Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIQTK9G)

• DOT Name: Collectin-12 (COLEC12)
• Synonyms: Collectin placenta protein 1; CL-P1; hCL-P1; Nurse cell scavenger receptor 2; Scavenger receptor class A member 4; Scavenger receptor with C-type lectin
• Gene Name: COLEC12
• Related Disease:
  Diabetic retinopathy
  Non-insulin dependent diabetes
  Arteriosclerosis
  Atherosclerosis
  Drug dependence
  Multiple sclerosis
  Myopathy
  Substance abuse
  Substance dependence
• UniProt ID: COL12_HUMAN
• PDB ID: 2OX8
• Pfam ID: PF01391 ; PF00059
• Sequence:
  MKDDFAEEEEVQSFGYKRFGIQEGTQCTKCKNNWALKFSIILLYILCALLTITVAILGYK
  VVEKMDNVTGGMETSRQTYDDKLTAVESDLKKLGDQTGKKAISTNSELSTFRSDILDLRQ
  QLREITEKTSKNKDTLEKLQASGDALVDRQSQLKETLENNSFLITTVNKTLQAYNGYVTN
  LQQDTSVLQGNLQNQMYSHNVVIMNLNNLNLTQVQQRNLITNLQRSVDDTSQAIQRIKND
  FQNLQQVFLQAKKDTDWLKEKVQSLQTLAANNSALAKANNDTLEDMNSQLNSFTGQMENI
  TTISQANEQNLKDLQDLHKDAENRTAIKFNQLEERFQLFETDIVNIISNISYTAHHLRTL
  TSNLNEVRTTCTDTLTKHTDDLTSLNNTLANIRLDSVSLRMQQDLMRSRLDTEVANLSVI
  MEEMKLVDSKHGQLIKNFTILQGPPGPRGPRGDRGSQGPPGPTGNKGQKGEKGEPGPPGP
  AGERGPIGPAGPPGERGGKGSKGSQGPKGSRGSPGKPGPQGSSGDPGPPGPPGKEGLPGP
  QGPPGFQGLQGTVGEPGVPGPRGLPGLPGVPGMPGPKGPPGPPGPSGAVVPLALQNEPTP
  APEDNGCPPHWKNFTDKCYYFSVEKEIFEDAKLFCEDKSSHLVFINTREEQQWIKKQMVG
  RESHWIGLTDSERENEWKWLDGTSPDYKNWKAGQPDNWGHGHGPGEDCAGLIYAGQWNDF
  QCEDVNNFICEKDRETVLSSAL
• Function: Scavenger receptor that displays several functions associated with host defense. Promotes binding and phagocytosis of Gram-positive, Gram-negative bacteria and yeast. Mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. Binds to several carbohydrates including Gal-type ligands, D-galactose, L- and D-fucose, GalNAc, T and Tn antigens in a calcium-dependent manner and internalizes specifically GalNAc in nurse-like cells. Binds also to sialyl Lewis X or a trisaccharide and asialo-orosomucoid (ASOR). May also play a role in the clearance of amyloid-beta in Alzheimer disease.
• Tissue Specificity: Expressed in perivascular macrophages. Expressed in plaques-surrounding reactive astrocytes and in perivascular astrocytes associated with cerebral amyloid angiopathy (CAA) in the temporal cortex of Alzheimer patient (at protein level). Strongly expressed in placenta. Moderately expressed in heart, skeletal muscle, small intestine and lung. Weakly expressed in brain, colon, thymus and kidney. Expressed in nurse-like cells. Expressed in reactive astrocytes and vascular/perivascular cells in the brain of Alzheimer patient.
• KEGG Pathway: Phagosome (hsa04145)
• Reactome Pathway:
  Scavenging by Class A Receptors (R-HSA-3000480)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[2]
Drug dependence	DIS9IXRC	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Myopathy	DISOWG27	Strong	Altered Expression	[5]
Substance abuse	DIS327VW	Strong	Biomarker	[3]
Substance dependence	DISDRAAR	Strong	Biomarker	[3]

22 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-12 (COLEC12).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collectin-12 (COLEC12).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collectin-12 (COLEC12).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collectin-12 (COLEC12).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Collectin-12 (COLEC12).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Collectin-12 (COLEC12).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Collectin-12 (COLEC12).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Collectin-12 (COLEC12).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Collectin-12 (COLEC12).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Collectin-12 (COLEC12).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Collectin-12 (COLEC12).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Collectin-12 (COLEC12).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Collectin-12 (COLEC12).	[16]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Collectin-12 (COLEC12).	[15]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Collectin-12 (COLEC12).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collectin-12 (COLEC12).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Collectin-12 (COLEC12).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Collectin-12 (COLEC12).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Collectin-12 (COLEC12).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collectin-12 (COLEC12).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Collectin-12 (COLEC12).	[21]
Choline	DM5D9YK	Investigative	Choline affects the expression of Collectin-12 (COLEC12).	[22]

References

• [1] Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes.Diabetologia. 2015 Jun;58(6):1231-8. doi: 10.1007/s00125-015-3569-9. Epub 2015 Mar 28.
• [2] The induction of human CL-P1 expression in hypoxia/reoxygenation culture condition and rat CL-P1 after ischemic/reperfusion treatment.Biochim Biophys Acta. 2011 Sep;1810(9):836-42. doi: 10.1016/j.bbagen.2011.06.013. Epub 2011 Jun 24.
• [3] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [4] Scavenger receptor collectin placenta 1 is a novel receptor involved in the uptake of myelin by phagocytes.Sci Rep. 2017 Mar 20;7:44794. doi: 10.1038/srep44794.
• [5] The atypical calpains: evolutionary analyses and roles in Caenorhabditis elegans cellular degeneration.PLoS Genet. 2012;8(3):e1002602. doi: 10.1371/journal.pgen.1002602. Epub 2012 Mar 29.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] 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.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [15] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [18] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [22] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.