Details of Drug Off-Target (DOT)

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

• DOT Name: SH2 domain-containing protein 3A (SH2D3A)
• Synonyms: Novel SH2-containing protein 1
• Gene Name: SH2D3A
• Related Disease:
  Alphavirus infectious disease
  Arthritis
  Breast neoplasm
  Diarrhea
  Frontonasal dysplasia
  Severe acute respiratory syndrome (SARS)
  Chikungunya virus infection
  Intellectual disability
  Leber congenital amaurosis 1
  Middle East Respiratory Syndrome (MERS)
• UniProt ID: SH23A_HUMAN
• Pfam ID: PF00017
• Sequence:
  MQVPQDGEDLAGQPWYHGLLSRQKAEALLQQNGDFLVRASGSRGGNPVISCRWRGSALHF
  EVFRVALRPRPGRPTALFQLEDEQFPSIPALVHSYMTGRRPLSQATGAVVSRPVTWQGPL
  RRSFSEDTLMDGPARIEPLRARKWSNSQPADLAHMGRSREDPAGMEASTMPISALPRTSS
  DPVLLKAPAPLGTVADSLRASDGQLQAKAPTKPPRTPSFELPDASERPPTYCELVPRVPS
  VQGTSPSQSCPEPEAPWWEAEEDEEEENRCFTRPQAEISFCPHDAPSCLLGPQNRPLEPQ
  VLHTLRGLFLEHHPGSTALHLLLVDCQATGLLGVTRDQRGNMGVSSGLELLTLPHGHHLR
  LELLERHQTLALAGALAVLGCSGPLEERAAALRGLVELALALRPGAAGDLPGLAAVMGAL
  LMPQVSRLEHTWRQLRRSHTEAALAFEQELKPLMRALDEGAGPCDPGEVALPHVAPMVRL
  LEGEEVAGPLDESCERLLRTLHGARHMVRDAPKFRKVAAQRLRGFRPNPELREALTTGFV
  RRLLWGSRGAGAPRAERFEKFQRVLGVLSQRLEPDR
• Function: May play a role in JNK activation.
• Tissue Specificity: Weakly expressed in placenta, fetal kidney, fetal lung, adult pancreas, adult kidney and adult lung.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alphavirus infectious disease	DISZGSCJ	Definitive	Biomarker	[1]
Arthritis	DIST1YEL	Definitive	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Diarrhea	DISWTJQL	Strong	Biomarker	[4]
Frontonasal dysplasia	DISXV4YX	Strong	Genetic Variation	[5]
Severe acute respiratory syndrome (SARS)	DISYW14W	Strong	Biomarker	[6]
Chikungunya virus infection	DISDXEHY	Limited	Altered Expression	[7]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[8]
Leber congenital amaurosis 1	DISY2B33	Limited	Biomarker	[9]
Middle East Respiratory Syndrome (MERS)	DIS5VPYU	Limited	Biomarker	[10]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	SH2 domain-containing protein 3A (SH2D3A) decreases the response to substance of Arsenic trioxide.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of SH2 domain-containing protein 3A (SH2D3A).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH2 domain-containing protein 3A (SH2D3A).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SH2 domain-containing protein 3A (SH2D3A).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SH2 domain-containing protein 3A (SH2D3A).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of SH2 domain-containing protein 3A (SH2D3A).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of SH2 domain-containing protein 3A (SH2D3A).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SH2 domain-containing protein 3A (SH2D3A).	[18]

4 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 decreases the methylation of SH2 domain-containing protein 3A (SH2D3A).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SH2 domain-containing protein 3A (SH2D3A).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SH2 domain-containing protein 3A (SH2D3A).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of SH2 domain-containing protein 3A (SH2D3A).	[19]

References

• [1] Inflammatory monocytes mediate control of acute alphavirus infection in mice.PLoS Pathog. 2017 Dec 15;13(12):e1006748. doi: 10.1371/journal.ppat.1006748. eCollection 2017 Dec.
• [2] Fingolimod treatment abrogates chikungunya virus-induced arthralgia.Sci Transl Med. 2017 Feb 1;9(375):eaal1333. doi: 10.1126/scitranslmed.aal1333.
• [3] AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology.J Cell Physiol. 2007 Sep;212(3):655-65. doi: 10.1002/jcp.21059.
• [4] Rotavirus Species B Encodes a Functional Fusion-Associated Small Transmembrane Protein.J Virol. 2019 Sep 30;93(20):e00813-19. doi: 10.1128/JVI.00813-19. Print 2019 Oct 15.
• [5] Exome sequencing revealed a novel nonsense variant in ALX3 gene underlying frontorhiny.J Hum Genet. 2018 Jan;63(1):97-100. doi: 10.1038/s10038-017-0358-y. Epub 2017 Nov 16.
• [6] SARS coronavirus protein nsp1 disrupts localization of Nup93 from the nuclear pore complex.Biochem Cell Biol. 2019 Dec;97(6):758-766. doi: 10.1139/bcb-2018-0394. Epub 2019 Apr 3.
• [7] Inhibition of Chikungunya virus by an adenosine analog targeting the SAM-dependent nsP1 methyltransferase.FEBS Lett. 2020 Feb;594(4):678-694. doi: 10.1002/1873-3468.13642. Epub 2019 Nov 2.
• [8] A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability.BMC Med Genet. 2011 Apr 22;12:56. doi: 10.1186/1471-2350-12-56.
• [9] Homozygosity mapping guided next generation sequencing to identify the causative genetic variation in inherited retinal degenerative diseases.J Hum Genet. 2016 Nov;61(11):951-958. doi: 10.1038/jhg.2016.83. Epub 2016 Jul 7.
• [10] The Endonucleolytic RNA Cleavage Function of nsp1 of Middle East Respiratory Syndrome Coronavirus Promotes the Production of Infectious Virus Particles in Specific Human Cell Lines.J Virol. 2018 Oct 12;92(21):e01157-18. doi: 10.1128/JVI.01157-18. Print 2018 Nov 1.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] 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.
• [18] 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.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.