Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCH5GS0)

• DOT Name: Complement C3 (C3)
• Synonyms: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1
• Gene Name: C3
• Related Disease:
  Atypical hemolytic-uremic syndrome with C3 anomaly
  Complement component 3 deficiency
  C3 glomerulonephritis
• UniProt ID: CO3_HUMAN
• PDB ID: 1C3D ; 1GHQ ; 1W2S ; 2A73 ; 2A74 ; 2GOX ; 2I07 ; 2ICE ; 2ICF ; 2NOJ ; 2QKI ; 2WII ; 2WIN ; 2WY7 ; 2WY8 ; 2XQW ; 2XWB ; 2XWJ ; 3D5R ; 3D5S ; 3G6J ; 3L3O ; 3L5N ; 3NMS ; 3OED ; 3OHX ; 3OXU ; 3RJ3 ; 3T4A ; 4HW5 ; 4HWJ ; 4I6O ; 4M76 ; 4ONT ; 4ZH1 ; 5FO7 ; 5FO8 ; 5FO9 ; 5FOA ; 5FOB ; 5NBQ ; 5O32 ; 5O35 ; 6EHG ; 6RMT ; 6RMU ; 6RUR ; 6RUV ; 6S0B ; 6YO6 ; 7AKK ; 7BAG ; 7NOZ ; 7PI6 ; 7QIV ; 7TV9 ; 7UE9 ; 7ZGK ; 8ENU ; 8EOK ; 8HK2 ; 8I9L
• Pfam ID: PF00207 ; PF07703 ; PF07677 ; PF01821 ; PF21406 ; PF21308 ; PF17790 ; PF01835 ; PF17791 ; PF17789 ; PF01759 ; PF07678
• Sequence:
  MGPTSGPSLLLLLLTHLPLALGSPMYSIITPNILRLESEETMVLEAHDAQGDVPVTVTVH
  DFPGKKLVLSSEKTVLTPATNHMGNVTFTIPANREFKSEKGRNKFVTVQATFGTQVVEKV
  VLVSLQSGYLFIQTDKTIYTPGSTVLYRIFTVNHKLLPVGRTVMVNIENPEGIPVKQDSL
  SSQNQLGVLPLSWDIPELVNMGQWKIRAYYENSPQQVFSTEFEVKEYVLPSFEVIVEPTE
  KFYYIYNEKGLEVTITARFLYGKKVEGTAFVIFGIQDGEQRISLPESLKRIPIEDGSGEV
  VLSRKVLLDGVQNPRAEDLVGKSLYVSATVILHSGSDMVQAERSGIPIVTSPYQIHFTKT
  PKYFKPGMPFDLMVFVTNPDGSPAYRVPVAVQGEDTVQSLTQGDGVAKLSINTHPSQKPL
  SITVRTKKQELSEAEQATRTMQALPYSTVGNSNNYLHLSVLRTELRPGETLNVNFLLRMD
  RAHEAKIRYYTYLIMNKGRLLKAGRQVREPGQDLVVLPLSITTDFIPSFRLVAYYTLIGA
  SGQREVVADSVWVDVKDSCVGSLVVKSGQSEDRQPVPGQQMTLKIEGDHGARVVLVAVDK
  GVFVLNKKNKLTQSKIWDVVEKADIGCTPGSGKDYAGVFSDAGLTFTSSSGQQTAQRAEL
  QCPQPAARRRRSVQLTEKRMDKVGKYPKELRKCCEDGMRENPMRFSCQRRTRFISLGEAC
  KKVFLDCCNYITELRRQHARASHLGLARSNLDEDIIAEENIVSRSEFPESWLWNVEDLKE
  PPKNGISTKLMNIFLKDSITTWEILAVSMSDKKGICVADPFEVTVMQDFFIDLRLPYSVV
  RNEQVEIRAVLYNYRQNQELKVRVELLHNPAFCSLATTKRRHQQTVTIPPKSSLSVPYVI
  VPLKTGLQEVEVKAAVYHHFISDGVRKSLKVVPEGIRMNKTVAVRTLDPERLGREGVQKE
  DIPPADLSDQVPDTESETRILLQGTPVAQMTEDAVDAERLKHLIVTPSGCGEQNMIGMTP
  TVIAVHYLDETEQWEKFGLEKRQGALELIKKGYTQQLAFRQPSSAFAAFVKRAPSTWLTA
  YVVKVFSLAVNLIAIDSQVLCGAVKWLILEKQKPDGVFQEDAPVIHQEMIGGLRNNNEKD
  MALTAFVLISLQEAKDICEEQVNSLPGSITKAGDFLEANYMNLQRSYTVAIAGYALAQMG
  RLKGPLLNKFLTTAKDKNRWEDPGKQLYNVEATSYALLALLQLKDFDFVPPVVRWLNEQR
  YYGGGYGSTQATFMVFQALAQYQKDAPDHQELNLDVSLQLPSRSSKITHRIHWESASLLR
  SEETKENEGFTVTAEGKGQGTLSVVTMYHAKAKDQLTCNKFDLKVTIKPAPETEKRPQDA
  KNTMILEICTRYRGDQDATMSILDISMMTGFAPDTDDLKQLANGVDRYISKYELDKAFSD
  RNTLIIYLDKVSHSEDDCLAFKVHQYFNVELIQPGAVKVYAYYNLEESCTRFYHPEKEDG
  KLNKLCRDELCRCAEENCFIQKSDDKVTLEERLDKACEPGVDYVYKTRLVKVQLSNDFDE
  YIMAIEQTIKSGSDEVQVGQQRTFISPIKCREALKLEEKKHYLMWGLSSDFWGEKPNLSY
  IIGKDTWVEHWPEEDECQDEENQKQCQDLGAFTESMVVFGCPN
• Function: C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.; Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes; [C3-beta-c]: Acts as a chemoattractant for neutrophils in chronic inflammation; [Acylation stimulating protein]: Adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2.
• Tissue Specificity: Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into the plasma during both the fasting and postprandial periods.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Phagosome (hsa04145)
  Complement and coagulation cascades (hsa04610)
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholic liver disease (hsa04936)
  Shigellosis (hsa05131)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Coro.virus disease - COVID-19 (hsa05171)
  Viral carcinogenesis (hsa05203)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Activation of C3 and C5 (R-HSA-174577)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Peptide ligand-binding receptors (R-HSA-375276)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  G alpha (i) signalling events (R-HSA-418594)
  Neutrophil degranulation (R-HSA-6798695)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Regulation of Complement cascade (R-HSA-977606)
  Alternative complement activation (R-HSA-173736)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atypical hemolytic-uremic syndrome with C3 anomaly	DISKM417	Definitive	Autosomal dominant	[1]
Complement component 3 deficiency	DISVCAI0	Definitive	Autosomal recessive	[2]
C3 glomerulonephritis	DIS0KF9P	Moderate	Autosomal dominant	[1]

34 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 Complement C3 (C3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Complement C3 (C3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Complement C3 (C3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Complement C3 (C3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Complement C3 (C3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Complement C3 (C3).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Complement C3 (C3).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Complement C3 (C3).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Complement C3 (C3).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Complement C3 (C3).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Complement C3 (C3).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Complement C3 (C3).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Complement C3 (C3).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Complement C3 (C3).	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Complement C3 (C3).	[9]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Complement C3 (C3).	[17]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Complement C3 (C3).	[18]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Complement C3 (C3).	[19]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Complement C3 (C3).	[20]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Complement C3 (C3).	[21]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Complement C3 (C3).	[20]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Complement C3 (C3).	[22]
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of Complement C3 (C3).	[23]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Complement C3 (C3).	[24]
Danazol	DML8KTN	Approved	Danazol increases the expression of Complement C3 (C3).	[26]
Glyceryl trinitrate	DMF72W3	Phase 4	Glyceryl trinitrate increases the expression of Complement C3 (C3).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Complement C3 (C3).	[29]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Complement C3 (C3).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Complement C3 (C3).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Complement C3 (C3).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Complement C3 (C3).	[34]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Complement C3 (C3).	[35]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Complement C3 (C3).	[36]
9-phenanthrol	DMJFBQ1	Investigative	9-phenanthrol increases the expression of Complement C3 (C3).	[37]

1 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 Complement C3 (C3).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chondroitin sulfate	DM0N19Y	Phase 4	Chondroitin sulfate increases the cleavage of Complement C3 (C3).	[28]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB increases the metabolism of Complement C3 (C3).	[32]

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