Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTMC0LH)

• DOT Name: Transcription factor SPT20 homolog (SUPT20H)
• Synonyms: p38-interacting protein; p38IP
• Gene Name: SUPT20H
• Related Disease:
  Lung adenocarcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Kidney cancer
  Plasma cell myeloma
  Prostate neoplasm
  Neoplasm
  Rheumatoid arthritis
• UniProt ID: SP20H_HUMAN
• PDB ID: 7KTR; 7KTS; 8H7G
• Pfam ID: PF12090
• Sequence:
  MQQALELALDRAEYVIESARQRPPKRKYLSSGRKSVFQKLYDLYIEECEKEPEVKKLRRN
  VNLLEKLVMQETLSCLVVNLYPGNEGYSLMLRGKNGSDSETIRLPYEEGELLEYLDAEEL
  PPILVDLLEKSQVNIFHCGCVIAEIRDYRQSSNMKSPGYQSRHILLRPTMQTLICDVHSI
  TSDNHKWTQEDKLLLESQLILATAEPLCLDPSIAVTCTANRLLYNKQKMNTRPMKRCFKR
  YSRSSLNRQQDLSHCPPPPQLRLLDFLQKRKERKAGQHYDLKISKAGNCVDMWKRSPCNL
  AIPSEVDVEKYAKVEKSIKSDDSQPTVWPAHDVKDDYVFECEAGTQYQKTKLTILQSLGD
  PLYYGKIQPCKADEESDSQMSPSHSSTDDHSNWFIIGSKTDAERVVNQYQELVQNEAKCP
  VKMSHSSSGSASLSQVSPGKETDQTETVSVQSSVLGKGVKHRPPPIKLPSSSGNSSSGNY
  FTPQQTSSFLKSPTPPPSSKPSSIPRKSSVDLNQVSMLSPAALSPASSSQRTTATQVMAN
  SAGLNFINVVGSVCGAQALMSGSNPMLGCNTGAITPAGINLSGLLPSGGLLPNALPSAMQ
  AASQAGVPFGLKNTSSLRPLNLLQLPGGSLIFNTLQQQQQQLSQFTPQQPQQPTTCSPQQ
  PGEQGSEQGSTSQEQALSAQQAAVINLTGVGSFMQSQAAVLSQLGSAENRPEQSLPQQRF
  QLSSAFQQQQQQIQQLRFLQHQMAMAAAAAQTAQLHHHRHTGSQSKSKMKRGTPTTPKF
• Function: Required for MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) activation during gastrulation. Required for down-regulation of E-cadherin during gastrulation by regulating E-cadherin protein level downstream from NCK-interacting kinase (NIK) and independently of the regulation of transcription by FGF signaling and Snail. Required for starvation-induced ATG9A trafficking during autophagy.
• Tissue Specificity: Highly expressed in testis, moderately in brain and pituitary gland. Expressed in several fetal tissues, including lung, brain, thymus and kidney. Expression is down-regulated in malignant prostate tissues.
• KEGG Pathway: Autophagy - animal (hsa04140)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Kidney cancer	DISBIPKM	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[6]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor SPT20 homolog (SUPT20H).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor SPT20 homolog (SUPT20H).	[13]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of Transcription factor SPT20 homolog (SUPT20H).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor SPT20 homolog (SUPT20H).	[17]

4 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 increases the methylation of Transcription factor SPT20 homolog (SUPT20H).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor SPT20 homolog (SUPT20H).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription factor SPT20 homolog (SUPT20H).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor SPT20 homolog (SUPT20H).	[16]

References

• [1] A new tumor-rejection antigen recognized by cytotoxic T lymphocytes infiltrating into a lung adenocarcinoma.Cancer Res. 2000 Sep 1;60(17):4830-7.
• [2] Quantification of C13orf19/P38IP mRNA expression by quantitative real-time PCR in patients with urological malignancies.Cancer Lett. 2005 Jul 28;225(2):253-60. doi: 10.1016/j.canlet.2004.10.037. Epub 2004 Dec 9.
• [3] Expression of the SART-1 tumor rejection antigen in breast cancer.Int J Cancer. 1999 Jan 5;80(1):64-7. doi: 10.1002/(sici)1097-0215(19990105)80:1<64::aid-ijc13>3.0.co;2-7.
• [4] p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma.Oral Oncol. 2016 Sep;60:81-9. doi: 10.1016/j.oraloncology.2016.06.010. Epub 2016 Jul 15.
• [5] MAGE-1 and related MAGE gene expression may be associated with hepatocellular carcinoma.J Cancer Res Clin Oncol. 1999 Dec;125(12):685-9. doi: 10.1007/s004320050334.
• [6] A molecular compendium of genes expressed in multiple myeloma.Blood. 2002 Sep 15;100(6):2175-86. doi: 10.1182/blood-2002-01-0008.
• [7] Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.Prostate. 2001 May 1;47(2):91-101. doi: 10.1002/pros.1051.
• [8] Cytotoxic-T-lymphocyte human papillomavirus type 16 E5 peptide with CpG-oligodeoxynucleotide can eliminate tumor growth in C57BL/6 mice.J Virol. 2004 Feb;78(3):1333-43. doi: 10.1128/jvi.78.3.1333-1343.2004.
• [9] A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families.PLoS One. 2019 Mar 7;14(3):e0213387. doi: 10.1371/journal.pone.0213387. eCollection 2019.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] 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.
• [15] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [16] 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.
• [17] 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.