Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQTO5QZ)

DOT Name	Pre T-cell antigen receptor alpha (PTCRA)
Synonyms	pT-alpha; pTa; pT-alpha-TCR
Gene Name	PTCRA
Related Disease	Endolymphatic hydrops ( ) Advanced cancer ( ) Alzheimer disease ( ) Cardiovascular disease ( ) Deafness ( ) Huntington disease ( ) Neoplasm ( ) Peripheral arterial disease ( ) Persistent truncus arteriosus ( ) Polycystic ovarian syndrome ( ) Promyelocytic leukaemia ( ) Sensorineural hearing loss disorder ( ) T-cell leukaemia ( ) Hepatitis B virus infection ( ) Methicillin-resistant staphylococci infection ( ) Pendred syndrome ( ) Stroke ( ) Dementia ( ) Frontotemporal dementia ( ) Lewy body dementia ( ) Migraine disorder ( ) Osteoarthritis ( ) Pick disease ( ) Type-1/2 diabetes ( ) Vascular dementia ( )
UniProt ID	PTCRA_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3OF6
Pfam ID	PF15028
Sequence	MAGTWLLLLLALGCPALPTGVGGTPFPSLAPPIMLLVDGKQQMVVVCLVLDVAPPGLDSP IWFSAGNGSALDAFTYGPSPATDGTWTNLAHLSLPSEELASWEPLVCHTGPGAEGHSRST QPMHLSGEASTARTCPQEPLRGTPGGALWLGVLRLLLFKLLLFDLLLTCSCLCDPAGPLP SPATTTRLRALGSHRLHPATETGGREATSSPRPQPRDRRWGDTPPGRKPGSPVWGEGSYL SSYPTCPAQAWCSRSALRAPSSSLGAFFAGDLPPPLQAGAA
Function	The pre-T-cell receptor complex (composed of PTCRA, TCRB and the CD3 complex) regulates early T-cell development.
Tissue Specificity	Expressed in immature but not mature T-cells. Also found in CD34+ cells from peripheral blood, CD34+ precursors from umbilical cord blood and adult bone marrow.
KEGG Pathway	Notch sig.ling pathway (hsa04330 ) Transcriptio.l misregulation in cancer (hsa05202 )
Reactome Pathway	NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508 )

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Endolymphatic hydrops	DISUPJBC	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Deafness	DISKCLH4	Strong	Biomarker	[5]
Huntington disease	DISQPLA4	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Peripheral arterial disease	DIS78WFB	Strong	Biomarker	[8]
Persistent truncus arteriosus	DISRZ8EA	Strong	Biomarker	[9]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[10]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[11]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[12]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[13]
Hepatitis B virus infection	DISLQ2XY	moderate	Biomarker	[14]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[15]
Pendred syndrome	DISZ1MU8	moderate	Genetic Variation	[16]
Stroke	DISX6UHX	moderate	Biomarker	[17]
Dementia	DISXL1WY	Limited	Biomarker	[18]
Frontotemporal dementia	DISKYHXL	Limited	Biomarker	[18]
Lewy body dementia	DISAE66J	Limited	Biomarker	[18]
Migraine disorder	DISFCQTG	Limited	Biomarker	[19]
Osteoarthritis	DIS05URM	Limited	Biomarker	[20]
Pick disease	DISP6X50	Limited	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[21]
Vascular dementia	DISVO82H	Limited	Biomarker	[18]
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⏷ Show the Full List of 25 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Pre T-cell antigen receptor alpha (PTCRA).	[22]
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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 decreases the methylation of Pre T-cell antigen receptor alpha (PTCRA).	[23]
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References

1	Quantitative evaluation of endolymphatic hydrops with MRI through intravenous gadolinium administration and VEMP in unilateral definite Meniere's disease.Eur Arch Otorhinolaryngol. 2019 Apr;276(4):993-1000. doi: 10.1007/s00405-018-05267-7. Epub 2019 Jan 29.
2	New Class of Half-Sandwich Ruthenium(II) Arene Complexes Bearing the Water-Soluble CAP Ligand as an in Vitro Anticancer Agent.Inorg Chem. 2017 May 15;56(10):5514-5518. doi: 10.1021/acs.inorgchem.7b00915. Epub 2017 Apr 26.
3	Role of PTA in the prevention of Cu(amyloid-) induced ROS formation and amyloid- oligomerisation in the presence of Zn.Metallomics. 2019 Jun 19;11(6):1154-1161. doi: 10.1039/c9mt00011a.
4	3D MicroCT spatial and temporal characterization of thoracic aorta perivascular adipose tissue and plaque volumes in the ApoE-/- mouse model.Adipocyte. 2018;7(3):156-165. doi: 10.1080/21623945.2018.1493900. Epub 2018 Aug 9.
5	The impact of permanent early-onset unilateral hearing impairment in children - A systematic review.Int J Pediatr Otorhinolaryngol. 2019 May;120:173-183. doi: 10.1016/j.ijporl.2019.02.029. Epub 2019 Feb 19.
6	Dysregulated brain creatine kinase is associated with hearing impairment in mouse models of Huntington disease.J Clin Invest. 2011 Apr;121(4):1519-23. doi: 10.1172/JCI43220. Epub 2011 Mar 14.
7	Audiologic Natural History of Small Volume Cochleovestibular Schwannomas in Neurofibromatosis Type 2.Otol Neurotol. 2018 Mar;39(3):357-364. doi: 10.1097/MAO.0000000000001690.
8	Trends in Lower Limb Amputation in Patients with Diabetic Foot Based on Vascular Intervention of Peripheral Arterial Disease in Korea: a Population-based Nationwide Study.J Korean Med Sci. 2019 Jul 8;34(26):e178. doi: 10.3346/jkms.2019.34.e178.
9	Anatomical evaluation of the vertebral artery (V2) and its influence in cervical spine surgery.Clin Neurol Neurosurg. 2018 Nov;174:80-85. doi: 10.1016/j.clineuro.2018.09.002. Epub 2018 Sep 8.
10	Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
11	Expression of T-lineage-affiliated transcripts and TCR rearrangements in acute promyelocytic leukemia: implications for the cellular target of t(15;17).Blood. 2006 Nov 15;108(10):3484-93. doi: 10.1182/blood-2005-09-009977. Epub 2006 Jul 20.
12	Main Aspects of Peripheral and Central Hearing System Involvement in Unexplained HIV-Related Hearing Complaints.Front Neurol. 2019 Aug 6;10:845. doi: 10.3389/fneur.2019.00845. eCollection 2019.
13	Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis.Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3788-93. doi: 10.1073/pnas.062050599. Epub 2002 Mar 12.
14	Correlation of TLR1-10 expression in peripheral blood mononuclear cells with chronic hepatitis B and chronic hepatitis B-related liver failure.Hum Immunol. 2010 Oct;71(10):950-6. doi: 10.1016/j.humimm.2010.07.013. Epub 2010 Jul 24.
15	How Much Vancomycin Dose Is Enough For The MRSA Infection in Pediatric Patients With Various Degrees of Renal Function?.Iran J Pharm Res. 2019 Spring;18(2):995-1009. doi: 10.22037/ijpr.2019.1100654.
16	A pathogenic variant in SLC26A4 is associated with Pendred syndrome in a consanguineous Iranian family.Int J Audiol. 2019 Oct;58(10):628-634. doi: 10.1080/14992027.2019.1619945. Epub 2019 Jun 12.
17	In-Hospital Cardiovascular Complications After Pancreas Transplantation in the United States from 2003 to 2012.Am J Cardiol. 2017 Aug 15;120(4):682-687. doi: 10.1016/j.amjcard.2017.05.038. Epub 2017 May 30.
18	Midregional Proenkephalin A and N-terminal Protachykinin A are decreased in the cerebrospinal fluid of patients with dementia disorders and acute neuroinflammation.J Neuroimmunol. 2010 Apr 15;221(1-2):62-7. doi: 10.1016/j.jneuroim.2010.02.004. Epub 2010 Mar 5.
19	Endolymphatic hydrops in idiopathic intracranial hypertension: prevalence and clinical outcome after lumbar puncture. Preliminary data.Neurol Sci. 2017 May;38(Suppl 1):193-196. doi: 10.1007/s10072-017-2895-8.
20	Sr/PTA Metal Organic Framework as A Drug Delivery System for Osteoarthritis Treatment.Sci Rep. 2019 Nov 26;9(1):17570. doi: 10.1038/s41598-019-54147-5.
21	Impact of Inherited Prothrombotic Disorders on the Long-Term Clinical Outcome of Percutaneous Transluminal Angioplasty in Patients with Diabetes.J Diabetes Res. 2015;2015:369758. doi: 10.1155/2015/369758. Epub 2015 Jul 13.
22	Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
23	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.