Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNS69WO)

• DOT Name: Integrin alpha-D (ITGAD)
• Synonyms: ADB2; CD11 antigen-like family member D; Leukointegrin alpha D; CD antigen CD11d
• Gene Name: ITGAD
• Related Disease:
  Cone-rod dystrophy 2
  Arteriosclerosis
  Atherosclerosis
  Obesity
• UniProt ID: ITAD_HUMAN
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF00357 ; PF21520 ; PF00092
• Sequence:
  MTFGTVLLLSVLASYHGFNLDVEEPTIFQEDAGGFGQSVVQFGGSRLVVGAPLEVVAANQ
  TGRLYDCAAATGMCQPIPLHIRPEAVNMSLGLTLAASTNGSRLLACGPTLHRVCGENSYS
  KGSCLLLGSRWEIIQTVPDATPECPHQEMDIVFLIDGSGSIDQNDFNQMKGFVQAVMGQF
  EGTDTLFALMQYSNLLKIHFTFTQFRTSPSQQSLVDPIVQLKGLTFTATGILTVVTQLFH
  HKNGARKSAKKILIVITDGQKYKDPLEYSDVIPQAEKAGIIRYAIGVGHAFQGPTARQEL
  NTISSAPPQDHVFKVDNFAALGSIQKQLQEKIYAVEGTQSRASSSFQHEMSQEGFSTALT
  MDGLFLGAVGSFSWSGGAFLYPPNMSPTFINMSQENVDMRDSYLGYSTELALWKGVQNLV
  LGAPRYQHTGKAVIFTQVSRQWRKKAEVTGTQIGSYFGASLCSVDVDSDGSTDLILIGAP
  HYYEQTRGGQVSVCPLPRGRVQWQCDAVLRGEQGHPWGRFGAALTVLGDVNEDKLIDVAI
  GAPGEQENRGAVYLFHGASESGISPSHSQRIASSQLSPRLQYFGQALSGGQDLTQDGLMD
  LAVGARGQVLLLRSLPVLKVGVAMRFSPVEVAKAVYRCWEEKPSALEAGDATVCLTIQKS
  SLDQLGDIQSSVRFDLALDPGRLTSRAIFNETKNPTLTRRKTLGLGIHCETLKLLLPDCV
  EDVVSPIILHLNFSLVREPIPSPQNLRPVLAVGSQDLFTASLPFEKNCGQDGLCEGDLGV
  TLSFSGLQTLTVGSSLELNVIVTVWNAGEDSYGTVVSLYYPAGLSHRRVSGAQKQPHQSA
  LRLACETVPTEDEGLRSSRCSVNHPIFHEGSNGTFIVTFDVSYKATLGDRMLMRASASSE
  NNKASSSKATFQLELPVKYAVYTMISRQEESTKYFNFATSDEKKMKEAEHRYRVNNLSQR
  DLAISINFWVPVLLNGVAVWDVVMEAPSQSLPCVSERKPPQHSDFLTQISRSPMLDCSIA
  DCLQFRCDVPSFSVQEELDFTLKGNLSFGWVRETLQKKVLVVSVAEITFDTSVYSQLPGQ
  EAFMRAQMEMVLEEDEVYNAIPIIMGSSVGALLLLALITATLYKLGFFKRHYKEMLEDKP
  EDTATFSGDDFSCVAPNVPLS
• Function: Integrin alpha-D/beta-2 is a receptor for ICAM3 and VCAM1. May play a role in the atherosclerotic process such as clearing lipoproteins from plaques and in phagocytosis of blood-borne pathogens, particulate matter, and senescent erythrocytes from the blood.
• Tissue Specificity: Expressed moderately on myelomonocytic cell lines and subsets of peripheral blood leukocytes and strongly on tissue-specialized cells, including macrophages foam cells within atherosclerotic plaques, and on splenic red pulp macrophages.
• KEGG Pathway: Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway: Integrin cell surface interactions (R-HSA-216083)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy 2	DISX2RWY	Definitive	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Integrin alpha-D (ITGAD).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Integrin alpha-D (ITGAD).	[5]

References

• [1] The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.Exp Neurol. 2017 Sep;295:125-134. doi: 10.1016/j.expneurol.2017.06.002. Epub 2017 Jun 3.
• [2] The Upregulation of Integrin (D)(2) (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.J Immunol. 2017 Jun 15;198(12):4855-4867. doi: 10.4049/jimmunol.1602175. Epub 2017 May 12.
• [3] Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obese rodents and women.J Nutr. 2011 Jun;141(6):1172-80. doi: 10.3945/jn.110.127068. Epub 2011 Apr 20.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.