Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0X9WGR)

• DOT Name: POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1)
• Synonyms: BTB/POZ domain zinc finger transcription factor; Protein kinase A RI subunit alpha-associated protein; Zinc finger and BTB domain-containing protein 19; Zinc finger protein 278; Zinc finger sarcoma gene protein
• Gene Name: PATZ1
• Related Disease:
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Adult glioblastoma
  Arteriosclerosis
  Atherosclerosis
  B-cell lymphoma
  Brain neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal neoplasm
  Desmoplastic small round cell tumor
  Differentiated thyroid carcinoma
  Follicular lymphoma
  Glioblastoma multiforme
  Glioma
  Major depressive disorder
  Malignant soft tissue neoplasm
  Neoplasm of testis
  Osteoarthritis
  Sarcoma
  Seminoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Advanced cancer
  Lymphoma
• UniProt ID: PATZ1_HUMAN
• PDB ID: 2EPP; 2EPQ; 2EPR; 2EPS; 2YT9
• Pfam ID: PF00651 ; PF00096 ; PF13912 ; PF16637
• Sequence:
  MERVNDASCGPSGCYTYQVSRHSTEMLHNLNQQRKNGGRFCDVLLRVGDESFPAHRAVLA
  ACSEYFESVFSAQLGDGGAADGGPADVGGATAAPGGGAGGSRELEMHTISSKVFGDILDF
  AYTSRIVVRLESFPELMTAAKFLLMRSVIEICQEVIKQSNVQILVPPARADIMLFRPPGT
  SDLGFPLDMTNGAALAANSNGIAGSMQPEEEAARAAGAAIAGQASLPVLPGVDRLPMVAG
  PLSPQLLTSPFPSVASSAPPLTGKRGRGRPRKANLLDSMFGSPGGLREAGILPCGLCGKV
  FTDANRLRQHEAQHGVTSLQLGYIDLPPPRLGENGLPISEDPDGPRKRSRTRKQVACEIC
  GKIFRDVYHLNRHKLSHSGEKPYSCPVCGLRFKRKDRMSYHVRSHDGSVGKPYICQSCGK
  GFSRPDHLNGHIKQVHTSERPHKCQTCNASFATRDRLRSHLACHEDKVPCQVCGKYLRAA
  YMADHLKKHSEGPSNFCSICNRGFSSASYLKVHVKTHHGVPLPQVSRHQEPILNGGAAFH
  CARTYGNKEGQKCSHQDPIESSDSYGDLSDASDLKTPEKQSANGSFSCDMAVPKNKMESD
  GEKKYPCPECGSFFRSKSYLNKHIQKVHVRALGGPLGDLGPALGSPFSPQQNMSLLESFG
  FQIVQSAFASSLVDPEVDQQPMGPEGK
• Function: Transcriptional regulator that plays a role in many biological processes such as embryogenesis, senescence, T-cell development or neurogenesis. Interacts with the TP53 protein to control genes that are important in proliferation and in the DNA-damage response. Mechanistically, the interaction inhibits the DNA binding and transcriptional activity of TP53/p53. Part of the transcriptional network modulating regulatory T-cell development and controls the generation of the regulatory T-cell pool under homeostatic conditions ; (Microbial infection) Plays a positive role in viral cDNA synthesis.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid cancer	DIS3VLDH	Definitive	Biomarker	[1]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Biomarker	[1]
Thyroid tumor	DISLVKMD	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[3]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[3]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[6]
Desmoplastic small round cell tumor	DISLI2ME	Strong	Biomarker	[7]
Differentiated thyroid carcinoma	DIS1V20Y	Strong	Biomarker	[8]
Follicular lymphoma	DISVEUR6	Strong	Altered Expression	[4]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[9]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[10]
Neoplasm of testis	DISK4XHT	Strong	Biomarker	[11]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[12]
Sarcoma	DISZDG3U	Strong	Biomarker	[10]
Seminoma	DIS3J8LJ	Strong	Biomarker	[13]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Altered Expression	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[15]
Lymphoma	DISN6V4S	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[19]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[20]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[21]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[22]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[23]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[29]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[30]

3 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 POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[25]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of POZ-, AT hook-, and zinc finger-containing protein 1 (PATZ1).	[27]

References

• [1] Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene.Cancers (Basel). 2018 Mar 27;10(4):92. doi: 10.3390/cancers10040092.
• [2] PATZ1 is a new prognostic marker of glioblastoma associated with the stem-like phenotype and enriched in the proneural subtype.Oncotarget. 2017 Jul 25;8(35):59282-59300. doi: 10.18632/oncotarget.19546. eCollection 2017 Aug 29.
• [3] Computational identification of potential transcriptional regulators of TGF-1 in human atherosclerotic arteries.Genomics. 2014 May-Jun;103(5-6):357-70. doi: 10.1016/j.ygeno.2014.05.001. Epub 2014 May 10.
• [4] PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas.Oncotarget. 2016 Sep 13;7(37):59158-59172. doi: 10.18632/oncotarget.10993.
• [5] PATZ1 Is Overexpressed in Pediatric Glial Tumors and Correlates with Worse Event-Free Survival in High-grade Gliomas.Cancers (Basel). 2019 Oct 11;11(10):1537. doi: 10.3390/cancers11101537.
• [6] Zinc finger protein 278, a potential oncogene in human colorectal cancer.Acta Biochim Biophys Sin (Shanghai). 2008 Apr;40(4):289-96. doi: 10.1111/j.1745-7270.2008.00405.x.
• [7] Spindle and Round Cell Sarcoma With EWSR1-PATZ1 Gene Fusion: A Sarcoma With Polyphenotypic Differentiation.Am J Surg Pathol. 2019 Feb;43(2):220-228. doi: 10.1097/PAS.0000000000001183.
• [8] PATZ1 knockdown enhances malignant phenotype in thyroid epithelial follicular cells and thyroid cancer cells.Oncotarget. 2017 Aug 2;8(47):82754-82772. doi: 10.18632/oncotarget.19787. eCollection 2017 Oct 10.
• [9] Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.BMC Bioinformatics. 2015 Apr 3;16:112. doi: 10.1186/s12859-015-0543-y.
• [10] Ewing sarcoma and Ewing-like tumors.Virchows Arch. 2020 Jan;476(1):109-119. doi: 10.1007/s00428-019-02720-8. Epub 2019 Dec 4.
• [11] PATZ1 gene has a critical role in the spermatogenesis and testicular tumours.J Pathol. 2008 May;215(1):39-47. doi: 10.1002/path.2323.
• [12] Identification of transcription regulatory relationships in rheumatoid arthritis and osteoarthritis.Clin Rheumatol. 2013 May;32(5):609-15. doi: 10.1007/s10067-012-2143-9. Epub 2013 Jan 8.
• [13] Down-regulation of oestrogen receptor- associates with transcriptional co-regulator PATZ1 delocalization in human testicular seminomas.J Pathol. 2011 May;224(1):110-20. doi: 10.1002/path.2846. Epub 2011 Mar 7.
• [14] PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration.Oncotarget. 2015 Mar 10;6(7):5310-23. doi: 10.18632/oncotarget.2776.
• [15] Clinical, pathological, and genomic features ofEWSR1-PATZ1 fusion sarcoma.Mod Pathol. 2019 Nov;32(11):1593-1604. doi: 10.1038/s41379-019-0301-1. Epub 2019 Jun 12.
• [16] POZ-, AT-hook-, and zinc finger-containing protein (PATZ) interacts with human oncogene B cell lymphoma 6 (BCL6) and is required for its negative autoregulation.J Biol Chem. 2012 May 25;287(22):18308-17. doi: 10.1074/jbc.M112.346270. Epub 2012 Apr 9.
• [17] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [18] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [21] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [22] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [23] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [24] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [25] 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.
• [26] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [27] 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.
• [28] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [29] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [30] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.