Details of Drug Off-Target (DOT)

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

• DOT Name: Signal-regulatory protein beta-1 (SIRPB1)
• Synonyms: SIRP-beta-1; CD172 antigen-like family member B; CD antigen CD172b
• Gene Name: SIRPB1
• Related Disease:
  Alzheimer disease
  Large cell lymphoma
  Neoplasm
  Schizophrenia
• UniProt ID: SIRB1_HUMAN
• PDB ID: 2D9C; 2JJU
• Pfam ID: PF07654 ; PF07686
• Sequence:
  MPVPASWPHLPSPFLLMTLLLGRLTGVAGEDELQVIQPEKSVSVAAGESATLRCAMTSLI
  PVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPADAGTYYC
  VKFRKGSPDDVEFKSGAGTELSVRAKPSAPVVSGPAVRATPEHTVSFTCESHGFSPRDIT
  LKWFKNGNELSDFQTNVDPAGDSVSYSIHSTARVVLTRGDVHSQVICEIAHITLQGDPLR
  GTANLSEAIRVPPTLEVTQQPMRAENQANVTCQVSNFYPRGLQLTWLENGNVSRTETAST
  LIENKDGTYNWMSWLLVNTCAHRDDVVLTCQVEHDGQQAVSKSYALEISAHQKEHGSDIT
  HEAALAPTAPLLVALLLGPKLLLVVGVSAIYICWKQKA
• Function: Immunoglobulin-like cell surface receptor involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. Participates also in the recruitment of tyrosine kinase SYK. Triggers activation of myeloid cells when associated with TYROBP.
• Tissue Specificity: Detected in monocytes and dendritic cells.
• Reactome Pathway:
  Signal regulatory protein family interactions (R-HSA-391160)
  Neutrophil degranulation (R-HSA-6798695)
  DAP12 interactions (R-HSA-2172127)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Large cell lymphoma	DISYZHCP	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	moderate	Altered Expression	[4]

10 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 Signal-regulatory protein beta-1 (SIRPB1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[12]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Signal-regulatory protein beta-1 (SIRPB1).	[15]

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 affects the methylation of Signal-regulatory protein beta-1 (SIRPB1).	[14]

References

• [1] Stem Cell-Derived Neurons as Cellular Models of Sporadic Alzheimer's Disease.J Alzheimers Dis. 2019;67(3):893-910. doi: 10.3233/JAD-180833.
• [2] High-resolution genomic profiling reveals clonal evolution and competition in gastrointestinal marginal zone B-cell lymphoma and its large cell variant.Int J Cancer. 2013 Feb 1;132(3):E116-27. doi: 10.1002/ijc.27774. Epub 2012 Sep 1.
• [3] Read-through transcripts in normal human lung parenchyma are down-regulated in lung adenocarcinoma.Oncotarget. 2016 May 10;7(19):27889-98. doi: 10.18632/oncotarget.8556.
• [4] SIRPB1 copy-number polymorphism as candidate quantitative trait locus for impulsive-disinhibited personality.Genes Brain Behav. 2014 Sep;13(7):653-62. doi: 10.1111/gbb.12154. Epub 2014 Jul 23.
• [5] 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.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [13] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [14] 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.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.