Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG6F93V)

• DOT Name: Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2)
• Synonyms: PEST phosphatase-interacting protein 2
• Gene Name: PSTPIP2
• Related Disease:
  Arthritis
  Arteriosclerosis
  Atherosclerosis
  Cherubism
  Inflammation
  Majeed syndrome
  Osteomyelitis
  Chronic recurrent multifocal osteomyelitis
• UniProt ID: PPIP2_HUMAN
• Pfam ID: PF00611
• Sequence:
  MTRSLFKGNFWSADILSTIGYDNIIQHLNNGRKNCKEFEDFLKERAAIEERYGKDLLNLS
  RKKPCGQSEINTLKRALEVFKQQVDNVAQCHIQLAQSLREEARKMEEFREKQKLQRKKTE
  LIMDAIHKQKSLQFKKTMDAKKNYEQKCRDKDEAEQAVSRSANLVNPKQQEKLFVKLATS
  KTAVEDSDKAYMLHIGTLDKVREEWQSEHIKACEAFEAQECERINFFRNALWLHVNQLSQ
  QCVTSDEMYEQVRKSLEMCSIQRDIEYFVNQRKTGQIPPAPIMYENFYSSQKNAVPAGKA
  TGPNLARRGPLPIPKSSPDDPNYSLVDDYSLLYQ
• Function: Binds to F-actin. May be involved in regulation of the actin cytoskeleton.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Cherubism	DISHLJI0	Strong	Biomarker	[3]
Inflammation	DISJUQ5T	Strong	Biomarker	[4]
Majeed syndrome	DIS8AI2U	Strong	Biomarker	[5]
Osteomyelitis	DIS0VUZL	Strong	Biomarker	[6]
Chronic recurrent multifocal osteomyelitis	DIST1OU2	Disputed	Genetic Variation	[7]

1 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 Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2).	[19]

References

• [1] PSTPIP2 attenuates joint damage and suppresses inflammation in adjuvant-induced arthritis.Eur J Pharmacol. 2019 Sep 15;859:172558. doi: 10.1016/j.ejphar.2019.172558. Epub 2019 Jul 17.
• [2] Analysis of gene expression profile identifies potential biomarkers for atherosclerosis.Mol Med Rep. 2016 Oct;14(4):3052-8. doi: 10.3892/mmr.2016.5650. Epub 2016 Aug 19.
• [3] Autoinflammatory bone disorders.Curr Opin Rheumatol. 2007 Sep;19(5):492-8. doi: 10.1097/BOR.0b013e32825f5492.
• [4] PSTPIP2 Inhibits the Inflammatory Response and Proliferation of Fibroblast-Like Synoviocytes in vitro.Front Pharmacol. 2018 Dec 4;9:1432. doi: 10.3389/fphar.2018.01432. eCollection 2018.
• [5] Genetic susceptibility factors in a cohort of 38 patients with SAPHO syndrome: a study of PSTPIP2, NOD2, and LPIN2 genes.J Rheumatol. 2010 Feb;37(2):401-9. doi: 10.3899/jrheum.090456. Epub 2009 Dec 23.
• [6] Update on the genetics of nonbacterial osteomyelitis in humans.Curr Opin Rheumatol. 2018 Sep;30(5):521-525. doi: 10.1097/BOR.0000000000000530.
• [7] The nonreceptor tyrosine kinase SYK drives caspase-8/NLRP3 inflammasome-mediated autoinflammatory osteomyelitis.J Biol Chem. 2020 Mar 13;295(11):3394-3400. doi: 10.1074/jbc.RA119.010623. Epub 2019 Nov 12.
• [8] 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.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [14] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [17] 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.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] 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.