Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB5B2TY)

• DOT Name: Protein OS-9 (OS9)
• Synonyms: Amplified in osteosarcoma 9
• Gene Name: OS9
• Related Disease:
  Malignant soft tissue neoplasm
  Melanoma
  Rheumatoid arthritis
  Sarcoma
• UniProt ID: OS9_HUMAN
• PDB ID: 3AIH
• Pfam ID: PF07915
• Sequence:
  MAAETLLSSLLGLLLLGLLLPASLTGGVGSLNLEELSEMRYGIEILPLPVMGGQSQSSDV
  VIVSSKYKQRYECRLPAGAIHFQREREEETPAYQGPGIPELLSPMRDAPCLLKTKDWWTY
  EFCYGRHIQQYHMEDSEIKGEVLYLGYYQSAFDWDDETAKASKQHRLKRYHSQTYGNGSK
  CDLNGRPREAEVRFLCDEGAGISGDYIDRVDEPLSCSYVLTIRTPRLCPHPLLRPPPSAA
  PQAILCHPSLQPEEYMAYVQRQADSKQYGDKIIEELQDLGPQVWSETKSGVAPQKMAGAS
  PTKDDSKDSDFWKMLNEPEDQAPGGEEVPAEEQDPSPEAADSASGAPNDFQNNVQVKVIR
  SPADLIRFIEELKGGTKKGKPNIGQEQPVDDAAEVPQREPEKERGDPERQREMEEEEDED
  EDEDEDEDERQLLGEFEKELEGILLPSDRDRLRSEVKAGMERELENIIQETEKELDPDGL
  KKESERDRAMLALTSTLNKLIKRLEEKQSPELVKKHKKKRVVPKKPPPSPQPTEEDPEHR
  VRVRVTKLRLGGPNQDLTVLEMKRENPQLKQIEGLVKELLEREGLTAAGKIEIKIVRPWA
  EGTEEGARWLTDEDTRNLKEIFFNILVPGAEEAQKERQRQKELESNYRRVWGSPGGEGTG
  DLDEFDF
• Function: Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4.
• Tissue Specificity: Ubiquitously expressed. Found as well in all tumor cell lines analyzed, amplified in sarcomas. Highly expressed in osteosarcoma SJSA-1 and rhabdomyosarcoma Rh30 cell lines. Isoform 2 is the major isoform detected in all cell types examined.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Hedgehog ligand biogenesis (R-HSA-5358346)
  Hh mutants are degraded by ERAD (R-HSA-5362768)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  ER Quality Control Compartment (ERQC) (R-HSA-901032)
  ABC-family proteins mediated transport (R-HSA-382556)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant soft tissue neoplasm	DISTC6NO	Strong	Genetic Variation	[1]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]
Sarcoma	DISZDG3U	Strong	Genetic Variation	[1]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein OS-9 (OS9).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein OS-9 (OS9).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein OS-9 (OS9).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein OS-9 (OS9).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein OS-9 (OS9).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein OS-9 (OS9).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Protein OS-9 (OS9).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein OS-9 (OS9).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein OS-9 (OS9).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein OS-9 (OS9).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein OS-9 (OS9).	[12]

References

• [1] Genomic organization of the OS-9 gene amplified in human sarcomas.J Biochem. 1997 Dec;122(6):1190-5. doi: 10.1093/oxfordjournals.jbchem.a021880.
• [2] Identification of a new peptide recognized by autologous cytolytic T lymphocytes on a human melanoma.Cancer Immun. 2002 Jul 19;2:9.
• [3] Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [12] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] 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.