Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTORRCG6)

DOT Name Protein-glutamine gamma-glutamyltransferase 4 (TGM4)
Synonyms EC 2.3.2.13; Fibrinoligase; Prostate transglutaminase; Prostate-specific transglutaminase; Transglutaminase P; TG(P); TGP; TGase P; Transglutaminase-4; TGase-4
Gene Name TGM4
Related Disease
Benign prostatic hyperplasia ( )
Metastatic prostate carcinoma ( )
Prostate neoplasm ( )
Periodontitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
TGM4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.13
Pfam ID
PF00927 ; PF01841 ; PF00868
Sequence
MMDASKELQVLHIDFLNQDNAVSHHTWEFQTSSPVFRRGQVFHLRLVLNQPLQSYHQLKL
EFSTGPNPSIAKHTLVVLDPRTPSDHYNWQATLQNESGKEVTVAVTSSPNAILGKYQLNV
KTGNHILKSEENILYLLFNPWCKEDMVFMPDEDERKEYILNDTGCHYVGAARSIKCKPWN
FGQFEKNVLDCCISLLTESSLKPTDRRDPVLVCRAMCAMMSFEKGQGVLIGNWTGDYEGG
TAPYKWTGSAPILQQYYNTKQAVCFGQCWVFAGILTTVLRALGIPARSVTGFDSAHDTER
NLTVDTYVNENGEKITSMTHDSVWNFHVWTDAWMKRPDLPKGYDGWQAVDATPQERSQGV
FCCGPSPLTAIRKGDIFIVYDTRFVFSEVNGDRLIWLVKMVNGQEELHVISMETTSIGKN
ISTKAVGQDRRRDITYEYKYPEGSSEERQVMDHAFLLLSSEREHRRPVKENFLHMSVQSD
DVLLGNSVNFTVILKRKTAALQNVNILGSFELQLYTGKKMAKLCDLNKTSQIQGQVSEVT
LTLDSKTYINSLAILDDEPVIRGFIIAEIVESKEIMASEVFTSFQYPEFSIELPNTGRIG
QLLVCNCIFKNTLAIPLTDVKFSLESLGISSLQTSDHGTVQPGETIQSQIKCTPIKTGPK
KFIVKLSSKQVKEINAQKIVLITK
Function Associated with the mammalian reproductive process. Catalyzes the cross-linking of proteins and the conjugation of polyamines to specific proteins in the seminal tract.
Tissue Specificity Prostate.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Benign prostatic hyperplasia DISI3CW2 Strong Altered Expression [1]
Metastatic prostate carcinoma DISVBEZ9 Strong Altered Expression [2]
Prostate neoplasm DISHDKGQ Strong Altered Expression [1]
Periodontitis DISI9JOI moderate Genetic Variation [3]
Prostate cancer DISF190Y Limited Biomarker [4]
Prostate carcinoma DISMJPLE Limited Biomarker [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [9]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin affects the expression of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [6]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [7]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [7]
Beta-carotene DM0RXBT Approved Beta-carotene increases the expression of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [8]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Protein-glutamine gamma-glutamyltransferase 4 (TGM4). [10]
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References

1 Molecular analyses of prostate tumors for diagnosis of malignancy on fine-needle aspiration biopsies.Oncotarget. 2017 Nov 6;8(62):104761-104771. doi: 10.18632/oncotarget.22289. eCollection 2017 Dec 1.
2 Human prostate-specific transglutaminase gene: promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer.Urology. 1999 Dec;54(6):1105-11. doi: 10.1016/s0090-4295(99)00298-8.
3 IL1 gene polymorphisms and unsuccessful dental implants.Clin Oral Implants Res. 2012 Dec;23(12):1404-13. doi: 10.1111/j.1600-0501.2011.02322.x. Epub 2011 Nov 10.
4 Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients.Mol Cell Proteomics. 2019 Sep;18(9):1807-1823. doi: 10.1074/mcp.RA119.001612. Epub 2019 Jun 27.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
7 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
8 Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
9 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.
10 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.