Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT7X1UC)

DOT Name C-type lectin domain family 4 member D (CLEC4D)
Synonyms C-type lectin superfamily member 8; C-type lectin-like receptor 6; CLEC-6; Dendritic cell-associated C-type lectin 3; DC-associated C-type lectin 3; Dectin-3; CD antigen CD368
Gene Name CLEC4D
Related Disease
Acute myelogenous leukaemia ( )
Acute lymphocytic leukaemia ( )
Adult lymphoma ( )
Advanced cancer ( )
Allergic rhinitis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Burkitt lymphoma ( )
Childhood acute lymphoblastic leukemia ( )
Colitis ( )
Crohn disease ( )
Cryptococcosis ( )
Cutaneous leishmaniasis ( )
Late-onset Parkinson disease ( )
Leukemia ( )
Lymphoproliferative syndrome ( )
Mucocutaneous leishmaniasis ( )
Multiple sclerosis ( )
Neoplasm ( )
Osteoarthritis ( )
Pediatric lymphoma ( )
Promyelocytic leukaemia ( )
Schizophrenia ( )
Sinusitis ( )
Small lymphocytic lymphoma ( )
Systemic mastocytosis ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Tuberculosis ( )
Visceral leishmaniasis ( )
Chronic otitis media ( )
Plasma cell myeloma ( )
Pulmonary emphysema ( )
B-cell neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Follicular lymphoma ( )
Lymphoma ( )
Lymphoma, non-Hodgkin, familial ( )
Neuroblastoma ( )
Non-hodgkin lymphoma ( )
Pulmonary disease ( )
Rectal carcinoma ( )
UniProt ID
CLC4D_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2LS8; 3WHD
Pfam ID
PF00059
Sequence
MGLEKPQSKLEGGMHPQLIPSVIAVVFILLLSVCFIASCLVTHHNFSRCKRGTGVHKLEH
HAKLKCIKEKSELKSAEGSTWNCCPIDWRAFQSNCYFPLTDNKTWAESERNCSGMGAHLM
TISTEAEQNFIIQFLDRRLSYFLGLRDENAKGQWRWVDQTPFNPRRVFWHKNEPDNSQGE
NCVVLVYNQDKWAWNDVPCNFEASRICKIPGTTLN
Function
Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of pathogen-associated molecular patterns (PAMPs) of bacteria and fungi. The PAMPs include alpha-mannans on C.albicans hypheas and mycobacterial trehalose 6,6'-dimycolate (TDM). Interacts with signaling adapter Fc receptor gamma chain/FCER1G, likely via CLEC4E, to form a functional complex in myeloid cells. Binding of mycobacterial TDM or C.albicans alpha-mannans to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes. The heterodimer formed with CLEC6A is active against fungal infection. Functions as an endocytic receptor. May be involved in antigen uptake at the site of infection, either for clearance of the antigen, or for processing and further presentation to T-cells.
Tissue Specificity Expressed weakly in peripheral blood leukocytes, bone marrow and spleen. Expression is confined mostly in monocytes and macrophage and seems to be up-regulated by IL-6, IL-10, TNF-alpha and IFN-gamma.
KEGG Pathway
C-type lectin receptor sig.ling pathway (hsa04625 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Dectin-2 family (R-HSA-5621480 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Definitive Biomarker [1]
Acute lymphocytic leukaemia DISPX75S Strong Biomarker [2]
Adult lymphoma DISK8IZR Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Allergic rhinitis DIS3U9HN Strong Altered Expression [5]
Arteriosclerosis DISK5QGC Strong Biomarker [6]
Atherosclerosis DISMN9J3 Strong Biomarker [6]
Autoimmune disease DISORMTM Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Genetic Variation [9]
Burkitt lymphoma DIS9D5XU Strong Biomarker [10]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [2]
Colitis DISAF7DD Strong Biomarker [11]
Crohn disease DIS2C5Q8 Strong Altered Expression [12]
Cryptococcosis DISDYDTK Strong Biomarker [13]
Cutaneous leishmaniasis DISRK7TS Strong Biomarker [14]
Late-onset Parkinson disease DIS9IOUI Strong Biomarker [15]
Leukemia DISNAKFL Strong Genetic Variation [16]
Lymphoproliferative syndrome DISMVL8O Strong Altered Expression [17]
Mucocutaneous leishmaniasis DISQEME2 Strong Biomarker [18]
Multiple sclerosis DISB2WZI Strong Biomarker [7]
Neoplasm DISZKGEW Strong Biomarker [8]
Osteoarthritis DIS05URM Strong Genetic Variation [19]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [3]
Promyelocytic leukaemia DISYGG13 Strong Genetic Variation [20]
Schizophrenia DISSRV2N Strong Biomarker [15]
Sinusitis DISX5NCF Strong Altered Expression [5]
Small lymphocytic lymphoma DIS30POX Strong Genetic Variation [21]
Systemic mastocytosis DISNQ2OY Strong Genetic Variation [22]
Thyroid cancer DIS3VLDH Strong Genetic Variation [9]
Thyroid gland carcinoma DISMNGZ0 Strong Genetic Variation [9]
Tuberculosis DIS2YIMD Strong Biomarker [23]
Visceral leishmaniasis DISTKEYK Strong Biomarker [24]
Chronic otitis media DIS3P3TG moderate Altered Expression [25]
Plasma cell myeloma DIS0DFZ0 moderate Altered Expression [26]
Pulmonary emphysema DIS5M7HZ moderate Biomarker [27]
B-cell neoplasm DISVY326 Limited Biomarker [28]
Colon cancer DISVC52G Limited Genetic Variation [29]
Colon carcinoma DISJYKUO Limited Genetic Variation [29]
Follicular lymphoma DISVEUR6 Limited Genetic Variation [30]
Lymphoma DISN6V4S Limited Altered Expression [3]
Lymphoma, non-Hodgkin, familial DISCXYIZ Limited Biomarker [31]
Neuroblastoma DISVZBI4 Limited Biomarker [32]
Non-hodgkin lymphoma DISS2Y8A Limited Biomarker [31]
Pulmonary disease DIS6060I Limited Biomarker [33]
Rectal carcinoma DIS8FRR7 Limited Genetic Variation [29]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) 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
Valproate DMCFE9I Approved Valproate increases the expression of C-type lectin domain family 4 member D (CLEC4D). [34]
Tretinoin DM49DUI Approved Tretinoin increases the expression of C-type lectin domain family 4 member D (CLEC4D). [35]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of C-type lectin domain family 4 member D (CLEC4D). [39]
Paraquat DMR8O3X Investigative Paraquat decreases the expression of C-type lectin domain family 4 member D (CLEC4D). [40]
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3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of C-type lectin domain family 4 member D (CLEC4D). [36]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of C-type lectin domain family 4 member D (CLEC4D). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of C-type lectin domain family 4 member D (CLEC4D). [38]
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References

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13 Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis.Front Immunol. 2018 Aug 6;9:1781. doi: 10.3389/fimmu.2018.01781. eCollection 2018.
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