Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GC46Y)

• DOT Name: Collectin-11 (COLEC11)
• Synonyms: Collectin kidney protein 1; CL-K1
• Gene Name: COLEC11
• Related Disease:
  3MC syndrome 2
  3MC syndrome 1
  Chagas disease
  Disseminated intravascular coagulation
  HIV infectious disease
  Nephropathy
  Bacterial infection
  3MC syndrome
  Pneumococcal infection
  Pneumonia
  Pneumonitis
  Schistosomiasis
• UniProt ID: COL11_HUMAN
• PDB ID: 4YLI; 4YMD
• Pfam ID: PF01391 ; PF00059
• Sequence:
  MRGNLALVGVLISLAFLSLLPSGHPQPAGDDACSVQILVPGLKGDAGEKGDKGAPGRPGR
  VGPTGEKGDMGDKGQKGSVGRHGKIGPIGSKGEKGDSGDIGPPGPNGEPGLPCECSQLRK
  AIGEMDNQVSQLTSELKFIKNAVAGVRETESKIYLLVKEEKRYADAQLSCQGRGGTLSMP
  KDEAANGLMAAYLAQAGLARVFIGINDLEKEGAFVYSDHSPMRTFNKWRSGEPNNAYDEE
  DCVEMVASGGWNDVACHTTMYFMCEFDKENM
• Function: Lectin that plays a role in innate immunity, apoptosis and embryogenesis. Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope. Primarily recognizes the terminal disaccharide of the glycan. Also recognizes a subset of fucosylated glycans and lipopolysaccharides. Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1. Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding (Probable). Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis.
• Tissue Specificity: Ubiquitous . Detected in adrenal gland, kidney, liver, ovaries and testis (at protein level) .
• KEGG Pathway: Phagosome (hsa04145)
• Reactome Pathway:
  Initial triggering of complement (R-HSA-166663)
  Scavenging by Class A Receptors (R-HSA-3000480)
  Lectin pathway of complement activation (R-HSA-166662)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
3MC syndrome 2	DISAXCJJ	Definitive	Autosomal recessive	[1]
3MC syndrome 1	DISXUNXN	Strong	Biomarker	[2]
Chagas disease	DIS8KNVF	Strong	Genetic Variation	[3]
Disseminated intravascular coagulation	DISCAVOZ	Strong	Altered Expression	[4]
HIV infectious disease	DISO97HC	Strong	Biomarker	[5]
Nephropathy	DISXWP4P	Strong	Biomarker	[6]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[7]
3MC syndrome	DISJUBAL	Supportive	Autosomal recessive	[2]
Pneumococcal infection	DIS6SXQD	Limited	Biomarker	[8]
Pneumonia	DIS8EF3M	Limited	Biomarker	[8]
Pneumonitis	DIS88E0K	Limited	Biomarker	[8]
Schistosomiasis	DIS6PD44	Limited	Altered Expression	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Collectin-11 (COLEC11).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collectin-11 (COLEC11).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Collectin-11 (COLEC11).	[12]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Collectin-11 (COLEC11).	[15]

2 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 decreases the methylation of Collectin-11 (COLEC11).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collectin-11 (COLEC11).	[14]

References

• [1] Ptosis of eyelids, strabismus, diastasis recti, hip defect, cryptorchidism, and developmental delay in two sibs. Am J Med Genet. 1989 Jun;33(2):186-9. doi: 10.1002/ajmg.1320330210.
• [2] Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011 Mar;43(3):197-203. doi: 10.1038/ng.757. Epub 2011 Jan 23.
• [3] Human collectin-11 (COLEC11) and its synergic genetic interaction with MASP2 are associated with the pathophysiology of Chagas Disease.PLoS Negl Trop Dis. 2019 Apr 17;13(4):e0007324. doi: 10.1371/journal.pntd.0007324. eCollection 2019 Apr.
• [4] Changes in Mannose-Binding Lectin and Collectin Kidney 1 Levels in Sepsis Patients With and Without Disseminated Intravascular Coagulation.Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029618821189. doi: 10.1177/1076029618821189.
• [5] The lectin pathway of complement: advantage or disadvantage in HIV pathogenesis?.Clin Immunol. 2014 Sep;154(1):13-25. doi: 10.1016/j.clim.2014.06.002. Epub 2014 Jun 11.
• [6] Collectins in urinary tract and kidney diseases.Int Urol Nephrol. 2018 Apr;50(4):695-703. doi: 10.1007/s11255-017-1728-2. Epub 2017 Oct 25.
• [7] Expression and functional characterization of collection-K1 from Nile tilapia (Oreochromis niloticus) in host innate immune defense.Mol Immunol. 2018 Nov;103:21-34. doi: 10.1016/j.molimm.2018.08.012. Epub 2018 Sep 3.
• [8] Collectin Kidney 1 Plays an Important Role in Innate Immunity against Streptococcus pneumoniae Infection.J Innate Immun. 2017;9(2):217-228. doi: 10.1159/000453316. Epub 2017 Jan 10.
• [9] Lectin complement protein Collectin 11 (CL-K1) and susceptibility to urinary schistosomiasis.PLoS Negl Trop Dis. 2015 Mar 25;9(3):e0003647. doi: 10.1371/journal.pntd.0003647. eCollection 2015 Mar.
• [10] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [13] 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.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.