Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4QX6BR)

• DOT Name: Immunoglobulin superfamily member 2 (CD101)
• Synonyms: IgSF2; Cell surface glycoprotein V7; Glu-Trp-Ile EWI motif-containing protein 101; EWI-101; CD antigen CD101
• Gene Name: CD101
• Related Disease:
  Candidemia
  Candidiasis, invasive
  Colitis
  Inflammatory bowel disease
  Invasive candidiasis
  Matthew-Wood syndrome
  Pancreatic cancer
  Vulvovaginal Candidiasis
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: IGSF2_HUMAN
• Pfam ID: PF07686
• Sequence:
  MAGISYVASFFLLLTKLSIGQREVTVQKGPLFRAEGYPVSIGCNVTGHQGPSEQHFQWSV
  YLPTNPTQEVQIISTKDAAFSYAVYTQRVRSGDVYVERVQGNSVLLHISKLQMKDAGEYE
  CHTPNTDEKYYGSYSAKTNLIVIPDTLSATMSSQTLGKEEGEPLALTCEASKATAQHTHL
  SVTWYLTQDGGGSQATEIISLSKDFILVPGPLYTERFAASDVQLNKLGPTTFRLSIERLQ
  SSDQGQLFCEATEWIQDPDETWMFITKKQTDQTTLRIQPAVKDFQVNITADSLFAEGKPL
  ELVCLVVSSGRDPQLQGIWFFNGTEIAHIDAGGVLGLKNDYKERASQGELQVSKLGPKAF
  SLKIFSLGPEDEGAYRCVVAEVMKTRTGSWQVLQRKQSPDSHVHLRKPAARSVVMSTKNK
  QQVVWEGETLAFLCKAGGAESPLSVSWWHIPRDQTQPEFVAGMGQDGIVQLGASYGVPSY
  HGNTRLEKMDWATFQLEITFTAITDSGTYECRVSEKSRNQARDLSWTQKISVTVKSLESS
  LQVSLMSRQPQVMLTNTFDLSCVVRAGYSDLKVPLTVTWQFQPASSHIFHQLIRITHNGT
  IEWGNFLSRFQKKTKVSQSLFRSQLLVHDATEEETGVYQCEVEVYDRNSLYNNRPPRASA
  ISHPLRIAVTLPESKLKVNSRSQVQELSINSNTDIECSILSRSNGNLQLAIIWYFSPVST
  NASWLKILEMDQTNVIKTGDEFHTPQRKQKFHTEKVSQDLFQLHILNVEDSDRGKYHCAV
  EEWLLSTNGTWHKLGEKKSGLTELKLKPTGSKVRVSKVYWTENVTEHREVAIRCSLESVG
  SSATLYSVMWYWNRENSGSKLLVHLQHDGLLEYGEEGLRRHLHCYRSSSTDFVLKLHQVE
  MEDAGMYWCRVAEWQLHGHPSKWINQASDESQRMVLTVLPSEPTLPSRICSSAPLLYFLF
  ICPFVLLLLLLISLLCLYWKARKLSTLRSNTRKEKALWVDLKEAGGVTTNRREDEEEDEG
  N
• Function: Plays a role as inhibitor of T-cells proliferation induced by CD3. Inhibits expression of IL2RA on activated T-cells and secretion of IL2. Inhibits tyrosine kinases that are required for IL2 production and cellular proliferation. Inhibits phospholipase C-gamma-1/PLCG1 phosphorylation and subsequent CD3-induced changes in intracellular free calcium. Prevents nuclear translocation of nuclear factor of activated T-cell to the nucleus. Plays a role in the inhibition of T-cell proliferation via IL10 secretion by cutaneous dendritic cells. May be a marker of CD4(+) CD56(+) leukemic tumor cells.
• Tissue Specificity: Expressed in lung, thymus and small intestine. Detected in cutaneous dendritic cells, activated T-cells, monocytes and granulocytes as well as with epithelial cells with dendritic morphology. Expressed in some leukemic cells, the CD4(+) CD56(+) blastic tumor cells, as well as in Langerhans cells from LCH (Langerhans cell histiocytosis) patients.
• Reactome Pathway: Generation of second messenger molecules (R-HSA-202433)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Candidemia	DISVKFN7	Definitive	Biomarker	[1]
Candidiasis, invasive	DIS5VDG3	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[2]
Invasive candidiasis	DIS5EI0L	Strong	Biomarker	[1]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[4]
Vulvovaginal Candidiasis	DISRCR6D	Strong	Biomarker	[5]
Type-1 diabetes	DIS7HLUB	Disputed	Biomarker	[6]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Immunoglobulin superfamily member 2 (CD101).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Immunoglobulin superfamily member 2 (CD101).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Immunoglobulin superfamily member 2 (CD101).	[11]

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 Immunoglobulin superfamily member 2 (CD101).	[10]

References

• [1] Population Pharmacokinetic Analyses for Rezafungin (CD101) Efficacy Using Phase 1 Data.Antimicrob Agents Chemother. 2018 May 25;62(6):e02603-17. doi: 10.1128/AAC.02603-17. Print 2018 Jun.
• [2] CD101 inhibits the expansion of colitogenic T cells.Mucosal Immunol. 2016 Sep;9(5):1205-17. doi: 10.1038/mi.2015.139. Epub 2016 Jan 27.
• [3] Prognostic Values of CD38(+)CD101(+)PD1(+)CD8(+) T Cells in Pancreatic Cancer.Immunol Invest. 2019 Jul;48(5):466-479. doi: 10.1080/08820139.2019.1566356. Epub 2019 Jan 28.
• [4] Inflammation-related gene variants as risk factors for pancreatic cancer.Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1251-4. doi: 10.1158/1055-9965.EPI-11-0264. Epub 2011 Apr 5.
• [5] CD101 Topical Compared With Oral Fluconazole for Acute Vulvovaginal Candidiasis: A Randomized Controlled Trial.J Low Genit Tract Dis. 2019 Jul;23(3):226-229. doi: 10.1097/LGT.0000000000000473.
• [6] Genetic and functional data identifying Cd101 as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice.PLoS Genet. 2019 Jun 14;15(6):e1008178. doi: 10.1371/journal.pgen.1008178. eCollection 2019 Jun.
• [7] Nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility gene in non-obese diabetic mouse, in patients with type 1 diabetes.J Diabetes Investig. 2017 May;8(3):286-294. doi: 10.1111/jdi.12586. Epub 2016 Nov 25.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] 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.
• [11] 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.