Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK6ZHXH)

DOT Name	Ficolin-1 (FCN1)
Synonyms	Collagen/fibrinogen domain-containing protein 1; Ficolin-A; Ficolin-alpha; M-ficolin
Gene Name	FCN1
Related Disease	Immunodeficiency due to MASP-2 deficiency ( ) Cerebral infarction ( ) Chronic fatigue syndrome ( ) Coronary heart disease ( ) Cystic fibrosis ( ) Hyperlipidemia ( ) Inflammatory bowel disease ( ) Leprosy ( ) Liver cirrhosis ( ) Medullary sponge kidney ( ) Neoplasm ( ) Pulmonary disease ( ) Rheumatic fever ( ) Rheumatic heart disease ( ) Subarachnoid hemorrhage ( ) Arthritis ( ) Autoimmune disease ( ) Chronic renal failure ( ) End-stage renal disease ( ) Lupus nephritis ( ) Stroke ( ) Vasculitis ( ) Microscopic polyangiitis ( )
UniProt ID	FCN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2D39; 2JHH; 2JHI; 2JHK; 2JHL; 2JHM; 2WNP
Pfam ID	PF01391 ; PF00147
Sequence	MELSGATMARGLAVLLVLFLHIKNLPAQAADTCPEVKVVGLEGSDKLTILRGCPGLPGAP GPKGEAGVIGERGERGLPGAPGKAGPVGPKGDRGEKGMRGEKGDAGQSQSCATGPRNCKD LLDRGYFLSGWHTIYLPDCRPLTVLCDMDTDGGGWTVFQRRMDGSVDFYRDWAAYKQGFG SQLGEFWLGNDNIHALTAQGSSELRVDLVDFEGNHQFAKYKSFKVADEAEKYKLVLGAFV GGSAGNSLTGHNNNFFSTKDQDNDVSSSNCAEKFQGAWWYADCHASNLNGLYLMGPHESY ANGINWSAAKGYKYSYKVSEMKVRPA
Function	Extracellular lectin functioning as a pattern-recognition receptor in innate immunity. Binds the sugar moieties of pathogen-associated molecular patterns (PAMPs) displayed on microbes and activates the lectin pathway of the complement system. May also activate monocytes through a G protein-coupled receptor, FFAR2, inducing the secretion of interleukin-8/IL-8. Binds preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage.
Tissue Specificity	Peripheral blood leukocytes, monocytes and granulocytes. Also detected in spleen, lung, and thymus, may be due to the presence of tissue macrophages or trapped blood in these tissues. Not detected on lymphocytes.
Reactome Pathway	Initial triggering of complement (R-HSA-166663 ) Ficolins bind to repetitive carbohydrate structures on the target cell surface (R-HSA-2855086 ) Neutrophil degranulation (R-HSA-6798695 ) Lectin pathway of complement activation (R-HSA-166662 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Immunodeficiency due to MASP-2 deficiency	DISVZ6G7	Definitive	Genetic Variation	[1]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[2]
Chronic fatigue syndrome	DIS34WJ5	Strong	Altered Expression	[3]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[5]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[6]
Leprosy	DISAA4UI	Strong	Genetic Variation	[7]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[8]
Medullary sponge kidney	DISA0949	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Pulmonary disease	DIS6060I	Strong	Biomarker	[11]
Rheumatic fever	DISLUF66	Strong	Altered Expression	[12]
Rheumatic heart disease	DISCI8JQ	Strong	Biomarker	[12]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Altered Expression	[13]
Arthritis	DIST1YEL	moderate	Biomarker	[14]
Autoimmune disease	DISORMTM	moderate	Biomarker	[14]
Chronic renal failure	DISGG7K6	moderate	Genetic Variation	[15]
End-stage renal disease	DISXA7GG	moderate	Genetic Variation	[15]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[15]
Stroke	DISX6UHX	moderate	Altered Expression	[16]
Vasculitis	DISQRKDX	moderate	Altered Expression	[14]
Microscopic polyangiitis	DIS74KSO	Limited	Altered Expression	[17]
------------------------------------------------------------------------------------


⏷ Show the Full List of 23 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ficolin-1 (FCN1).	[18]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Ficolin-1 (FCN1).	[19]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ficolin-1 (FCN1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ficolin-1 (FCN1).	[22]
------------------------------------------------------------------------------------

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ficolin-1 (FCN1).	[21]
------------------------------------------------------------------------------------

References

1	Components of the lectin pathway of complement activation in paediatric patients of intensive care units.Immunobiology. 2016 May;221(5):657-69. doi: 10.1016/j.imbio.2016.01.003. Epub 2016 Jan 15.
2	Ficolin-1 Levels in Patients Developing Vasospasm and Cerebral Ischemia After Spontaneous Subarachnoid Hemorrhage.Mol Neurobiol. 2017 Oct;54(8):6572-6580. doi: 10.1007/s12035-016-0180-0. Epub 2016 Oct 12.
3	Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome.Mol Med. 2009 Jan-Feb;15(1-2):34-42. doi: 10.2119/molmed.2008.00098. Epub 2008 Nov 10.
4	NCF2, MYO1F, S1PR4, and FCN1 as potential noninvasive diagnostic biomarkers in patients with obstructive coronary artery: A weighted gene co-expression network analysis.J Cell Biochem. 2019 Oct;120(10):18219-18235. doi: 10.1002/jcb.29128. Epub 2019 Jun 27.
5	Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients.Hum Immunol. 2012 Nov;73(11):1175-83. doi: 10.1016/j.humimm.2012.08.010. Epub 2012 Aug 29.
6	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.
7	Susceptibility to leprosy is associated with M-ficolin polymorphisms.J Clin Immunol. 2013 Jan;33(1):210-9. doi: 10.1007/s10875-012-9770-4. Epub 2012 Sep 1.
8	Prognostic value of lectin pathway molecules and complement proteins in ascitic fluid and blood in patients with liver cirrhosis.Scand J Gastroenterol. 2018 Jan;53(1):64-69. doi: 10.1080/00365521.2017.1386710. Epub 2017 Oct 6.
9	Proteomic Analysis of Urinary Extracellular Vesicles Reveals a Role for the Complement System in Medullary Sponge Kidney Disease.Int J Mol Sci. 2019 Nov 5;20(21):5517. doi: 10.3390/ijms20215517.
10	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.
11	M-ficolin in the neonatal period: Associations with need for mechanical ventilation and mortality in premature infants with necrotising enterocolitis.Mol Immunol. 2009 Aug;46(13):2597-603. doi: 10.1016/j.molimm.2009.05.003. Epub 2009 Jun 18.
12	Sickening or Healing the Heart? The Association of Ficolin-1 and Rheumatic Fever.Front Immunol. 2018 Dec 18;9:3009. doi: 10.3389/fimmu.2018.03009. eCollection 2018.
13	Changes in the Lectin Pathway Following Intracerebral or Spontaneous Subarachnoid Hemorrhage.Mol Neurobiol. 2019 Jan;56(1):78-87. doi: 10.1007/s12035-018-1066-0. Epub 2018 Apr 19.
14	Ficolin-1 is a promising therapeutic target for autoimmune diseases.Int Immunol. 2019 Feb 6;31(1):23-32. doi: 10.1093/intimm/dxy056.
15	Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus.Clin Rheumatol. 2017 Feb;36(2):335-341. doi: 10.1007/s10067-016-3508-2. Epub 2016 Dec 15.
16	Association of Serum Levels of Pentraxin-3, M-ficolin, and Surfactant Protein A with the Severity of Ischemic Stroke.Iran J Allergy Asthma Immunol. 2017 Apr;16(2):140-146.
17	Ficolin-1 is up-regulated in leukocytes and glomeruli from microscopic polyangiitis patients.Autoimmunity. 2013 Dec;46(8):513-24. doi: 10.3109/08916934.2013.822073. Epub 2013 Aug 15.
18	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
19	Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
20	Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
21	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
22	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.