Details of Drug Off-Target (DOT)

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

DOT Name	Ficolin-2 (FCN2)
Synonyms	37 kDa elastin-binding protein; Collagen/fibrinogen domain-containing protein 2; EBP-37; Ficolin-B; Ficolin-beta; Hucolin; L-ficolin; Serum lectin p35
Gene Name	FCN2
Related Disease	Behcet disease ( ) Systemic lupus erythematosus ( ) Advanced cancer ( ) Alzheimer disease ( ) Astrocytoma ( ) Autoimmune disease ( ) Bone osteosarcoma ( ) Crohn disease ( ) Epithelial ovarian cancer ( ) Hepatitis B virus infection ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Immunodeficiency ( ) Inflammatory bowel disease ( ) Influenza ( ) Liver cirrhosis ( ) Lung cancer ( ) Lung carcinoma ( ) Lupus nephritis ( ) Lyme disease ( ) Malignant mesothelioma ( ) Neoplasm ( ) Osteosarcoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Prostate carcinoma ( ) Psoriasis ( ) Rheumatic fever ( ) Rheumatic heart disease ( ) Schistosomiasis ( ) Schizophrenia ( ) Streptococcus infection ( ) Stroke ( ) Tuberculosis ( ) Matthew-Wood syndrome ( ) Neuroblastoma ( ) Pancreatic ductal carcinoma ( ) Intellectual disability ( ) Leishmaniasis ( ) Malaria ( ) Myocardial infarction ( ) Nephritis ( ) Nervous system disease ( ) Pancreatic cancer ( ) Pneumonia ( ) Pulmonary tuberculosis ( ) Systemic sclerosis ( ) Type-1 diabetes ( )
UniProt ID	FCN2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2J0G; 2J0H; 2J0Y; 2J1G; 2J2P; 2J3F; 2J3G; 2J3O; 2J3U; 2J61; 4NYT; 4R9J; 4R9T
Pfam ID	PF01391 ; PF00147
Sequence	MELDRAVGVLGAATLLLSFLGMAWALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPG PKGEAGTNGKRGERGPPGPPGKAGPPGPNGAPGEPQPCLTGPRTCKDLLDRGHFLSGWHT IYLPDCRPLTVLCDMDTDGGGWTVFQRRVDGSVDFYRDWATYKQGFGSRLGEFWLGNDNI HALTAQGTSELRVDLVDFEDNYQFAKYRSFKVADEAEKYNLVLGAFVEGSAGDSLTFHNN QSFSTKDQDNDLNTGNCAVMFQGAWWYKNCHVSNLNGRYLRGTHGSFANGINWKSGKGYN YSYKVSEMKVRPA
Function	May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc-binding lectin. Enhances phagocytosis of S.typhimurium by neutrophils, suggesting an opsonic effect via the collagen region.
Tissue Specificity	Expressed by the liver and secreted in plasma.
Reactome Pathway	Initial triggering of complement (R-HSA-166663 ) Ficolins bind to repetitive carbohydrate structures on the target cell surface (R-HSA-2855086 ) Lectin pathway of complement activation (R-HSA-166662 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Behcet disease	DISSYMBS	Definitive	Altered Expression	[1]
Systemic lupus erythematosus	DISI1SZ7	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Immunodeficiency	DIS093I0	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[12]
Influenza	DIS3PNU3	Strong	Biomarker	[13]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[15]
Lupus nephritis	DISCVGPZ	Strong	Genetic Variation	[2]
Lyme disease	DISO70G5	Strong	Altered Expression	[16]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[19]
Psoriasis	DIS59VMN	Strong	Biomarker	[20]
Rheumatic fever	DISLUF66	Strong	Genetic Variation	[21]
Rheumatic heart disease	DISCI8JQ	Strong	Genetic Variation	[21]
Schistosomiasis	DIS6PD44	Strong	Altered Expression	[22]
Schizophrenia	DISSRV2N	Strong	Biomarker	[23]
Streptococcus infection	DIS04U9T	Strong	Genetic Variation	[21]
Stroke	DISX6UHX	Strong	Biomarker	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Matthew-Wood syndrome	DISA7HR7	moderate	Genetic Variation	[26]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[27]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[26]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[28]
Leishmaniasis	DISABTW7	Limited	Biomarker	[29]
Malaria	DISQ9Y50	Limited	Genetic Variation	[30]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[31]
Nephritis	DISQZQ70	Limited	Biomarker	[32]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[33]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[34]
Pneumonia	DIS8EF3M	Limited	Genetic Variation	[35]
Pulmonary tuberculosis	DIS6FLUM	Limited	Genetic Variation	[36]
Systemic sclerosis	DISF44L6	Limited	Altered Expression	[37]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[38]
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⏷ Show the Full List of 48 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ficolin-2 (FCN2).	[39]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ficolin-2 (FCN2).	[40]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ficolin-2 (FCN2).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ficolin-2 (FCN2).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ficolin-2 (FCN2).	[43]
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References

1	Increased expression of interleukin-23 p19 mRNA in erythema nodosum-like lesions of Behet's disease.Br J Dermatol. 2008 Mar;158(3):505-11. doi: 10.1111/j.1365-2133.2007.08403.x. Epub 2008 Jan 17.
2	Association of ficolin-2 gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multicenter study.Lupus. 2019 Jul;28(8):995-1002. doi: 10.1177/0961203319856089. Epub 2019 Jun 10.
3	Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours.Cancer Immunol Immunother. 2013 Aug;62(8):1411-9. doi: 10.1007/s00262-013-1445-3. Epub 2013 Jun 7.
4	p35 Hemizygous Deletion in 5xFAD Mice Increases A Plaque Load in Males but Not in Females.Neuroscience. 2019 Oct 1;417:45-56. doi: 10.1016/j.neuroscience.2019.08.017. Epub 2019 Aug 14.
5	Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock.J Cell Sci. 2001 Mar;114(Pt 6):1145-53. doi: 10.1242/jcs.114.6.1145.
6	Low ficolin-2 levels in common variable immunodeficiency patients with bronchiectasis.Clin Exp Immunol. 2015 Feb;179(2):256-64. doi: 10.1111/cei.12459.
7	p35 is required for CDK5 activation in cellular senescence.J Biol Chem. 2010 May 7;285(19):14671-80. doi: 10.1074/jbc.M109.066118. Epub 2010 Feb 24.
8	Specific seroreactivity of Crohn's disease patients against p35 and p36 antigens of M. avium subsp. paratuberculosis.Vet Microbiol. 2000 Dec 20;77(3-4):497-504. doi: 10.1016/s0378-1135(00)00334-5.
9	Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients.PLoS One. 2011;6(11):e28113. doi: 10.1371/journal.pone.0028113. Epub 2011 Nov 22.
10	Elevated serum activity of MBL and ficolin-2 as biomarkers for progression to hepatocellular carcinoma in chronic HCV infection.Virology. 2019 Apr;530:99-106. doi: 10.1016/j.virol.2019.02.002. Epub 2019 Feb 12.
11	Ficolin-2 binds to HIV-1 gp120 and blocks viral infection.Virol Sin. 2016 Oct;31(5):406-414. doi: 10.1007/s12250-016-3808-3. Epub 2016 Aug 29.
12	Ficolin-A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis.Immunology. 2017 Aug;151(4):433-450. doi: 10.1111/imm.12741. Epub 2017 May 15.
13	L-ficolin binds to the glycoproteins hemagglutinin and neuraminidase and inhibits influenza A virus infection both in vitro and in vivo.J Innate Immun. 2012;4(3):312-24. doi: 10.1159/000335670. Epub 2012 Mar 2.
14	Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections.Liver Int. 2017 Jul;37(7):1023-1031. doi: 10.1111/liv.13368. Epub 2017 Feb 28.
15	Achaete-scute homologue-1 (ASH1) stimulates migration of lung cancer cells through Cdk5/p35 pathway.Mol Biol Cell. 2012 Aug;23(15):2856-66. doi: 10.1091/mbc.E10-12-1010. Epub 2012 Jun 13.
16	Differential expression of Borrelia burgdorferi genes during erythema migrans and Lyme arthritis.J Infect Dis. 1998 Oct;178(4):1198-201. doi: 10.1086/515684.
17	Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool.PLoS One. 2012;7(10):e46091. doi: 10.1371/journal.pone.0046091. Epub 2012 Oct 3.
18	Ficolin-2 triggers antitumor effect by activating macrophages and CD8(+) T cells.Clin Immunol. 2017 Oct;183:145-157. doi: 10.1016/j.clim.2017.08.012. Epub 2017 Aug 26.
19	Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis.J Biol Chem. 2004 Jul 9;279(28):29302-7. doi: 10.1074/jbc.M403664200. Epub 2004 Apr 30.
20	Clinical Significance of Decreased Interleukin-35 Expression in Patients with Psoriasis.Microbiol Immunol. 2018 May 26. doi: 10.1111/1348-0421.12605. Online ahead of print.
21	MBL2 and FCN2 gene polymorphisms in a cohort of Italian children with rheumatic fever: A case-control study.Semin Arthritis Rheum. 2017 Oct;47(2):264-268. doi: 10.1016/j.semarthrit.2017.04.006. Epub 2017 Apr 27.
22	Mannose-binding lectin and susceptibility to schistosomiasis.J Infect Dis. 2013 Jun 1;207(11):1675-83. doi: 10.1093/infdis/jit081. Epub 2013 Feb 28.
23	Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition.Brain. 2011 Aug;134(Pt 8):2408-21. doi: 10.1093/brain/awr155. Epub 2011 Jul 19.
24	Zinc induces CDK5 activation and neuronal death through CDK5-Tyr15 phosphorylation in ischemic stroke.Cell Death Dis. 2018 Aug 29;9(9):870. doi: 10.1038/s41419-018-0929-7.
25	No Strong Relationship Between Components of the Lectin Pathway of Complement and Susceptibility to Pulmonary Tuberculosis.Inflammation. 2015 Aug;38(4):1731-7. doi: 10.1007/s10753-015-0150-0.
26	Cyclin-dependent kinase 5 is amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras.Clin Cancer Res. 2011 Oct 1;17(19):6140-50. doi: 10.1158/1078-0432.CCR-10-2288. Epub 2011 Aug 8.
27	Induction of cyclin-dependent kinase 5 and its activator p35 through the extracellular-signal-regulated kinase and protein kinase A pathways during retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N-BE(2)C cells.J Neurochem. 2004 Nov;91(3):634-47. doi: 10.1111/j.1471-4159.2004.02770.x.
28	Effects of p35 Mutations Associated with Mental Retardation on the Cellular Function of p35-CDK5.PLoS One. 2015 Oct 15;10(10):e0140821. doi: 10.1371/journal.pone.0140821. eCollection 2015.
29	IL12 p35 and p40 subunit genes administered as pPAL plasmid constructs do not improve protection of pPAL-LACK vaccine against canine leishmaniasis.PLoS One. 2019 Feb 22;14(2):e0212136. doi: 10.1371/journal.pone.0212136. eCollection 2019.
30	Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria.Hum Immunol. 2011 Jan;72(1):74-9. doi: 10.1016/j.humimm.2010.10.003. Epub 2010 Oct 30.
31	Pentraxin 3, ficolin-2 and lectin pathway associated serine protease MASP-3 as early predictors of myocardial infarction - the HUNT2 study.Sci Rep. 2017 Feb 20;7:43045. doi: 10.1038/srep43045.
32	Autoantibodies Targeting Ficolin-2 in Systemic Lupus Erythematosus Patients With Active Nephritis.Arthritis Care Res (Hoboken). 2018 Aug;70(8):1263-1268. doi: 10.1002/acr.23449. Epub 2018 Jun 21.
33	Calpastatin, an endogenous calpain-inhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25.J Neurochem. 2011 May;117(3):504-15. doi: 10.1111/j.1471-4159.2011.07222.x. Epub 2011 Mar 15.
34	Pancreatic cancer-associated inflammation drives dynamic regulation of p35 and Ebi3.Cytokine. 2020 Jan;125:154817. doi: 10.1016/j.cyto.2019.154817. Epub 2019 Aug 28.
35	Mannose-binding lectin and l-ficolin polymorphisms in patients with community-acquired pneumonia caused by intracellular pathogens.Immunology. 2017 May;151(1):81-88. doi: 10.1111/imm.12705. Epub 2017 Jan 24.
36	Association of the FCN2 Gene Single Nucleotide Polymorphisms with Susceptibility to Pulmonary Tuberculosis.PLoS One. 2015 Sep 17;10(9):e0138356. doi: 10.1371/journal.pone.0138356. eCollection 2015.
37	Role of lectin pathway complement proteins and genetic variants in organ damage and disease severity of systemic sclerosis: a cross-sectional study.Arthritis Res Ther. 2019 Mar 18;21(1):76. doi: 10.1186/s13075-019-1859-1.
38	Impaired processing and presentation by MHC class II proteins in human diabetic cells.J Immunol. 2003 Jan 1;170(1):620-7. doi: 10.4049/jimmunol.170.1.620.
39	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
40	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
41	Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
42	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
43	Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.