Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI9RUDN)

• DOT Name: C-type lectin domain family 4 member K (CD207)
• Synonyms: Langerin; CD antigen CD207
• Gene Name: CD207
• Related Disease:
  Primary biliary cholangitis
  Atopic dermatitis
  Autoimmune disease
  Chronic obstructive pulmonary disease
  Dermatitis
  Dermatomyositis
  Diphtheria
  HIV infectious disease
  Hypospadias
  Idiopathic inflammatory myopathy
  Immunodeficiency
  Inflammatory bowel disease
  Measles
  Microphthalmia with limb anomalies
  Nasal polyp
  Osteoarthritis
  Pemphigus
  Polymyositis
  Ulcerative colitis
  Influenza
  Pulmonary emphysema
  Cutaneous melanoma
  Keratoconjunctivitis sicca
  Melanoma
  Nasopharyngeal carcinoma
  Neoplasm
  Thyroid gland papillary carcinoma
  Birbeck granule deficiency
• UniProt ID: CLC4K_HUMAN
• PDB ID: 3C22; 3KQG; 3P5D; 3P5E; 3P5F; 3P5G; 3P5H; 3P5I; 3P7F; 3P7G; 3P7H; 4AK8; 4N32; 4N33; 4N34; 4N35; 4N36; 4N37; 4N38; 5G6U; 7WZ8; 7YTQ
• Pfam ID: PF00059
• Sequence:
  MTVEKEAPDAHFTVDKQNISLWPREPPPKSGPSLVPGKTPTVRAALICLTLVLVASVLLQ
  AVLYPRFMGTISDVKTNVQLLKGRVDNISTLDSEIKKNSDGMEAAGVQIQMVNESLGYVR
  SQFLKLKTSVEKANAQIQILTRSWEEVSTLNAQIPELKSDLEKASALNTKIRALQGSLEN
  MSKLLKRQNDILQVVSQGWKYFKGNFYYFSLIPKTWYSAEQFCVSRNSHLTSVTSESEQE
  FLYKTAGGLIYWIGLTKAGMEGDWSWVDDTPFNKVQSVRFWIPGEPNNAGNNEHCGNIKA
  PSLQAWNDAPCDKTFLFICKRPYVPSEP
• Function: Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.
• Tissue Specificity: Exclusively expressed by Langerhans cells. Expressed in astrocytoma and malignant ependymoma, but not in normal brain tissues.
• Reactome Pathway: Cross-presentation of soluble exogenous antigens (endosomes) (R-HSA-1236978)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary biliary cholangitis	DIS43E0O	Definitive	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[4]
Dermatitis	DISY5SZC	Strong	Biomarker	[5]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[6]
Diphtheria	DISZWM55	Strong	Altered Expression	[7]
HIV infectious disease	DISO97HC	Strong	Biomarker	[8]
Hypospadias	DIS48CCP	Strong	Biomarker	[9]
Idiopathic inflammatory myopathy	DISGB1BZ	Strong	Altered Expression	[6]
Immunodeficiency	DIS093I0	Strong	Biomarker	[10]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[11]
Measles	DISXSUID	Strong	Biomarker	[12]
Microphthalmia with limb anomalies	DIS19E4H	Strong	Biomarker	[13]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[14]
Osteoarthritis	DIS05URM	Strong	Biomarker	[13]
Pemphigus	DISZAZ6M	Strong	Biomarker	[3]
Polymyositis	DIS5DHFP	Strong	Altered Expression	[6]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[15]
Influenza	DIS3PNU3	moderate	Biomarker	[16]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[4]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[17]
Keratoconjunctivitis sicca	DISNOENH	Limited	Biomarker	[18]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[20]
Neoplasm	DISZKGEW	Limited	Biomarker	[21]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[22]
Birbeck granule deficiency	DISFEL2F	No Known	Autosomal dominant	[23]

1 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 increases the methylation of C-type lectin domain family 4 member K (CD207).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One	DMDN12L	Investigative	2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One decreases the expression of C-type lectin domain family 4 member K (CD207).	[25]

References

• [1] Significance of periductal Langerhans cells and biliary epithelial cell-derived macrophage inflammatory protein-3 in the pathogenesis of primary biliary cirrhosis.Liver Int. 2011 Feb;31(2):245-53. doi: 10.1111/j.1478-3231.2010.02367.x. Epub 2010 Nov 24.
• [2] Toll-like receptor 4 attenuates a murine model of atopic dermatitis through inhibition of langerin-positive DCs migration.Exp Dermatol. 2018 Sep;27(9):1015-1022. doi: 10.1111/exd.13698. Epub 2018 Jul 20.
• [3] Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells.EBioMedicine. 2018 Jan;27:293-303. doi: 10.1016/j.ebiom.2017.12.022. Epub 2017 Dec 20.
• [4] Implication of C-type lectin receptor langerin and keratan sulfate disaccharide in emphysema.Cell Immunol. 2018 Nov;333:80-84. doi: 10.1016/j.cellimm.2018.07.004. Epub 2018 Jul 17.
• [5] The C-type lectin receptor MGL senses N-acetylgalactosamine on the unique Staphylococcus aureus ST395 wall teichoic acid.Cell Microbiol. 2019 Oct;21(10):e13072. doi: 10.1111/cmi.13072. Epub 2019 Jul 8.
• [6] Fascin-expressing dendritic cells dominate in polymyositis and dermatomyositis.J Rheumatol. 2013 Feb;40(2):186-91. doi: 10.3899/jrheum.120590. Epub 2012 Nov 1.
• [7] Langerin(+) CD8(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection.Front Immunol. 2018 May 7;9:953. doi: 10.3389/fimmu.2018.00953. eCollection 2018.
• [8] A high mucosal blocking score is associated with HIV protection.AIDS. 2019 Mar 1;33(3):411-423. doi: 10.1097/QAD.0000000000002099.
• [9] Langerhans cells in hypospadias: an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections.BMC Urol. 2019 Nov 12;19(1):114. doi: 10.1186/s12894-019-0551-8.
• [10] Bispecific chimeric antigen receptors targeting the CD4 binding site and high-mannose Glycans of gp120 optimized for anti-human immunodeficiency virus potency and breadth with minimal immunogenicity.Cytotherapy. 2018 Mar;20(3):407-419. doi: 10.1016/j.jcyt.2017.11.001. Epub 2018 Jan 3.
• [11] Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients.Inflamm Bowel Dis. 2014 Mar;20(3):525-33. doi: 10.1097/01.MIB.0000442011.60285.68.
• [12] Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4?T cells but are incapable of cross-presentation.Eur J Immunol. 2011 Sep;41(9):2619-31. doi: 10.1002/eji.201041305. Epub 2011 Aug 8.
• [13] Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells.Allergy. 2015 Apr;70(4):408-19. doi: 10.1111/all.12576.
• [14] Elevated presence of myeloid dendritic cells in nasal polyps of patients with chronic rhinosinusitis.Clin Exp Allergy. 2015 Feb;45(2):384-93. doi: 10.1111/cea.12471.
• [15] Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp.Mol Nutr Food Res. 2014 May;58(5):1132-43. doi: 10.1002/mnfr.201300596. Epub 2013 Dec 18.
• [16] Enhanced Immune Responses Conferring Cross-Protection by Skin Vaccination With a Tri-Component Influenza Vaccine Using a Microneedle Patch.Front Immunol. 2018 Jul 30;9:1705. doi: 10.3389/fimmu.2018.01705. eCollection 2018.
• [17] CD207+/langerin positive dendritic cells in invasive and in situ cutaneous malignant melanoma.Postepy Dermatol Alergol. 2017 Jun;34(3):233-239. doi: 10.5114/ada.2017.67845. Epub 2017 May 29.
• [18] Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease.PLoS One. 2017 Apr 25;12(4):e0176153. doi: 10.1371/journal.pone.0176153. eCollection 2017.
• [19] Glyco-Dendrimers as Intradermal Anti-Tumor Vaccine Targeting Multiple Skin DC Subsets.Theranostics. 2019 Aug 12;9(20):5797-5809. doi: 10.7150/thno.35059. eCollection 2019.
• [20] Dendritic cell subpopulations in nasopharyngeal cancer.Oncol Lett. 2019 Feb;17(2):2557-2561. doi: 10.3892/ol.2018.9835. Epub 2018 Dec 14.
• [21] In melanoma changes of immature and mature dendritic cell expression correlate with tumor thickness:an immunohistochemical study.Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2):325-33. doi: 10.1177/039463200702000212.
• [22] Association of CD1a-positive dendritic cells with papillary thyroid carcinoma in thyroid fine-needle aspirations: a cytologic and immunocytochemical evaluation.Cancer Cytopathol. 2013 Apr;121(4):206-13. doi: 10.1002/cncy.21239. Epub 2012 Oct 5.
• [23] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [24] 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.
• [25] Implication of the MAPK pathways in the maturation of human dendritic cells induced by nickel and TNF-alpha. Toxicology. 2005 Jan 15;206(2):233-44. doi: 10.1016/j.tox.2004.08.015.