Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZZWR7L)

• DOT Name: Circadian clock protein PASD1 (PASD1)
• Synonyms: Cancer/testis antigen 63; CT63; OX-TES-1; PAS domain-containing protein 1
• Gene Name: PASD1
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Glioma
  Plasma cell myeloma
  Testicular cancer
  Adult lymphoma
  B-cell lymphoma
  Lymphoma
  Pediatric lymphoma
• UniProt ID: PASD1_HUMAN
• Sequence:
  MKMRGEKRRDKVNPKSSQRKLNWIPSFPTYDYFNQVTLQLLDGFMITLSTDGVIICVAEN
  ISSLLGHLPAEIVGKKLLSLLPDEEKDEVYQKIILKFPLLNSETHIEFCCHLKRGNVEHG
  DSSAYENVKFIVNVRDICNEFPVVFSGLFSSHLCADFAACVPQEDRLYLVGNVCILRTQL
  LQQLYTSKAVSDEAVLTQDSDEEPFVGELSSSQGQRGHTSMKAVYVEPAAAAAAAAISDD
  QIDIAEVEQYGPQENVHMFVDSDSTYCSSTVFLDTMPESPALSLQDFRGEPEVNPLYRAD
  PVDLEFSVDQVDSVDQEGPMDQQDPENPVAPLDQAGLMDPVDPEDSVDLGAAGASAQPLQ
  PSSPVAYDIISQELELMKKLKEQLEERTWLLHDAIQNQQNALELMMDHLQKQPNTLRHVV
  IPDLQSSEAVPKKQQKQHAGQVKRPLPHPKDVKCFCGLSLSNSLKNTGELQEPCVAFNQQ
  QLVQQEQHLKEQQRQLREQLQQLREQRKVQKQKKMQEKKKLQEQKMQEKKKLQEQRRQKK
  KKLQERKKWQGQMLQKEPEEEQQKQQLQEQPLKHNVIVGNERVQICLQNPRDVSVPLCNH
  PVRFLQAQPIVPVQRAAEQQPSGFYQDENCGQQEDESQSFYPEAYQGPPVNQLPLIDTSN
  SEAISSSSIPQFPITSDSTISTLETPQDYIRLWQELSDSLGPVVQVNTWSCDEQGTLHGQ
  PTYHQVQVSEVGVEGPPDPQAFQGPAAYQPDQMRSAEQTRLMPAEQRDSNKPC
• Function: Functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body. Acts as a nuclear repressor of the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock components. Inhibits circadian clock function in cancer cells, when overexpressed.
• Tissue Specificity: Testis-specific . Expressed in a broad range of cancer cells, including melanoma, lung cancer, and breast cancer (at protein level). Testis-specific . Found in histologically normal tissues from patients with uterus, lung and small intestine cancers. Widespread expression seen in solid tumors and diffuse large B-cell lymphoma (DLBCL)-derived cell lines. Isoform 2 is expressed in all DLBCL-derived cell lines, while isoform 1 is preferentially expressed in cell lines derived from non-germinal center DLBCL .

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[3]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[3]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Limited	Altered Expression	[4]
Lymphoma	DISN6V4S	Limited	Biomarker	[4]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[4]

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 Circadian clock protein PASD1 (PASD1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Circadian clock protein PASD1 (PASD1).	[6]

References

• [1] PAS Domain Containing Repressor 1 (PASD1) Promotes Glioma Cell Proliferation Through Inhibiting Apoptosis In Vitro.Med Sci Monit. 2019 Sep 16;25:6955-6964. doi: 10.12659/MSM.916308.
• [2] Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer.Immunotherapy. 2019 Oct;11(14):1205-1219. doi: 10.2217/imt-2019-0073. Epub 2019 Sep 3.
• [3] DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma.Leukemia. 2010 Nov;24(11):1951-9. doi: 10.1038/leu.2010.196. Epub 2010 Sep 23.
• [4] A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein.Br J Cancer. 2004 Jul 5;91(1):141-9. doi: 10.1038/sj.bjc.6601875.
• [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] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.