Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTB69FJ)

• DTT Name: Integrin alpha-M (ITGAM)
• Synonyms: Neutrophil adherence receptor; Leukocyte adhesion receptor MO1; Cell surface glycoprotein Mac-1; Cell surface glycoprotein MAC-1 subunit alpha; Cell surface glycoprotein MAC-1 alpha subunit; CR3A; CR-3 alpha chain; CD11b; CD11 antigen-like family member B
• Gene Name: ITGAM
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Integrin
• UniProt ID: ITAM_HUMAN
• TTD ID: T95616
• Sequence:
  MALRVLLLTALTLCHGFNLDTENAMTFQENARGFGQSVVQLQGSRVVVGAPQEIVAANQR
  GSLYQCDYSTGSCEPIRLQVPVEAVNMSLGLSLAATTSPPQLLACGPTVHQTCSENTYVK
  GLCFLFGSNLRQQPQKFPEALRGCPQEDSDIAFLIDGSGSIIPHDFRRMKEFVSTVMEQL
  KKSKTLFSLMQYSEEFRIHFTFKEFQNNPNPRSLVKPITQLLGRTHTATGIRKVVRELFN
  ITNGARKNAFKILVVITDGEKFGDPLGYEDVIPEADREGVIRYVIGVGDAFRSEKSRQEL
  NTIASKPPRDHVFQVNNFEALKTIQNQLREKIFAIEGTQTGSSSSFEHEMSQEGFSAAIT
  SNGPLLSTVGSYDWAGGVFLYTSKEKSTFINMTRVDSDMNDAYLGYAAAIILRNRVQSLV
  LGAPRYQHIGLVAMFRQNTGMWESNANVKGTQIGAYFGASLCSVDVDSNGSTDLVLIGAP
  HYYEQTRGGQVSVCPLPRGRARWQCDAVLYGEQGQPWGRFGAALTVLGDVNGDKLTDVAI
  GAPGEEDNRGAVYLFHGTSGSGISPSHSQRIAGSKLSPRLQYFGQSLSGGQDLTMDGLVD
  LTVGAQGHVLLLRSQPVLRVKAIMEFNPREVARNVFECNDQVVKGKEAGEVRVCLHVQKS
  TRDRLREGQIQSVVTYDLALDSGRPHSRAVFNETKNSTRRQTQVLGLTQTCETLKLQLPN
  CIEDPVSPIVLRLNFSLVGTPLSAFGNLRPVLAEDAQRLFTALFPFEKNCGNDNICQDDL
  SITFSFMSLDCLVVGGPREFNVTVTVRNDGEDSYRTQVTFFFPLDLSYRKVSTLQNQRSQ
  RSWRLACESASSTEVSGALKSTSCSINHPIFPENSEVTFNITFDVDSKASLGNKLLLKAN
  VTSENNMPRTNKTEFQLELPVKYAVYMVVTSHGVSTKYLNFTASENTSRVMQHQYQVSNL
  GQRSLPISLVFLVPVRLNQTVIWDRPQVTFSENLSSTCHTKERLPSHSDFLAELRKAPVV
  NCSIAVCQRIQCDIPFFGIQEEFNATLKGNLSFDWYIKTSHNHLLIVSTAEILFNDSVFT
  LLPGQGAFVRSQTETKVEPFEVPNPLPLIVGSSVGGLLLLALITAALYKLGFFKRQYKDM
  MSEGGPPGAEPQ
• Function: 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. 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.
• KEGG Pathway:
  Rap1 signaling 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)
  Transcriptional 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 DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GB1275	DMCT9NG	Pancreatic cancer	2C10	Phase 1/2	[2]

References

• [1] Biomarkers of eosinophil involvement in allergic and eosinophilic diseases: review of phenotypic and serum markers including a novel assay to quantify levels of soluble Siglec-8. J Immunol Methods. 2012 Sep 28;383(1-2):39-46.
• [2] National Cancer Institute Drug Dictionary (drug name GB1275).