Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ2959Y)

DOT Name Killer cell lectin-like receptor subfamily B member 1 (KLRB1)
Synonyms C-type lectin domain family 5 member B; HNKR-P1a; NKR-P1A; Natural killer cell surface protein P1A; CD antigen CD161
Gene Name KLRB1
Related Disease
Peeling skin syndrome 1 ( )
Potocki-Shaffer syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Psoriatic arthritis ( )
Systemic sclerosis ( )
T lymphoblastic leukaemia ( )
Advanced cancer ( )
Anca-associated vasculitis ( )
Cytomegalovirus infection ( )
Eclampsia ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Hepatitis B virus infection ( )
Hidradenitis suppurativa ( )
HIV infectious disease ( )
Influenza ( )
Intermittent claudication ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Multiple sclerosis ( )
Non-small-cell lung cancer ( )
Promyelocytic leukaemia ( )
Rheumatoid arthritis ( )
Systemic lupus erythematosus ( )
Triple negative breast cancer ( )
Tuberculosis ( )
Fetal growth restriction ( )
Gastrointestinal mucositis ( )
Immune system disorder ( )
Lymphoproliferative syndrome ( )
Plasma cell myeloma ( )
Asthma ( )
Capillary malformation ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Inflammation ( )
Neoplasm ( )
Osteoarthritis ( )
Periodontitis ( )
Urinary bladder neoplasm ( )
UniProt ID
KLRB1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5MGR; 5MGS; 5MGT
Pfam ID
PF00059
Sequence
MDQQAIYAELNLPTDSGPESSSPSSLPRDVCQGSPWHQFALKLSCAGIILLVLVVTGLSV
SVTSLIQKSSIEKCSVDIQQSRNKTTERPGLLNCPIYWQQLREKCLLFSHTVNPWNNSLA
DCSTKESSLLLIRDKDELIHTQNLIRDKAILFWIGLNFSLSEKNWKWINGSFLNSNDLEI
RGDAKENSCISISQTSVYSEYCSTEIRWICQKELTPVRNKVYPDS
Function
Plays an inhibitory role on natural killer (NK) cells cytotoxicity. Activation results in specific acid sphingomyelinase/SMPD1 stimulation with subsequent marked elevation of intracellular ceramide. Activation also leads to AKT1/PKB and RPS6KA1/RSK1 kinases stimulation as well as markedly enhanced T-cell proliferation induced by anti-CD3. Acts as a lectin that binds to the terminal carbohydrate Gal-alpha(1,3)Gal epitope as well as to the N-acetyllactosamine epitope. Binds also to CLEC2D/LLT1 as a ligand and inhibits NK cell-mediated cytotoxicity as well as interferon-gamma secretion in target cells.
Tissue Specificity Expressed in a subset of NK cells predominantly in intestinal epithelium and liver. Detected in peripheral blood T-cells and preferentially in adult T-cells with a memory antigenic phenotype.
KEGG Pathway
Malaria (hsa05144 )
Reactome Pathway
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Peeling skin syndrome 1 DIS35574 Definitive Biomarker [1]
Potocki-Shaffer syndrome DISKGU59 Definitive Biomarker [1]
Prostate cancer DISF190Y Definitive Biomarker [2]
Prostate carcinoma DISMJPLE Definitive Biomarker [2]
Psoriatic arthritis DISLWTG2 Definitive Altered Expression [3]
Systemic sclerosis DISF44L6 Definitive Biomarker [1]
T lymphoblastic leukaemia DIS2PNPP Definitive Altered Expression [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Anca-associated vasculitis DISU3CNU Strong Biomarker [6]
Cytomegalovirus infection DISCEMGC Strong Altered Expression [7]
Eclampsia DISWPO8U Strong Biomarker [8]
Hepatitis DISXXX35 Strong Biomarker [9]
Hepatitis A virus infection DISUMFQV Strong Biomarker [9]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [10]
Hidradenitis suppurativa DIS3ZNAK Strong Altered Expression [11]
HIV infectious disease DISO97HC Strong Altered Expression [12]
Influenza DIS3PNU3 Strong Biomarker [10]
Intermittent claudication DISGY3B0 Strong Genetic Variation [13]
Lung cancer DISCM4YA Strong Altered Expression [14]
Lung carcinoma DISTR26C Strong Altered Expression [14]
Melanoma DIS1RRCY Strong Biomarker [15]
Multiple sclerosis DISB2WZI Strong Altered Expression [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [14]
Promyelocytic leukaemia DISYGG13 Strong Biomarker [17]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [18]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [19]
Triple negative breast cancer DISAMG6N Strong Biomarker [20]
Tuberculosis DIS2YIMD Strong Altered Expression [21]
Fetal growth restriction DIS5WEJ5 moderate Genetic Variation [22]
Gastrointestinal mucositis DIS140OB moderate Biomarker [23]
Immune system disorder DISAEGPH moderate Biomarker [24]
Lymphoproliferative syndrome DISMVL8O moderate Altered Expression [25]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [23]
Asthma DISW9QNS Limited Biomarker [26]
Capillary malformation DISR6ZSG Limited Biomarker [27]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [28]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [29]
Inflammation DISJUQ5T Limited Altered Expression [30]
Neoplasm DISZKGEW Limited Biomarker [14]
Osteoarthritis DIS05URM Limited Altered Expression [31]
Periodontitis DISI9JOI Limited Biomarker [32]
Urinary bladder neoplasm DIS7HACE Limited Biomarker [33]
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⏷ Show the Full List of 42 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
Aspirin DM672AH Approved Aspirin increases the expression of Killer cell lectin-like receptor subfamily B member 1 (KLRB1). [34]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of Killer cell lectin-like receptor subfamily B member 1 (KLRB1). [35]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Killer cell lectin-like receptor subfamily B member 1 (KLRB1). [36]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Killer cell lectin-like receptor subfamily B member 1 (KLRB1). [37]
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References

1 Clinical relevance of ROR positive and negative subsets of CD161+CD4+ T cells in primary Sjgren's syndrome.Rheumatology (Oxford). 2017 Feb;56(2):303-312. doi: 10.1093/rheumatology/kew360. Epub 2016 Nov 1.
2 Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction.Oncotarget. 2016 Oct 18;7(42):68650-68661. doi: 10.18632/oncotarget.11896.
3 Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis.Arthritis Rheumatol. 2020 Mar;72(3):435-447. doi: 10.1002/art.41156. Epub 2020 Feb 4.
4 CD161 Is Expressed in a Subset of T-Cell Prolymphocytic Leukemia Cases and Is Useful for Disease Follow-up.Am J Clin Pathol. 2019 Sep 9;152(4):471-478. doi: 10.1093/ajcp/aqz060.
5 Biological and Clinical Significance of Human NKRP1A/LLT1 Receptor/Ligand Interactions.Crit Rev Immunol. 2018;38(6):479-489. doi: 10.1615/CritRevImmunol.2019029559.
6 Environmental factor and inflammation-driven alteration of the total peripheral T-cell compartment in granulomatosis with polyangiitis.J Autoimmun. 2017 Mar;78:79-91. doi: 10.1016/j.jaut.2016.12.004. Epub 2016 Dec 28.
7 Differential Effect of Cytomegalovirus Infection with Age on the Expression of CD57, CD300a, and CD161 on T-Cell Subpopulations.Front Immunol. 2017 Jun 2;8:649. doi: 10.3389/fimmu.2017.00649. eCollection 2017.
8 The possible role of CD8+/V7.2+/CD161++ T (MAIT) and CD8+/V7.2+/CD161(lo) T (MAIT-like) cells in the pathogenesis of early-onset pre-eclampsia.Am J Reprod Immunol. 2018 Feb;79(2). doi: 10.1111/aji.12805. Epub 2017 Dec 19.
9 Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cells.J Immunol. 2004 Aug 1;173(3):2159-66. doi: 10.4049/jimmunol.173.3.2159.
10 CD161 expression on hepatitis C virus-specific CD8+ T cells suggests a distinct pathway of T cell differentiation.Hepatology. 2008 Feb;47(2):396-406. doi: 10.1002/hep.22040.
11 Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy.J Invest Dermatol. 2017 Nov;137(11):2389-2395. doi: 10.1016/j.jid.2017.05.033. Epub 2017 Jun 23.
12 Using safe, affordable and accessible non-steroidal anti-inflammatory drugs to reduce the number of HIV target cells in the blood and at the female genital tract.J Int AIDS Soc. 2018 Jul;21(7):e25150. doi: 10.1002/jia2.25150.
13 Relationship of the platelet glycoprotein PlA and fibrinogen T/G+1689 polymorphisms with peripheral arterial disease and ischaemic heart disease.Thromb Res. 2003;112(4):209-16. doi: 10.1016/j.thromres.2003.11.010.
14 Expression of LLT1 and its receptor CD161 in lung cancer is associated with better clinical outcome.Oncoimmunology. 2018 Jan 29;7(5):e1423184. doi: 10.1080/2162402X.2017.1423184. eCollection 2018.
15 Low expression of CD161 and NKG2D activating NK receptor is associated with impaired NK cell cytotoxicity in metastatic melanoma patients.Clin Exp Metastasis. 2007;24(1):1-11. doi: 10.1007/s10585-006-9043-9. Epub 2007 Feb 13.
16 An intermediate level of CD161 expression defines a novel activated, inflammatory, and pathogenic subset of CD8(+) T cells involved in multiple sclerosis.J Autoimmun. 2018 Mar;88:61-74. doi: 10.1016/j.jaut.2017.10.005. Epub 2017 Oct 18.
17 Human CD5(+) Innate Lymphoid Cells Are Functionally Immature and Their Development from CD34(+) Progenitor Cells Is Regulated by Id2.Front Immunol. 2017 Aug 31;8:1047. doi: 10.3389/fimmu.2017.01047. eCollection 2017.
18 Altered composition and phenotype of mucosal-associated invariant T cells in early untreated rheumatoid arthritis.Arthritis Res Ther. 2019 Jan 5;21(1):3. doi: 10.1186/s13075-018-1799-1.
19 Analysis of the CD161-expressing cell quantities and CD161 expression levels in peripheral blood natural killer and T cells of systemic lupus erythematosus patients.Clin Exp Med. 2017 Feb;17(1):101-109. doi: 10.1007/s10238-015-0402-1. Epub 2015 Nov 21.
20 Blocking LLT1 (CLEC2D, OCIL)-NKRP1A (CD161) interaction enhances natural killer cell-mediated lysis of triple-negative breast cancer cells.Am J Cancer Res. 2018 Jun 1;8(6):1050-1063. eCollection 2018.
21 Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals.Front Immunol. 2017 Aug 10;8:968. doi: 10.3389/fimmu.2017.00968. eCollection 2017.
22 How does variability of immune system genes affect placentation?.Placenta. 2011 Aug;32(8):539-45. doi: 10.1016/j.placenta.2011.05.001. Epub 2011 Jun 12.
23 Circulating CD3(+)CD4(+)CD161(+) Cells Are Associated with Early Complications after Autologous Stem Cell Transplantation in Multiple Myeloma.Biomed Res Int. 2018 Jan 1;2018:5097325. doi: 10.1155/2018/5097325. eCollection 2018.
24 TCR gamma delta+ and CD161+ thymocytes express HIV-1 in the SCID-hu mouse, potentially contributing to immune dysfunction in HIV infection.J Immunol. 2002 Nov 1;169(9):5338-46. doi: 10.4049/jimmunol.169.9.5338.
25 Aberrant expression of NK cell receptors in Epstein-Barr virus-positive gammadelta T-cell lymphoproliferative disorders.Hematology. 2010 Feb;15(1):43-7. doi: 10.1179/102453310X12583347009450.
26 Altered phosphorylated signal transducer and activator of transcription profile of CD4+CD161+ T cells in asthma: modulation by allergic status and oral corticosteroids.J Allergy Clin Immunol. 2007 Dec;120(6):1441-8. doi: 10.1016/j.jaci.2007.08.012. Epub 2007 Oct 24.
27 Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an ex-vivo assay for Th17 deficiency of diagnostic utility.Clin Exp Immunol. 2016 May;184(2):216-27. doi: 10.1111/cei.12746. Epub 2016 Feb 9.
28 Association Between Impaired V7.2+CD161++CD8+ (MAIT) and V7.2+CD161-CD8+ T-Cell Populations and Gut Dysbiosis in Chronically HIV- and/or HCV-Infected Patients.Front Microbiol. 2019 Aug 28;10:1972. doi: 10.3389/fmicb.2019.01972. eCollection 2019.
29 Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions.World J Gastroenterol. 2018 Mar 21;24(11):1228-1238. doi: 10.3748/wjg.v24.i11.1228.
30 CD161 Defines a Functionally Distinct Subset of Pro-Inflammatory Natural Killer Cells.Front Immunol. 2018 Apr 9;9:486. doi: 10.3389/fimmu.2018.00486. eCollection 2018.
31 Chronic inflammation during osteoarthritis is associated with an increased expression of CD161 during advanced stage.Scand J Immunol. 2019 Jul;90(1):e12770. doi: 10.1111/sji.12770. Epub 2019 May 14.
32 Interleukin-17-producing Tcells and interleukin-17 mRNA expression in periodontitis and long-standing gingivitis lesions.J Periodontol. 2019 May;90(5):516-521. doi: 10.1002/JPER.18-0326. Epub 2019 Jan 8.
33 Effectiveness of two different dose administration regimens of an IL-15 superagonist complex (ALT-803) in an orthotopic bladder cancer mouse model.J Transl Med. 2019 Jan 17;17(1):29. doi: 10.1186/s12967-019-1778-6.
34 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
35 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
36 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
37 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.