Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4D5EG7)

• DOT Name: T-cell surface glycoprotein CD1b (CD1B)
• Synonyms: CD antigen CD1b
• Gene Name: CD1B
• Related Disease:
  Adrenoleukodystrophy
  Bacterial infection
  Dermatitis
  Hyperlipidemia
  Lyme disease
  Mycobacterium infection
  Psoriasis
  Tuberculosis
  Advanced cancer
  Granular corneal dystrophy type II
  Latent tuberculosis infection
  Lysosomal storage disease
  Malaria
  Multiple sclerosis
  Neoplasm
  Sickle-cell anaemia
  Thalassemia
• UniProt ID: CD1B_HUMAN
• PDB ID: 1GZP; 1GZQ; 1UQS; 2H26; 3OV6; 3T8X; 4ONO; 5C9J; 5L2J; 5L2K; 5WKE; 5WKG; 5WKI; 5WL1; 6CUG; 6D64; 8DV3; 8DV4; 8GLE; 8GLF; 8GLG; 8GLH; 8GLI
• Pfam ID: PF07654 ; PF16497
• Sequence:
  MLLLPFQLLAVLFPGGNSEHAFQGPTSFHVIQTSSFTNSTWAQTQGSGWLDDLQIHGWDS
  DSGTAIFLKPWSKGNFSDKEVAELEEIFRVYIFGFAREVQDFAGDFQMKYPFEIQGIAGC
  ELHSGGAIVSFLRGALGGLDFLSVKNASCVPSPEGGSRAQKFCALIIQYQGIMETVRILL
  YETCPRYLLGVLNAGKADLQRQVKPEAWLSSGPSPGPGRLQLVCHVSGFYPKPVWVMWMR
  GEQEQQGTQLGDILPNANWTWYLRATLDVADGEAAGLSCRVKHSSLEGQDIILYWRNPTS
  IGSIVLAIIVPSLLLLLCLALWYMRRRSYQNIP
• Function: Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.
• Tissue Specificity: Expressed on cortical thymocytes, on certain T-cell leukemias, and in various other tissues.
• KEGG Pathway:
  Tight junction (hsa04530)
  Hematopoietic cell lineage (hsa04640)
  Amoebiasis (hsa05146)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adrenoleukodystrophy	DISTUD1F	Strong	Genetic Variation	[1]
Bacterial infection	DIS5QJ9S	Strong	Genetic Variation	[2]
Dermatitis	DISY5SZC	Strong	Biomarker	[3]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[3]
Lyme disease	DISO70G5	Strong	Biomarker	[4]
Mycobacterium infection	DISNSMUD	Strong	Biomarker	[5]
Psoriasis	DIS59VMN	Strong	Biomarker	[6]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[8]
Granular corneal dystrophy type II	DISAEE20	Limited	Genetic Variation	[9]
Latent tuberculosis infection	DIS6R1EH	Limited	Genetic Variation	[10]
Lysosomal storage disease	DIS6QM6U	Limited	Biomarker	[11]
Malaria	DISQ9Y50	Limited	Biomarker	[12]
Multiple sclerosis	DISB2WZI	Limited	Altered Expression	[13]
Neoplasm	DISZKGEW	Limited	Biomarker	[14]
Sickle-cell anaemia	DIS5YNZB	Limited	Altered Expression	[15]
Thalassemia	DIS76XZB	Limited	Altered Expression	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of T-cell surface glycoprotein CD1b (CD1B).	[16]

References

• [1] CD1 gene polymorphisms and phenotypic variability in X-linked adrenoleukodystrophy.PLoS One. 2012;7(1):e29872. doi: 10.1371/journal.pone.0029872. Epub 2012 Jan 12.
• [2] Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells.Immunity. 2002 May;16(5):697-706. doi: 10.1016/s1074-7613(02)00311-4.
• [3] CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice.J Clin Invest. 2017 Jun 1;127(6):2339-2352. doi: 10.1172/JCI92217. Epub 2017 May 2.
• [4] CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells.Eur J Immunol. 2019 May;49(5):737-746. doi: 10.1002/eji.201847949. Epub 2019 Mar 20.
• [5] Validation of a CD1b tetramer assay for studies of human mycobacterial infection or vaccination.J Immunol Methods. 2018 Jul;458:44-52. doi: 10.1016/j.jim.2018.04.004. Epub 2018 Apr 21.
• [6] A molecular basis of human T cell receptor autoreactivity toward self-phospholipids.Sci Immunol. 2017 Oct 20;2(16):eaao1384. doi: 10.1126/sciimmunol.aao1384.
• [7] Interactions of domain antibody (dAb11) with Mycobacterium tuberculosis Ac(2)SGL in complex with CD1b.Tuberculosis (Edinb). 2019 Jan;114:9-16. doi: 10.1016/j.tube.2018.11.002. Epub 2018 Nov 4.
• [8] The intricacies of self-lipid antigen presentation by CD1b.Mol Immunol. 2018 Dec;104:27-36. doi: 10.1016/j.molimm.2018.09.022. Epub 2018 Nov 3.
• [9] Development of a DNA chip for the diagnosis of the most common corneal dystrophies caused by mutations in the betaigh3 gene.Br J Ophthalmol. 2007 Jun;91(6):722-7. doi: 10.1136/bjo.2006.111070. Epub 2007 Jan 10.
• [10] Phage display of functional single-chain T-cell receptor molecules specific for CD1b:AcSGL complexes from Mycobacterium tuberculosis-infected cells.BMC Immunol. 2013;14 Suppl 1(Suppl 1):S2. doi: 10.1186/1471-2172-14-S1-S2. Epub 2013 Feb 25.
• [11] Lipid Antigen Presentation by CD1b and CD1d in Lysosomal Storage Disease Patients.Front Immunol. 2019 Jun 4;10:1264. doi: 10.3389/fimmu.2019.01264. eCollection 2019.
• [12] Identifying and structurally characterizing CD1b in Aotus nancymaae owl monkeys.Immunogenetics. 2004 Oct;56(7):480-9. doi: 10.1007/s00251-004-0716-8. Epub 2004 Sep 10.
• [13] CD1b is expressed in multiple sclerosis lesions.J Neuroimmunol. 1996 Jul;67(2):145-51. doi: 10.1016/0165-5728(96)00045-8.
• [14] Cyclin D1 gene amplification and p16 gene deletion in patients with esophageal carcinosarcoma.Diagn Mol Pathol. 1998 Oct;7(5):253-9. doi: 10.1097/00019606-199810000-00004.
• [15] Upregulation and atypical expression of the CD1 molecules on monocytes in sickle cell disease.Hum Immunol. 2004 Nov;65(11):1370-6. doi: 10.1016/j.humimm.2004.09.009.
• [16] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.