Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLU8GU8)

• DOT Name: Protein AMBP (AMBP)
• Synonyms: Protein HC
• Gene Name: AMBP
• Related Disease:
  Acute kidney injury
  Acute pyelonephritis
  Advanced cancer
  Bacteremia
  Bladder cancer
  Cardiac failure
  Cardiovascular disease
  Clear cell renal carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Epithelial ovarian cancer
  Glioma
  Haemophilia A
  Hemophilia
  Hepatitis B virus infection
  Hepatitis E virus infection
  Major depressive disorder
  Metastatic malignant neoplasm
  Neoplasm
  Nephropathy
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Prostate neoplasm
  Prostatitis
  Renal cell carcinoma
  Schizophrenia
  Transitional cell carcinoma
  Tuberculosis
  Type-1/2 diabetes
  Vesicoureteral reflux
  Breast cancer
  Breast carcinoma
  High blood pressure
  Mood disorder
  Urinary tract infection
  Pneumonia
  Nephrolithiasis, calcium oxalate
  Squamous cell carcinoma
  Stroke
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: AMBP_HUMAN
• PDB ID: 1BIK; 3QKG; 4ES7; 4U30; 6EJ7; 6EJ8; 6EJ9; 6EJA; 6EJB; 6EJC; 6EJD
• EC Number: 1.6.2.-
• Pfam ID: PF00014 ; PF00061
• Sequence:
  MRSLGALLLLLSACLAVSAGPVPTPPDNIQVQENFNISRIYGKWYNLAIGSTCPWLKKIM
  DRMTVSTLVLGEGATEAEISMTSTRWRKGVCEETSGAYEKTDTDGKFLYHKSKWNITMES
  YVVHTNYDEYAIFLTKKFSRHHGPTITAKLYGRAPQLRETLLQDFRVVAQGVGIPEDSIF
  TMADRGECVPGEQEPEPILIPRVRRAVLPQEEEGSGGGQLVTEVTKKEDSCQLGYSAGPC
  MGMTSRYFYNGTSMACETFQYGGCMGNGNNFVTEKECLQTCRTVAACNLPIVRGPCRAFI
  QLWAFDAVKGKCVLFPYGGCQGNGNKFYSEKECREYCGVPGDGDEELLRFSN
• Function: [Alpha-1-microglobulin]: Antioxidant and tissue repair protein with reductase, heme-binding and radical-scavenging activities. Removes and protects against harmful oxidants and repairs macromolecules in intravascular and extravascular spaces and in intracellular compartments. Intravascularly, plays a regulatory role in red cell homeostasis by preventing heme- and reactive oxygen species-induced cell damage. Binds and degrades free heme to protect fetal and adult red blood cells from hemolysis. Reduces extracellular methemoglobin, a Fe3+ (ferric) form of hemoglobin that cannot bind oxygen, back to the Fe2+ (ferrous) form deoxyhemoglobin, which has oxygen-carrying potential. Upon acute inflammation, inhibits oxidation of low-density lipoprotein particles by MPO and limits vascular damage. Extravascularly, protects from oxidation products formed on extracellular matrix structures and cell membranes. Catalyzes the reduction of carbonyl groups on oxidized collagen fibers and preserves cellular and extracellular matrix ultrastructures. Importantly, counteracts the oxidative damage at blood-placenta interface, preventing leakage of free fetal hemoglobin into the maternal circulation. Intracellularly, has a role in maintaining mitochondrial redox homeostasis. Bound to complex I of the respiratory chain of mitochondria, may scavenge free radicals and preserve mitochondrial ATP synthesis. Protects renal tubule epithelial cells from heme-induced oxidative damage to mitochondria. Reduces cytochrome c from Fe3+ (ferric) to the Fe2+ (ferrous) state through formation of superoxide anion radicals in the presence of ascorbate or NADH/NADPH electron donor cofactors, ascorbate being the preferred cofactor. Has a chaperone role in facilitating the correct folding of bikunin in the endoplasmic reticulum compartment; [Inter-alpha-trypsin inhibitor light chain]: Kunitz-type serine protease inhibitor and structural component of extracellular matrix with a role in extracellular space remodeling and cell adhesion. Among others, has antiprotease activity toward kallikrein, a protease involved in airway inflammation; inhibits GZMK/granzyme, a granule-stored serine protease involved in NK and T cell cytotoxic responses; and inhibits PLG/plasmin, a protease required for activation of matrix metalloproteinases. As part of I-alpha-I complex, provides for the heavy chains to be transferred from I-alpha-I complex to hyaluronan in the presence of TNFAIP6, in a dynamic process that releases free bikunin and remodels extracellular matrix proteoglycan structures. Free bikunin, but not its heavy chain-bound form, acts as potent protease inhibitor in airway secretions. Part of hyaluronan-rich extracellular matrix that surrounds oocyte during cumulus oophorus expansion, an indispensable process for proper ovulation. Also inhibits calcium oxalate crystallization ; [Trypstatin]: Kunitz-type serine protease inhibitor. Has high catalytic efficiency for F10/blood coagulation factor Xa and may act as an anticoagulant by inhibiting prothrombin activation. Inhibits trypsin and mast cell CMA1/chymase and tryptase proteases.
• Tissue Specificity: .Expressed by the liver and secreted in plasma. Occurs in many physiological fluids including plasma, urine, and cerebrospinal fluid . Expressed in epidermal keratinocytes, in dermis and epidermal-dermal junction (at protein level) . Expressed in red blood cells (at protein level) . Expressed in placenta .; [Inter-alpha-trypsin inhibitor light chain]: Detected in placenta (at protein level) . Detected in cerebrospinal fluid, plasma and urine (at protein level) . Expressed in airway epithelium and submucosal gland (at protein level). Colocalizes with TNFAIP6 at the ciliary border. Present in bronchoalveolar lavage fluid (at protein level).
• Reactome Pathway: Scavenging of heme from plasma (R-HSA-2168880)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute kidney injury	DISXZG0T	Strong	Therapeutic	[1]
Acute pyelonephritis	DISLG5PR	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Bacteremia	DIS6N9RZ	Strong	Genetic Variation	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[12]
Hemophilia	DIS1S8P6	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Hepatitis E virus infection	DIS0TXIR	Strong	Biomarker	[14]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Nephropathy	DISXWP4P	Strong	Altered Expression	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[10]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[10]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[19]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[20]
Prostatitis	DISL8OGN	Strong	Biomarker	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Schizophrenia	DISSRV2N	Strong	Biomarker	[22]
Transitional cell carcinoma	DISWVVDR	Strong	Therapeutic	[23]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[24]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[25]
Vesicoureteral reflux	DISUL6SA	Strong	Genetic Variation	[26]
Breast cancer	DIS7DPX1	moderate	Biomarker	[27]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[27]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[28]
Mood disorder	DISLVMWO	moderate	Biomarker	[29]
Urinary tract infection	DISMT6UV	moderate	Biomarker	[30]
Pneumonia	DIS8EF3M	Disputed	Genetic Variation	[31]
Nephrolithiasis, calcium oxalate	DIS5J79C	Limited	Biomarker	[32]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[33]
Stroke	DISX6UHX	Limited	Biomarker	[34]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[35]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein AMBP (AMBP).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein AMBP (AMBP).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein AMBP (AMBP).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein AMBP (AMBP).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein AMBP (AMBP).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein AMBP (AMBP).	[42]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Protein AMBP (AMBP).	[43]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Protein AMBP (AMBP).	[44]
Benazepril	DMH1M9B	Approved	Benazepril decreases the expression of Protein AMBP (AMBP).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein AMBP (AMBP).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein AMBP (AMBP).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein AMBP (AMBP).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein AMBP (AMBP).	[49]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin decreases the expression of Protein AMBP (AMBP).	[45]
Heme	DMGC287	Investigative	Heme increases the expression of Protein AMBP (AMBP).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the binding of Protein AMBP (AMBP).	[38]
1-anilinonaphthalene-8-sulfonic acid	DMNGY0E	Investigative	1-anilinonaphthalene-8-sulfonic acid affects the binding of Protein AMBP (AMBP).	[38]

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