Details of Drug Off-Target (DOT)

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

• DOT Name: Integrin alpha-X (ITGAX)
• Synonyms: CD11 antigen-like family member C; Leu M5; Leukocyte adhesion glycoprotein p150,95 alpha chain; Leukocyte adhesion receptor p150,95; CD antigen CD11c
• Gene Name: ITGAX
• Related Disease:
  Colitis
  Acute myelogenous leukaemia
  Alzheimer disease
  Asthma
  Autoimmune disease
  Behcet disease
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Dermatitis
  Diphtheria
  Gastric cancer
  Hairy cell leukaemia
  Lung cancer
  Lung carcinoma
  MALT lymphoma
  Melanoma
  Multiple sclerosis
  Nasal polyp
  Nervous system inflammation
  Non-insulin dependent diabetes
  Obesity
  Pneumonia
  Pneumonitis
  Polycystic ovarian syndrome
  Promyelocytic leukaemia
  Psoriasis
  Pulmonary emphysema
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Stomach cancer
  Systemic lupus erythematosus
  Tuberculosis
  Arteriosclerosis
  Atherosclerosis
  IgA nephropathy
  Squamous cell carcinoma
  Type-1/2 diabetes
  Abdominal aortic aneurysm
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Crohn disease
  Glioma
  Hepatitis C virus infection
  Irritable bowel syndrome
  Malaria
  Prune belly syndrome
• UniProt ID: ITAX_HUMAN
• PDB ID: 1N3Y; 2LUV; 3K6S; 3K71; 3K72; 4NEH; 4NEN; 5ES4
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF00357 ; PF21520 ; PF00092
• Sequence:
  MTRTRAALLLFTALATSLGFNLDTEELTAFRVDSAGFGDSVVQYANSWVVVGAPQKITAA
  NQTGGLYQCGYSTGACEPIGLQVPPEAVNMSLGLSLASTTSPSQLLACGPTVHHECGRNM
  YLTGLCFLLGPTQLTQRLPVSRQECPRQEQDIVFLIDGSGSISSRNFATMMNFVRAVISQ
  FQRPSTQFSLMQFSNKFQTHFTFEEFRRSSNPLSLLASVHQLQGFTYTATAIQNVVHRLF
  HASYGARRDAAKILIVITDGKKEGDSLDYKDVIPMADAAGIIRYAIGVGLAFQNRNSWKE
  LNDIASKPSQEHIFKVEDFDALKDIQNQLKEKIFAIEGTETTSSSSFELEMAQEGFSAVF
  TPDGPVLGAVGSFTWSGGAFLYPPNMSPTFINMSQENVDMRDSYLGYSTELALWKGVQSL
  VLGAPRYQHTGKAVIFTQVSRQWRMKAEVTGTQIGSYFGASLCSVDVDSDGSTDLVLIGA
  PHYYEQTRGGQVSVCPLPRGWRRWWCDAVLYGEQGHPWGRFGAALTVLGDVNGDKLTDVV
  IGAPGEEENRGAVYLFHGVLGPSISPSHSQRIAGSQLSSRLQYFGQALSGGQDLTQDGLV
  DLAVGARGQVLLLRTRPVLWVGVSMQFIPAEIPRSAFECREQVVSEQTLVQSNICLYIDK
  RSKNLLGSRDLQSSVTLDLALDPGRLSPRATFQETKNRSLSRVRVLGLKAHCENFNLLLP
  SCVEDSVTPITLRLNFTLVGKPLLAFRNLRPMLAADAQRYFTASLPFEKNCGADHICQDN
  LGISFSFPGLKSLLVGSNLELNAEVMVWNDGEDSYGTTITFSHPAGLSYRYVAEGQKQGQ
  LRSLHLTCDSAPVGSQGTWSTSCRINHLIFRGGAQITFLATFDVSPKAVLGDRLLLTANV
  SSENNTPRTSKTTFQLELPVKYAVYTVVSSHEQFTKYLNFSESEEKESHVAMHRYQVNNL
  GQRDLPVSINFWVPVELNQEAVWMDVEVSHPQNPSLRCSSEKIAPPASDFLAHIQKNPVL
  DCSIAGCLRFRCDVPSFSVQEELDFTLKGNLSFGWVRQILQKKVSVVSVAEITFDTSVYS
  QLPGQEAFMRAQTTTVLEKYKVHNPTPLIVGSSIGGLLLLALITAVLYKVGFFKRQYKEM
  MEEANGQIAPENGTQTPSPPSEK
• Function: Integrin alpha-X/beta-2 is a receptor for fibrinogen. It recognizes the sequence G-P-R in fibrinogen. It mediates cell-cell interaction during inflammatory responses. It is especially important in monocyte adhesion and chemotaxis.
• Tissue Specificity: Predominantly expressed in monocytes and granulocytes.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Regulation of actin cytoskeleton (hsa04810)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  ECM proteoglycans (R-HSA-3000178)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Neutrophil degranulation (R-HSA-6798695)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Altered Expression	[4]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[5]
Behcet disease	DISSYMBS	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Dermatitis	DISY5SZC	Strong	Biomarker	[10]
Diphtheria	DISZWM55	Strong	Altered Expression	[11]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Hairy cell leukaemia	DISTD2E5	Strong	Altered Expression	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
MALT lymphoma	DIS1AVVE	Strong	Altered Expression	[15]
Melanoma	DIS1RRCY	Strong	Altered Expression	[16]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[17]
Nasal polyp	DISLP3XE	Strong	Biomarker	[18]
Nervous system inflammation	DISB3X5A	Strong	Altered Expression	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[20]
Obesity	DIS47Y1K	Strong	Altered Expression	[21]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[22]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[22]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[23]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[24]
Psoriasis	DIS59VMN	Strong	Biomarker	[25]
Pulmonary emphysema	DIS5M7HZ	Strong	Biomarker	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[27]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[13]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[12]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[28]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[29]
Arteriosclerosis	DISK5QGC	moderate	Biomarker	[30]
Atherosclerosis	DISMN9J3	moderate	Biomarker	[30]
IgA nephropathy	DISZ8MTK	moderate	Genetic Variation	[31]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[32]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[33]
Abdominal aortic aneurysm	DISD06OF	Limited	Biomarker	[34]
B-cell lymphoma	DISIH1YQ	Limited	Altered Expression	[35]
Breast cancer	DIS7DPX1	Limited	Biomarker	[36]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[36]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[37]
Glioma	DIS5RPEH	Limited	Biomarker	[38]
Hepatitis C virus infection	DISQ0M8R	Limited	Altered Expression	[39]
Irritable bowel syndrome	DIS27206	Limited	Altered Expression	[40]
Malaria	DISQ9Y50	Limited	Biomarker	[41]
Prune belly syndrome	DISBIBMN	Limited	Biomarker	[42]

16 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-X (ITGAX).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Integrin alpha-X (ITGAX).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Integrin alpha-X (ITGAX).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Integrin alpha-X (ITGAX).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Integrin alpha-X (ITGAX).	[44]
Marinol	DM70IK5	Approved	Marinol increases the expression of Integrin alpha-X (ITGAX).	[47]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Integrin alpha-X (ITGAX).	[48]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Integrin alpha-X (ITGAX).	[49]
Cimetidine	DMH61ZB	Approved	Cimetidine decreases the expression of Integrin alpha-X (ITGAX).	[50]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin decreases the expression of Integrin alpha-X (ITGAX).	[51]
Bryostatin-1	DM1JOXY	Phase 2	Bryostatin-1 increases the expression of Integrin alpha-X (ITGAX).	[52]
Tesmilifene	DMPB36I	Discontinued in Phase 2	Tesmilifene decreases the expression of Integrin alpha-X (ITGAX).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Integrin alpha-X (ITGAX).	[55]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Integrin alpha-X (ITGAX).	[56]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Integrin alpha-X (ITGAX).	[57]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Integrin alpha-X (ITGAX).	[58]

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-X (ITGAX).	[53]

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