Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHMF4YM)

• DOT Name: Complement C2 (C2)
• Synonyms: EC 3.4.21.43; C3/C5 convertase
• Gene Name: C2
• Related Disease:
  Hypothyroidism
  Alzheimer disease
  Astrocytoma
  Autoimmune disease
  Complement component 2 deficiency
  Complement deficiency
  Dermatomyositis
  Graves disease
  Hepatocellular carcinoma
  IgA nephropathy
  Irritant contact dermatitis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lupus
  Multiple sclerosis
  Myasthenia gravis
  Neovascular age-related macular degeneration
  Schizophrenia
  Systemic lupus erythematosus
  Type-1 diabetes
  Type-1/2 diabetes
  Coronary heart disease
  Endometriosis
  Metabolic disorder
  Age-related macular degeneration
  Chronic hepatitis B virus infection
  Juvenile idiopathic arthritis
  Neoplasm
  Rheumatic disorder
  Rheumatoid arthritis
  Schistosomiasis
• UniProt ID: CO2_HUMAN
• PDB ID: 2I6Q; 2I6S; 2ODP; 2ODQ; 3ERB
• EC Number: 3.4.21.43
• Pfam ID: PF00084 ; PF00089 ; PF00092
• Sequence:
  MGPLMVLFCLLFLYPGLADSAPSCPQNVNISGGTFTLSHGWAPGSLLTYSCPQGLYPSPA
  SRLCKSSGQWQTPGATRSLSKAVCKPVRCPAPVSFENGIYTPRLGSYPVGGNVSFECEDG
  FILRGSPVRQCRPNGMWDGETAVCDNGAGHCPNPGISLGAVRTGFRFGHGDKVRYRCSSN
  LVLTGSSERECQGNGVWSGTEPICRQPYSYDFPEDVAPALGTSFSHMLGATNPTQKTKES
  LGRKIQIQRSGHLNLYLLLDCSQSVSENDFLIFKESASLMVDRIFSFEINVSVAIITFAS
  EPKVLMSVLNDNSRDMTEVISSLENANYKDHENGTGTNTYAALNSVYLMMNNQMRLLGME
  TMAWQEIRHAIILLTDGKSNMGGSPKTAVDHIREILNINQKRNDYLDIYAIGVGKLDVDW
  RELNELGSKKDGERHAFILQDTKALHQVFEHMLDVSKLTDTICGVGNMSANASDQERTPW
  HVTIKPKSQETCRGALISDQWVLTAAHCFRDGNDHSLWRVNVGDPKSQWGKEFLIEKAVI
  SPGFDVFAKKNQGILEFYGDDIALLKLAQKVKMSTHARPICLPCTMEANLALRRPQGSTC
  RDHENELLNKQSVPAHFVALNGSKLNINLKMGVEWTSCAEVVSQEKTMFPNLTDVREVVT
  DQFLCSGTQEDESPCKGESGGAVFLERRFRFFQVGLVSWGLYNPCLGSADKNSRKRAPRS
  KVPPPRDFHINLFRMQPWLRQHLGDVLNFLPL
• Function: Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Alcoholic liver disease (hsa04936)
  Pertussis (hsa05133)
  Staphylococcus aureus infection (hsa05150)
  Coro.virus disease - COVID-19 (hsa05171)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Activation of C3 and C5 (R-HSA-174577)
  Regulation of Complement cascade (R-HSA-977606)
  Initial triggering of complement (R-HSA-166663)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypothyroidism	DISR0H6D	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Astrocytoma	DISL3V18	Strong	Altered Expression	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Complement component 2 deficiency	DIS8OWGU	Strong	Autosomal recessive	[5]
Complement deficiency	DISGN469	Strong	Biomarker	[6]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[7]
Graves disease	DISU4KOQ	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[9]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[10]
Irritant contact dermatitis	DIS62JY3	Strong	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Lupus	DISOKJWA	Strong	Biomarker	[14]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[15]
Myasthenia gravis	DISELRCI	Strong	Altered Expression	[16]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[17]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[19]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[20]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[21]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[22]
Endometriosis	DISX1AG8	moderate	Genetic Variation	[23]
Metabolic disorder	DIS71G5H	Disputed	Genetic Variation	[24]
Age-related macular degeneration	DIS0XS2C	Limited	Genetic Variation	[25]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Genetic Variation	[26]
Juvenile idiopathic arthritis	DISQZGBV	Limited	Biomarker	[27]
Neoplasm	DISZKGEW	Limited	Biomarker	[28]
Rheumatic disorder	DIS77ACK	Limited	Biomarker	[27]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[29]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[30]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Sodium lauryl sulfate	DMLJ634	Approved	Complement C2 (C2) affects the response to substance of Sodium lauryl sulfate.	[11]

8 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 C2 (C2).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Complement C2 (C2).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Complement C2 (C2).	[33]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Complement C2 (C2).	[34]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Complement C2 (C2).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Complement C2 (C2).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Complement C2 (C2).	[39]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Complement C2 (C2).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Complement C2 (C2).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Complement C2 (C2).	[37]

References

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