycoprotein MAC-1 subunit alpha; Leukocyte adhesion receptor MO1; Neutrophil adherence receptor; CD antigen CD11b
• Gene Name: ITGAM
• UniProt ID: ITAM_HUMAN
• PDB ID: 1BHO; 1BHQ; 1IDN; 1IDO; 1JLM; 1M1U; 1MF7; 1N9Z; 1NA5; 2LKE; 2LKJ; 3Q3G; 3QA3; 4M76; 4XW2; 6RHW; 7AKK; 7P2D; 7USL; 7USM; 8CE6; 8CE9
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF00357 ; PF21520 ; PF00092
• Sequence:
  MALRVLLLTALTLCHGFNLDTENAMTFQENARGFGQSVVQLQGSRVVVGAPQEIVAANQR
  GSLYQCDYSTGSCEPIRLQVPVEAVNMSLGLSLAATTSPPQLLACGPTVHQTCSENTYVK
  GLCFLFGSNLRQQPQKFPEALRGCPQEDSDIAFLIDGSGSIIPHDFRRMKEFVSTVMEQL
  KKSKTLFSLMQYSEEFRIHFTFKEFQNNPNPRSLVKPITQLLGRTHTATGIRKVVRELFN
  ITNGARKNAFKILVVITDGEKFGDPLGYEDVIPEADREGVIRYVIGVGDAFRSEKSRQEL
  NTIASKPPRDHVFQVNNFEALKTIQNQLREKIFAIEGTQTGSSSSFEHEMSQEGFSAAIT
  SNGPLLSTVGSYDWAGGVFLYTSKEKSTFINMTRVDSDMNDAYLGYAAAIILRNRVQSLV
  LGAPRYQHIGLVAMFRQNTGMWESNANVKGTQIGAYFGASLCSVDVDSNGSTDLVLIGAP
  HYYEQTRGGQVSVCPLPRGRARWQCDAVLYGEQGQPWGRFGAALTVLGDVNGDKLTDVAI
  GAPGEEDNRGAVYLFHGTSGSGISPSHSQRIAGSKLSPRLQYFGQSLSGGQDLTMDGLVD
  LTVGAQGHVLLLRSQPVLRVKAIMEFNPREVARNVFECNDQVVKGKEAGEVRVCLHVQKS
  TRDRLREGQIQSVVTYDLALDSGRPHSRAVFNETKNSTRRQTQVLGLTQTCETLKLQLPN
  CIEDPVSPIVLRLNFSLVGTPLSAFGNLRPVLAEDAQRLFTALFPFEKNCGNDNICQDDL
  SITFSFMSLDCLVVGGPREFNVTVTVRNDGEDSYRTQVTFFFPLDLSYRKVSTLQNQRSQ
  RSWRLACESASSTEVSGALKSTSCSINHPIFPENSEVTFNITFDVDSKASLGNKLLLKAN
  VTSENNMPRTNKTEFQLELPVKYAVYMVVTSHGVSTKYLNFTASENTSRVMQHQYQVSNL
  GQRSLPISLVFLVPVRLNQTVIWDRPQVTFSENLSSTCHTKERLPSHSDFLAELRKAPVV
  NCSIAVCQRIQCDIPFFGIQEEFNATLKGNLSFDWYIKTSHNHLLIVSTAEILFNDSVFT
  LLPGQGAFVRSQTETKVEPFEVPNPLPLIVGSSVGGLLLLALITAALYKLGFFKRQYKDM
  MSEGGPPGAEPQ
• Function: Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin ITGAM/ITGB2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration. In association with beta subunit ITGB2/CD18, required for CD177-PRTN3-mediated activation of TNF primed neutrophils. May regulate phagocytosis-induced apoptosis in extravasated neutrophils. May play a role in mast cell development. Required with TYROBP/DAP12 in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development.
• Tissue Specificity: Predominantly expressed in monocytes and granulocytes . Expressed in neutrophils (at protein level) .
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Phagosome (hsa04145)
  Cell adhesion molecules (hsa04514)
  Complement and coagulation cascades (hsa04610)
  Neutrophil extracellular trap formation (hsa04613)
  Hematopoietic cell lineage (hsa04640)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Amoebiasis (hsa05146)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
• Reactome Pathway:
  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

34 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-M (ITGAM).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Integrin alpha-M (ITGAM).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Integrin alpha-M (ITGAM).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Integrin alpha-M (ITGAM).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Integrin alpha-M (ITGAM).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Integrin alpha-M (ITGAM).	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Integrin alpha-M (ITGAM).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Integrin alpha-M (ITGAM).	[9]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Integrin alpha-M (ITGAM).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Integrin alpha-M (ITGAM).	[11]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Integrin alpha-M (ITGAM).	[12]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Integrin alpha-M (ITGAM).	[13]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the expression of Integrin alpha-M (ITGAM).	[14]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Integrin alpha-M (ITGAM).	[15]
Paricalcitol	DMYBV3G	Approved	Paricalcitol increases the expression of Integrin alpha-M (ITGAM).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Integrin alpha-M (ITGAM).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Integrin alpha-M (ITGAM).	[1]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Integrin alpha-M (ITGAM).	[18]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin decreases the expression of Integrin alpha-M (ITGAM).	[19]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Integrin alpha-M (ITGAM).	[20]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Integrin alpha-M (ITGAM).	[21]
Sodium stibogluconate	DMH5MVE	Phase 2	Sodium stibogluconate increases the expression of Integrin alpha-M (ITGAM).	[22]
D-7193	DMO9HWU	Discontinued in Phase 2	D-7193 decreases the expression of Integrin alpha-M (ITGAM).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Integrin alpha-M (ITGAM).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Integrin alpha-M (ITGAM).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Integrin alpha-M (ITGAM).	[25]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Integrin alpha-M (ITGAM).	[26]
	DM9CEI5		increases the expression of Integrin alpha-M (ITGAM).	[6]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of Integrin alpha-M (ITGAM).	[27]
Fmet-leu-phe	DMQ391A	Investigative	Fmet-leu-phe increases the expression of Integrin alpha-M (ITGAM).	[28]
Caffeic acid phenethyl ester	DMRJKIV	Investigative	Caffeic acid phenethyl ester increases the expression of Integrin alpha-M (ITGAM).	[29]
PAF	DMRZAQW	Investigative	PAF increases the expression of Integrin alpha-M (ITGAM).	[30]
Edetic acid	DM10D85	Investigative	Edetic acid increases the expression of Integrin alpha-M (ITGAM).	[31]
KN-62	DMLZ89P	Investigative	KN-62 increases the expression of Integrin alpha-M (ITGAM).	[32]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Integrin alpha-M (ITGAM).	[4]

References

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