Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO38TRG)

DOT Name C-type lectin domain family 1 member B (CLEC1B)
Synonyms C-type lectin-like receptor 2; CLEC-2
Gene Name CLEC1B
Related Disease
Gastric cancer ( )
Hematologic disease ( )
Hemolytic-uremic syndrome ( )
Stomach cancer ( )
Thrombotic microangiopathy ( )
Thrombotic thrombocytopenic purpura ( )
Acute coronary syndrome ( )
Adult respiratory distress syndrome ( )
Alzheimer disease ( )
Androgen insensitivity syndrome ( )
Autoimmune thrombocytopenia ( )
Clear cell renal carcinoma ( )
Coagulation defect ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Hepatocellular carcinoma ( )
Idiopathic thrombocytopenic purpura ( )
Immune thrombocytopenia ( )
Lung neoplasm ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Pneumonia ( )
Pneumonitis ( )
Stroke ( )
Thrombocytopenia ( )
Venous thromboembolism ( )
Advanced cancer ( )
Rheumatoid arthritis ( )
Type-1/2 diabetes ( )
UniProt ID
CLC1B_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2C6U; 3WSR; 3WWK
Pfam ID
PF00059
Sequence
MQDEDGYITLNIKTRKPALISVGSASSSWWRVMALILLILCVGMVVGLVALGIWSVMQRN
YLQGENENRTGTLQQLAKRFCQYVVKQSELKGTFKGHKCSPCDTNWRYYGDSCYGFFRHN
LTWEESKQYCTDMNATLLKIDNRNIVEYIKARTHLIRWVGLSRQKSNEVWKWEDGSVISE
NMFEFLEDGKGNMNCAYFHNGKMHPTFCENKHYLMCERKAGMTKVDQLP
Function
C-type lectin-like receptor that functions as a platelet receptor for the lymphatic endothelial marker, PDPN. After ligand activation, signals via sequential activation of SRC and SYK tyrosine kinases leading to activation of PLCG2 ; (Microbial infection) Acts as a receptor for the platelet-aggregating snake venom protein rhodocytin. Rhodocytin binding leads to tyrosine phosphorylation and this promotes the binding of spleen tyrosine kinase (SYK) and initiation of downstream tyrosine phosphorylation events and activation of PLCG2 ; (Microbial infection) Acts as an attachment factor for Human immunodeficiency virus type 1 (HIV-1) and facilitates its capture by platelets.
Tissue Specificity Expressed preferentially in the liver. Also expressed in immune cells of myeloid origin and on the surface of platelets.
KEGG Pathway
C-type lectin receptor sig.ling pathway (hsa04625 )
Reactome Pathway
Heme signaling (R-HSA-9707616 )
GPVI-mediated activation cascade (R-HSA-114604 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Gastric cancer DISXGOUK Definitive Altered Expression [1]
Hematologic disease DIS9XD9A Definitive Altered Expression [2]
Hemolytic-uremic syndrome DISSCBGW Definitive Altered Expression [2]
Stomach cancer DISKIJSX Definitive Altered Expression [1]
Thrombotic microangiopathy DISLZ0VW Definitive Altered Expression [2]
Thrombotic thrombocytopenic purpura DIS3LDOU Definitive Altered Expression [2]
Acute coronary syndrome DIS7DYEW Strong Biomarker [3]
Adult respiratory distress syndrome DISIJV47 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Altered Expression [5]
Androgen insensitivity syndrome DISUZBBO Strong Biomarker [6]
Autoimmune thrombocytopenia DISNF0OI Strong Biomarker [7]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [8]
Coagulation defect DIS9X3H6 Strong Biomarker [9]
Coronary atherosclerosis DISKNDYU Strong Biomarker [10]
Coronary heart disease DIS5OIP1 Strong Biomarker [10]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Idiopathic thrombocytopenic purpura DISFKGJU Strong Biomarker [7]
Immune thrombocytopenia DISVCBNS Strong Biomarker [7]
Lung neoplasm DISVARNB Strong Biomarker [12]
Melanoma DIS1RRCY Strong Biomarker [13]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [14]
Neoplasm DISZKGEW Strong Biomarker [15]
Pneumonia DIS8EF3M Strong Biomarker [16]
Pneumonitis DIS88E0K Strong Biomarker [4]
Stroke DISX6UHX Strong Biomarker [6]
Thrombocytopenia DISU61YW Strong Biomarker [12]
Venous thromboembolism DISUR7CR Strong Biomarker [17]
Advanced cancer DISAT1Z9 Limited Altered Expression [18]
Rheumatoid arthritis DISTSB4J Limited Biomarker [19]
Type-1/2 diabetes DISIUHAP Limited Biomarker [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 30 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of C-type lectin domain family 1 member B (CLEC1B). [21]
------------------------------------------------------------------------------------

References

1 Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-1 via CLEC-2.Glycobiology. 2020 Apr 20;30(5):301-311. doi: 10.1093/glycob/cwz097.
2 Elevated plasma levels of soluble C-type lectin-like receptor 2 (CLEC2) in patients with thrombotic microangiopathy.Thromb Res. 2019 Jun;178:54-58. doi: 10.1016/j.thromres.2019.03.018. Epub 2019 Mar 28.
3 Soluble CLEC-2 is generated independently of ADAM10 and is increased in plasma in acute coronary syndrome: comparison with soluble GPVI.Int J Hematol. 2019 Sep;110(3):285-294. doi: 10.1007/s12185-019-02680-4. Epub 2019 Jun 5.
4 Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse.Am J Physiol Lung Cell Mol Physiol. 2017 Dec 1;313(6):L1016-L1029. doi: 10.1152/ajplung.00023.2017. Epub 2017 Aug 24.
5 C-type lectin-like receptor 2 and zonulin are associated with mild cognitive impairment and Alzheimer's disease.Acta Neurol Scand. 2020 Mar;141(3):250-255. doi: 10.1111/ane.13196. Epub 2019 Nov 25.
6 Plasma C-type lectin-like receptor 2 as a predictor of death and vascular events in patients with acute ischemic stroke.Eur J Neurol. 2019 Oct;26(10):1334-1340. doi: 10.1111/ene.13984. Epub 2019 Jun 17.
7 Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia.Thromb Haemost. 2018 Jun;118(6):1009-1020. doi: 10.1055/s-0038-1646924. Epub 2018 Apr 25.
8 High CLEC-2 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma.Oncotarget. 2016 Sep 27;7(39):63661-63668. doi: 10.18632/oncotarget.11606.
9 Essential in vivo roles of the platelet activation receptor CLEC-2 in tumour metastasis, lymphangiogenesis and thrombus formation.J Biochem. 2011 Aug;150(2):127-32. doi: 10.1093/jb/mvr079. Epub 2011 Jun 21.
10 Plasma soluble C-type lectin-like receptor-2 is associated with the risk of coronary artery disease.Front Med. 2020 Feb;14(1):81-90. doi: 10.1007/s11684-019-0692-x. Epub 2019 Jul 6.
11 CLEC1B Expression and PD-L1 Expression Predict Clinical Outcome in Hepatocellular Carcinoma with Tumor Hemorrhage.Transl Oncol. 2018 Apr;11(2):552-558. doi: 10.1016/j.tranon.2018.02.010. Epub 2018 Mar 8.
12 Roles of the CLEC-2-podoplanin interaction in tumor progression.Platelets. 2018 Jun 4:1-7. doi: 10.1080/09537104.2018.1478401. Online ahead of print.
13 Blocking podoplanin suppresses growth and pulmonary metastasis of human malignant melanoma.BMC Cancer. 2019 Jun 17;19(1):599. doi: 10.1186/s12885-019-5808-9.
14 Functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks CLEC-2/podoplanin-dependent platelet aggregation and lung metastasis.J Thromb Haemost. 2018 May;16(5):960-972. doi: 10.1111/jth.13987. Epub 2018 Mar 30.
15 A pull-down and slot blot-based screening system for inhibitor compounds of the podoplanin-CLEC-2 interaction.PLoS One. 2019 Sep 25;14(9):e0222331. doi: 10.1371/journal.pone.0222331. eCollection 2019.
16 Platelet glycoprotein VI aids in local immunity during pneumonia-derived sepsis caused by gram-negative bacteria.Blood. 2018 Feb 22;131(8):864-876. doi: 10.1182/blood-2017-06-788067. Epub 2017 Nov 29.
17 The role of podoplanin in cancer-associated thrombosis.Thromb Res. 2018 Apr;164 Suppl 1:S34-S39. doi: 10.1016/j.thromres.2018.01.020.
18 Functional significance of the platelet immune receptors GPVI and CLEC-2.J Clin Invest. 2019 Jan 2;129(1):12-23. doi: 10.1172/JCI122955. Epub 2019 Jan 2.
19 Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.PLoS One. 2014 Jun 16;9(6):e99607. doi: 10.1371/journal.pone.0099607. eCollection 2014.
20 Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization.EBioMedicine. 2015 Feb 25;2(3):214-24. doi: 10.1016/j.ebiom.2015.02.013. eCollection 2015 Mar.
21 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.