Details of Drug Off-Target (DOT)

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

DOT Name	T-cell receptor-associated transmembrane adapter 1 (TRAT1)
Synonyms	T-cell receptor-interacting molecule; TRIM; pp29/30
Gene Name	TRAT1
Related Disease	Alzheimer disease ( ) Arteriosclerosis ( ) Ataxia-telangiectasia ( ) Atherosclerosis ( ) Atopic dermatitis ( ) Bone cancer ( ) Bone osteosarcoma ( ) Brain neoplasm ( ) Breast cancer ( ) Breast carcinoma ( ) Dengue ( ) Glioma ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Herpes simplex infection ( ) Late-onset Parkinson disease ( ) Latent tuberculosis infection ( ) Lung adenocarcinoma ( ) Muscular dystrophy ( ) Neoplasm ( ) Neuroblastoma ( ) Osteosarcoma ( ) Parkinson disease ( ) Periodontal disease ( ) Sjogren syndrome ( ) Tuberculosis ( ) Autoimmune disease ( ) Gastric cancer ( ) Non-small-cell lung cancer ( ) Plasma cell myeloma ( ) Small lymphocytic lymphoma ( ) Stomach cancer ( ) Asthma ( ) Castration-resistant prostate carcinoma ( ) Colorectal carcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Musculoskeletal disorder ( ) Stroke ( )
UniProt ID	TRAT1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF15330
Sequence	MSGISGCPFFLWGLLALLGLALVISLIFNISHYVEKQRQDKMYSYSSDHTRVDEYYIEDT PIYGNLDDMISEPMDENCYEQMKARPEKSVNKMQEATPSAQATNETQMCYASLDHSVKGK RRKPRKQNTHFSDKDGDEQLHAIDASVSKTTLVDSFSPESQAVEENIHDDPIRLFGLIRA KREPIN
Function	Stabilizes the TCR (T-cell antigen receptor)/CD3 complex at the surface of T-cells.
Tissue Specificity	Strongly expressed in thymus, and to a lesser extent in spleen, lymph node and peripheral blood lymphocytes. Present in T-cells and NK cells, but not B-cells (at protein level).
Reactome Pathway	Downstream TCR signaling (R-HSA-202424 ) Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 ) PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 ) PIP3 activates AKT signaling (R-HSA-1257604 )

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[4]
Bone cancer	DIS38NA0	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Dengue	DISKH221	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Altered Expression	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[12]
Late-onset Parkinson disease	DIS9IOUI	Strong	Genetic Variation	[13]
Latent tuberculosis infection	DIS6R1EH	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[18]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[19]
Parkinson disease	DISQVHKL	Strong	Biomarker	[20]
Periodontal disease	DISJQHVN	Strong	Biomarker	[21]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[22]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[14]
Autoimmune disease	DISORMTM	moderate	Biomarker	[23]
Gastric cancer	DISXGOUK	moderate	Biomarker	[24]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[25]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[17]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[17]
Stomach cancer	DISKIJSX	moderate	Biomarker	[24]
Asthma	DISW9QNS	Disputed	Biomarker	[26]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[27]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[28]
Lung cancer	DISCM4YA	Limited	Altered Expression	[29]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[29]
Musculoskeletal disorder	DISPPN0O	Limited	Biomarker	[30]
Stroke	DISX6UHX	Limited	Altered Expression	[31]
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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
Marinol	DM70IK5	Approved	Marinol increases the expression of T-cell receptor-associated transmembrane adapter 1 (TRAT1).	[32]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of T-cell receptor-associated transmembrane adapter 1 (TRAT1).	[33]
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References

1	Increased expression of tripartite motif (TRIM) like 2 promotes tumoral growth in human oral cancer.Biochem Biophys Res Commun. 2019 Jan 22;508(4):1133-1138. doi: 10.1016/j.bbrc.2018.12.060. Epub 2018 Dec 13.
2	Knockdown of TRIM28 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration.Chem Biol Interact. 2019 Sep 25;311:108772. doi: 10.1016/j.cbi.2019.108772. Epub 2019 Jul 24.
3	The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions.Mol Cell Biol. 2010 Jun;30(12):3004-15. doi: 10.1128/MCB.01023-09. Epub 2010 Apr 5.
4	Trim32 Deficiency Enhances Th2 Immunity and Predisposes to Features of Atopic Dermatitis.J Invest Dermatol. 2017 Feb;137(2):359-366. doi: 10.1016/j.jid.2016.09.020. Epub 2016 Oct 5.
5	Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-B signaling pathway.Exp Ther Med. 2018 Mar;15(3):2365-2373. doi: 10.3892/etm.2017.5679. Epub 2017 Dec 27.
6	Crystal structure of the coiled-coil domain of Drosophila TRIM protein Brat.Proteins. 2019 Aug;87(8):706-710. doi: 10.1002/prot.25691. Epub 2019 Apr 19.
7	DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer.PLoS Med. 2009 May 26;6(5):e1000068. doi: 10.1371/journal.pmed.1000068. Epub 2009 May 5.
8	Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3.PLoS Pathog. 2018 Aug 24;14(8):e1007287. doi: 10.1371/journal.ppat.1007287. eCollection 2018 Aug.
9	TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells.J Exp Clin Cancer Res. 2016 Jun 21;35(1):100. doi: 10.1186/s13046-016-0379-y.
10	Interferon alpha (IFN)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.Cell Mol Immunol. 2016 Jan;13(1):94-102. doi: 10.1038/cmi.2014.131. Epub 2015 Feb 16.
11	Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion.Int J Oncol. 2016 Apr;48(4):1639-49. doi: 10.3892/ijo.2016.3398. Epub 2016 Feb 17.
12	TRIM23 mediates virus-induced autophagy via activation of TBK1.Nat Microbiol. 2017 Nov;2(11):1543-1557. doi: 10.1038/s41564-017-0017-2. Epub 2017 Sep 4.
13	The Transcriptional Changes of trim Genes Associated with Parkinson's Disease on a Model of Human Induced Pluripotent Stem Cells.Mol Neurobiol. 2017 Nov;54(9):7204-7211. doi: 10.1007/s12035-016-0230-7. Epub 2016 Oct 29.
14	Gene expression profiling of the TRIM protein family reveals potential biomarkers for indicating tuberculosis status.Microb Pathog. 2018 Jan;114:385-392. doi: 10.1016/j.micpath.2017.12.008. Epub 2017 Dec 7.
15	TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration.Cerebellum. 2019 Apr;18(2):245-254. doi: 10.1007/s12311-018-0987-5.
16	TRIM proteins in therapeutic membrane repair of muscular dystrophy.JAMA Neurol. 2013 Jul;70(7):928-31. doi: 10.1001/jamaneurol.2013.469.
17	TRIM13 inhibited cell proliferation and induced cell apoptosis by regulating NF-B pathway in non-small-cell lung carcinoma cells.Gene. 2019 Oct 5;715:144015. doi: 10.1016/j.gene.2019.144015. Epub 2019 Jul 26.
18	TRIM proteins in neuroblastoma.Biosci Rep. 2019 Dec 20;39(12):BSR20192050. doi: 10.1042/BSR20192050.
19	Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-B signaling pathway.Tumour Biol. 2017 Jun;39(6):1010428317705572. doi: 10.1177/1010428317705572.
20	Silencing of TRIM10 alleviates apoptosis in cellular model of Parkinson's disease.Biochem Biophys Res Commun. 2019 Oct 20;518(3):451-458. doi: 10.1016/j.bbrc.2019.08.041. Epub 2019 Aug 28.
21	Differential expression of inflammasome regulatory transcripts in periodontal disease.J Periodontol. 2020 May;91(5):606-616. doi: 10.1002/JPER.19-0222. Epub 2019 Oct 17.
22	Autoantibodies against the Immunoglobulin-Binding Region of Ro52 Link its Autoantigenicity with Pathogen Neutralization.Sci Rep. 2018 Feb 20;8(1):3345. doi: 10.1038/s41598-018-21522-7.
23	E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2.J Biol Chem. 2019 Jul 26;294(30):11404-11419. doi: 10.1074/jbc.RA119.008485. Epub 2019 Jun 3.
24	Gene expression study and pathway analysis of histological subtypes of intestinal metaplasia that progress to gastric cancer.PLoS One. 2017 Apr 25;12(4):e0176043. doi: 10.1371/journal.pone.0176043. eCollection 2017.
25	Tripartite motif-containing 15 overexpression in non-small cell lung cancer is associated with poor patient prognoses.J Cancer. 2019 Jan 29;10(4):843-852. doi: 10.7150/jca.27856. eCollection 2019.
26	TRIM37 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells.Biomed Pharmacother. 2018 May;101:24-29. doi: 10.1016/j.biopha.2018.02.057. Epub 2018 Feb 22.
27	TRIM-ing Ligand Dependence in Castration-Resistant Prostate Cancer.Cancer Cell. 2016 Jun 13;29(6):776-778. doi: 10.1016/j.ccell.2016.05.014.
28	TRIM47 is up-regulated in colorectal cancer, promoting ubiquitination and degradation of SMAD4.J Exp Clin Cancer Res. 2019 Apr 12;38(1):159. doi: 10.1186/s13046-019-1143-x.
29	High expression of TRIM11 correlates with poor prognosis in patients with hepatocellular carcinoma.Clin Res Hepatol Gastroenterol. 2017 Mar;41(2):190-196. doi: 10.1016/j.clinre.2016.09.010. Epub 2017 Jan 5.
30	Conserved structural and functional aspects of the tripartite motif gene family point towards therapeutic applications in multiple diseases.Pharmacol Ther. 2018 May;185:12-25. doi: 10.1016/j.pharmthera.2017.10.020. Epub 2017 Oct 31.
31	TRIM9-Mediated Resolution of Neuroinflammation Confers Neuroprotection upon Ischemic Stroke in Mice.Cell Rep. 2019 Apr 9;27(2):549-560.e6. doi: 10.1016/j.celrep.2018.12.055.
32	Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
33	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.