Details of Drug Off-Target (DOT)

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

• DOT Name: Collectin-10 (COLEC10)
• Synonyms: Collectin liver protein 1; CL-L1; Collectin-34; CL-34
• Gene Name: COLEC10
• Related Disease:
  Hepatocellular carcinoma
  Acute lymphocytic leukaemia
  Acute undifferentiated leukemia
  Advanced cancer
  Childhood myelodysplastic syndrome
  Myelodysplastic syndrome
  Neoplasm
  Plasma cell myeloma
  Small lymphocytic lymphoma
  Waldenstrom macroglobulinemia
  3MC syndrome
  Basal cell carcinoma
  Basal cell neoplasm
• UniProt ID: COL10_HUMAN
• Pfam ID: PF01391 ; PF00059
• Sequence:
  MNGFASLLRRNQFILLVLFLLQIQSLGLDIDSRPTAEVCATHTISPGPKGDDGEKGDPGE
  EGKHGKVGRMGPKGIKGELGDMGDQGNIGKTGPIGKKGDKGEKGLLGIPGEKGKAGTVCD
  CGRYRKFVGQLDISIARLKTSMKFVKNVIAGIRETEEKFYYIVQEEKNYRESLTHCRIRG
  GMLAMPKDEAANTLIADYVAKSGFFRVFIGVNDLEREGQYMFTDNTPLQNYSNWNEGEPS
  DPYGHEDCVEMLSSGRWNDTECHLTMYFVCEFIKKKK
• Function: Lectin that binds to various sugars: galactose > mannose = fucose > N-acetylglucosamine > N-acetylgalactosamine. Acts as a chemoattractant, probably involved in the regulation of cell migration.
• Tissue Specificity: Highly expressed in liver, placenta and adrenal gland. Moderately expressed in small intestine, lung, stomach and prostate. Weakly expressed in trachea and spleen.
• Reactome Pathway:
  Initial triggering of complement (R-HSA-166663)
  Lectin pathway of complement activation (R-HSA-166662)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[2]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[6]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[7]
Waldenstrom macroglobulinemia	DIS9O23I	Strong	Genetic Variation	[6]
3MC syndrome	DISJUBAL	Supportive	Autosomal recessive	[8]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[9]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Collectin-10 (COLEC10).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Collectin-10 (COLEC10).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Collectin-10 (COLEC10).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collectin-10 (COLEC10).	[13]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] C-type lectin-like molecule-1: a novel myeloid cell surface marker associated with acute myeloid leukemia.Cancer Res. 2004 Nov 15;64(22):8443-50. doi: 10.1158/0008-5472.CAN-04-1659.
• [3] Daunorubicin-containing CLL1-targeting nanomicelles have anti-leukemia stem cell activity in acute myeloid leukemia.Nanomedicine. 2019 Aug;20:102004. doi: 10.1016/j.nano.2019.04.007. Epub 2019 May 2.
• [4] Chimeric CLL-1 antibody fusion proteins containing granulocyte-macrophage colony-stimulating factor or interleukin-2 with specificity for B-cell malignancies exhibit enhanced effector functions while retaining tumor targeting properties.Blood. 1997 Jun 15;89(12):4437-47.
• [5] CLT030, a leukemic stem cell-targeting CLL1 antibody-drug conjugate for treatment of acute myeloid leukemia. Blood Adv. 2018 Jul 24;2(14):1738-1749.
• [6] MYD88 L265P in Waldenstrm macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction.Blood. 2013 Mar 14;121(11):2051-8. doi: 10.1182/blood-2012-09-454355. Epub 2013 Jan 15.
• [7] Comparative assessment of prognostic models in chronic lymphocytic leukemia: evaluation in Indian cohort.Ann Hematol. 2019 Feb;98(2):437-443. doi: 10.1007/s00277-018-3525-0. Epub 2018 Oct 18.
• [8] COLEC10 is mutated in 3MC patients and regulates early craniofacial development. PLoS Genet. 2017 Mar 16;13(3):e1006679. doi: 10.1371/journal.pgen.1006679. eCollection 2017 Mar.
• [9] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [12] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [13] 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.