Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM8JE4Y)

• DOT Name: Ceruloplasmin (CP)
• Synonyms: Cuproxidase ceruloplasmin; EC 1.16.3.4; Ferroxidase ceruloplasmin; EC 1.16.3.1
• Gene Name: CP
• Related Disease:
  Aceruloplasminemia
  Hyperthyroidism
  Multiple sclerosis
  Acute kidney injury
  Acute myelogenous leukaemia
  Alzheimer disease
  Autism
  Breast cancer
  Breast carcinoma
  Cardiac disease
  Colonic neoplasm
  Congestive heart failure
  Dementia
  Hemolytic anemia
  Hepatocellular carcinoma
  Hypothyroidism
  Iron metabolism disease
  Liver cirrhosis
  Menkes disease
  Movement disorder
  Palmoplantar pustulosis
  Pre-eclampsia
  Psoriasis
  Retinal degeneration
  Rheumatoid arthritis
  Schizophrenia
  Sensory ataxia
  Thyroid tumor
  Type-1 diabetes
  Anemia
  Hereditary hemochromatosis
  Lupus nephritis
  Melanoma
  Neurodegenerative disease
  Age-related macular degeneration
  Arteriosclerosis
  Atherosclerosis
  Brain disease
  Cardiovascular disease
  Colon cancer
  Dystonia
  Hemochromatosis
  Ischemia
  Neoplasm
  Nervous system disease
  Type-1/2 diabetes
• UniProt ID: CERU_HUMAN
• PDB ID: 1KCW; 2J5W; 4EJX; 4ENZ
• EC Number: 1.16.3.1; 1.16.3.4
• Pfam ID: PF00394 ; PF07731 ; PF07732
• Sequence:
  MKILILGIFLFLCSTPAWAKEKHYYIGIIETTWDYASDHGEKKLISVDTEHSNIYLQNGP
  DRIGRLYKKALYLQYTDETFRTTIEKPVWLGFLGPIIKAETGDKVYVHLKNLASRPYTFH
  SHGITYYKEHEGAIYPDNTTDFQRADDKVYPGEQYTYMLLATEEQSPGEGDGNCVTRIYH
  SHIDAPKDIASGLIGPLIICKKDSLDKEKEKHIDREFVVMFSVVDENFSWYLEDNIKTYC
  SEPEKVDKDNEDFQESNRMYSVNGYTFGSLPGLSMCAEDRVKWYLFGMGNEVDVHAAFFH
  GQALTNKNYRIDTINLFPATLFDAYMVAQNPGEWMLSCQNLNHLKAGLQAFFQVQECNKS
  SSKDNIRGKHVRHYYIAAEEIIWNYAPSGIDIFTKENLTAPGSDSAVFFEQGTTRIGGSY
  KKLVYREYTDASFTNRKERGPEEEHLGILGPVIWAEVGDTIRVTFHNKGAYPLSIEPIGV
  RFNKNNEGTYYSPNYNPQSRSVPPSASHVAPTETFTYEWTVPKEVGPTNADPVCLAKMYY
  SAVEPTKDIFTGLIGPMKICKKGSLHANGRQKDVDKEFYLFPTVFDENESLLLEDNIRMF
  TTAPDQVDKEDEDFQESNKMHSMNGFMYGNQPGLTMCKGDSVVWYLFSAGNEADVHGIYF
  SGNTYLWRGERRDTANLFPQTSLTLHMWPDTEGTFNVECLTTDHYTGGMKQKYTVNQCRR
  QSEDSTFYLGERTYYIAAVEVEWDYSPQREWEKELHHLQEQNVSNAFLDKGEFYIGSKYK
  KVVYRQYTDSTFRVPVERKAEEEHLGILGPQLHADVGDKVKIIFKNMATRPYSIHAHGVQ
  TESSTVTPTLPGETLTYVWKIPERSGAGTEDSACIPWAYYSTVDQVKDLYSGLIGPLIVC
  RRPYLKVFNPRRKLEFALLFLVFDENESWYLDDNIKTYSDHPEKVNKDDEEFIESNKMHA
  INGRMFGNLQGLTMHVGDEVNWYLMGMGNEIDLHTVHFHGHSFQYKHRGVYSSDVFDIFP
  GTYQTLEMFPRTPGIWLLHCHVTDHIHAGMETTYTVLQNEDTKSG
• Function: Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Copper ions provide a large number of enzymatic activites. Oxidizes highly toxic ferrous ions to the ferric state for further incorporation onto apo-transferrins, catalyzes Cu(+) oxidation and promotes the oxidation of biogenic amines such as norepinephrin and serotonin. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. Has glutathione peroxidase-like activity, can remove both hydrogen peroxide and lipid hydroperoxide in the presence of thiols. Also shows NO-oxidase and NO2 synthase activities that determine endocrine NO homeostasis.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Ferroptosis (hsa04216)
• Reactome Pathway:
  Metal ion SLC transporters (R-HSA-425410)
  Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages) (R-HSA-5619049)
  Defective CP causes aceruloplasminemia (ACERULOP) (R-HSA-5619060)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Iron uptake and transport (R-HSA-917937)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
• BioCyc Pathway: MetaCyc:HS00590-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aceruloplasminemia	DISDVY3R	Definitive	Autosomal recessive	[1]
Hyperthyroidism	DISX87ZH	Definitive	Biomarker	[2]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[3]
Acute kidney injury	DISXZG0T	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Autism	DISV4V1Z	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Cardiac disease	DISVO1I5	Strong	Biomarker	[9]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[11]
Dementia	DISXL1WY	Strong	Biomarker	[12]
Hemolytic anemia	DIS803XQ	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[15]
Iron metabolism disease	DISWDM9J	Strong	Biomarker	[16]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[17]
Menkes disease	DISJJV50	Strong	Biomarker	[18]
Movement disorder	DISOJJ2D	Strong	Altered Expression	[19]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[20]
Pre-eclampsia	DISY7Q29	Strong	Biomarker	[21]
Psoriasis	DIS59VMN	Strong	Biomarker	[20]
Retinal degeneration	DISM1JHQ	Strong	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[23]
Schizophrenia	DISSRV2N	Strong	Biomarker	[24]
Sensory ataxia	DISSMCYQ	Strong	Biomarker	[22]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[25]
Type-1 diabetes	DIS7HLUB	Strong	Altered Expression	[26]
Anemia	DISTVL0C	moderate	Altered Expression	[19]
Hereditary hemochromatosis	DISVG5MT	moderate	Biomarker	[27]
Lupus nephritis	DISCVGPZ	moderate	Altered Expression	[28]
Melanoma	DIS1RRCY	moderate	Biomarker	[10]
Neurodegenerative disease	DISM20FF	moderate	Therapeutic	[29]
Age-related macular degeneration	DIS0XS2C	Limited	Biomarker	[30]
Arteriosclerosis	DISK5QGC	Limited	Genetic Variation	[31]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[31]
Brain disease	DIS6ZC3X	Limited	Biomarker	[32]
Cardiovascular disease	DIS2IQDX	Limited	Biomarker	[33]
Colon cancer	DISVC52G	Limited	Biomarker	[34]
Dystonia	DISJLFGW	Limited	Genetic Variation	[35]
Hemochromatosis	DISAPY0H	Limited	Biomarker	[36]
Ischemia	DIS5XOOY	Limited	Biomarker	[37]
Neoplasm	DISZKGEW	Limited	Biomarker	[34]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[38]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Ceruloplasmin (CP) affects the abundance of 4-hydroxy-2-nonenal.	[22]

24 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 Ceruloplasmin (CP).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ceruloplasmin (CP).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ceruloplasmin (CP).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ceruloplasmin (CP).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ceruloplasmin (CP).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ceruloplasmin (CP).	[44]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ceruloplasmin (CP).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ceruloplasmin (CP).	[46]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ceruloplasmin (CP).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ceruloplasmin (CP).	[48]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Ceruloplasmin (CP).	[49]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ceruloplasmin (CP).	[50]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ceruloplasmin (CP).	[51]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ceruloplasmin (CP).	[52]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Ceruloplasmin (CP).	[53]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Ceruloplasmin (CP).	[54]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Ceruloplasmin (CP).	[47]
Clofibrate	DMPC1J7	Approved	Clofibrate decreases the expression of Ceruloplasmin (CP).	[56]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ceruloplasmin (CP).	[57]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Ceruloplasmin (CP).	[62]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Ceruloplasmin (CP).	[63]
Uric acid	DMA1MKT	Investigative	Uric acid affects the activity of Ceruloplasmin (CP).	[64]
Pyrrolidine dithiocarbamate	DM5ZAS6	Investigative	Pyrrolidine dithiocarbamate increases the expression of Ceruloplasmin (CP).	[65]
methylglyoxal	DMRC3OZ	Investigative	methylglyoxal decreases the activity of Ceruloplasmin (CP).	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the phosphorylation of Ceruloplasmin (CP).	[55]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ceruloplasmin (CP).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ceruloplasmin (CP).	[61]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the secretion of Ceruloplasmin (CP).	[58]
AMG 386	DMQJXL4	Phase 3	AMG 386 affects the binding of Ceruloplasmin (CP).	[59]

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