Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6KOR77)

• DOT Name: Receptor-type tyrosine-protein phosphatase C (PTPRC)
• Synonyms: EC 3.1.3.48; Leukocyte common antigen; L-CA; T200; CD antigen CD45
• Gene Name: PTPRC
• Related Disease:
  Immunodeficiency 104
  T-B+ severe combined immunodeficiency due to CD45 deficiency
• UniProt ID: PTPRC_HUMAN
• PDB ID: 1YGR; 1YGU; 5FMV; 5FN6; 5FN7
• EC Number: 3.1.3.48
• Pfam ID: PF12567 ; PF00041 ; PF12453 ; PF00102
• Sequence:
  MTMYLWLKLLAFGFAFLDTEVFVTGQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPA
  STFERENDFSETTTSLSPDNTSTQVSPDSLDNASAFNTTGVSSVQTPHLPTHADSQTPSA
  GTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTASTFPTDPVSPLTTTLSLAHHSSAAL
  PARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTPSKPTCDEKYANITVDYL
  YNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAPDKTLILDVP
  PGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENLE
  PEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFH
  NFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTT
  KSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFR
  VKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKALIAFLAFLIIVTSIALLVVLYK
  IYDLHKKRSCNLDEQQELVERDDEKQLMNVEPIHADILLETYKRKIADEGRLFLAEFQSI
  PRVFSKFPIKEARKPFNQNKNRYVDILPYDYNRVELSEINGDAGSNYINASYIDGFKEPR
  KYIAAQGPRDETVDDFWRMIWEQKATVIVMVTRCEEGNRNKCAEYWPSMEEGTRAFGDVV
  VKINQHKRCPDYIIQKLNIVNKKEKATGREVTHIQFTSWPDHGVPEDPHLLLKLRRRVNA
  FSNFFSGPIVVHCSAGVGRTGTYIGIDAMLEGLEAENKVDVYGYVVKLRRQRCLMVQVEA
  QYILIHQALVEYNQFGETEVNLSELHPYLHNMKKRDPPSEPSPLEAEFQRLPSYRSWRTQ
  HIGNQEENKSKNRNSNVIPYDYNRVPLKHELEMSKESEHDSDESSDDDSDSEEPSKYINA
  SFIMSYWKPEVMIAAQGPLKETIGDFWQMIFQRKVKVIVMLTELKHGDQEICAQYWGEGK
  QTYGDIEVDLKDTDKSSTYTLRVFELRHSKRKDSRTVYQYQYTNWSVEQLPAEPKELISM
  IQVVKQKLPQKNSSEGNKHHKSTPLLIHCRDGSQQTGIFCALLNLLESAETEEVVDIFQV
  VKALRKARPGMVSTFEQYQFLYDVIASTYPAQNGQVKKNNHQEDKIEFDNEVDKVKQDAN
  CVNPLGAPEKLPEAKEQAEGSEPTSGTEGPEHSVNGPASPALNQGS
• Function: Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity; (Microbial infection) Acts as a receptor for human cytomegalovirus protein UL11 and mediates binding of UL11 to T-cells, leading to reduced induction of tyrosine phosphorylation of multiple signaling proteins upon T-cell receptor stimulation and impaired T-cell proliferation.
• Tissue Specificity: Isoform 1: Detected in thymocytes. Isoform 2: Detected in thymocytes. Isoform 3: Detected in thymocytes. Isoform 4: Not detected in thymocytes. Isoform 5: Detected in thymocytes. Isoform 6: Not detected in thymocytes. Isoform 7: Detected in thymocytes. Isoform 8: Not detected in thymocytes.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  T cell receptor sig.ling pathway (hsa04660)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Salmonella infection (hsa05132)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Other semaphorin interactions (R-HSA-416700)
  Neutrophil degranulation (R-HSA-6798695)
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency 104	DISJFQSY	Definitive	Autosomal recessive	[1]
T-B+ severe combined immunodeficiency due to CD45 deficiency	DISTV4ZP	Supportive	Autosomal recessive	[2]

18 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 Receptor-type tyrosine-protein phosphatase C (PTPRC).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone affects the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[11]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[12]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[13]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[15]
Tesmilifene	DMPB36I	Discontinued in Phase 2	Tesmilifene decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[16]
D-7193	DMO9HWU	Discontinued in Phase 2	D-7193 affects the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[18]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[19]
Cordycepin	DM72Y01	Investigative	Cordycepin affects the expression of Receptor-type tyrosine-protein phosphatase C (PTPRC).	[20]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] A deletion in the gene encoding the CD45 antigen in a patient with SCID. J Immunol. 2001 Jan 15;166(2):1308-13. doi: 10.4049/jimmunol.166.2.1308.
• [3] Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] Sensitivity of leukemic T-cell lines to arsenic trioxide cytotoxicity is dependent on the induction of phosphatase B220/CD45R expression at the cell surface. Mol Cancer. 2014 Nov 19;13:251. doi: 10.1186/1476-4598-13-251.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [9] Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.
• [10] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [13] Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
• [14] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Inhibition of effects of endogenously synthesized histamine disturbs in vitro human dendritic cell differentiation. Immunol Lett. 2001 Apr 2;76(3):175-82. doi: 10.1016/s0165-2478(01)00184-5.
• [17] The new oral immunomodulating drug DiNAC induces brachial artery vasodilatation at rest and during hyperemia in hypercholesterolemic subjects, likely by a nitric oxide-dependent mechanism. Atherosclerosis. 2008 Jan;196(1):275-282. doi: 10.1016/j.atherosclerosis.2006.10.031. Epub 2006 Dec 8.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [20] Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells. Eur J Pharmacol. 2002 Oct 25;453(2-3):309-17. doi: 10.1016/s0014-2999(02)02359-2.