Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTO00PC)

• DOT Name: Ufm1-specific protease 2
• Synonyms: UfSP2; EC 3.4.22.-
• Gene Name: UFSP2
• Related Disease:
  Autosomal recessive non-syndromic intellectual disability
  Hip dysplasia, Beukes type
  Developmental and epileptic encephalopathy 106
• UniProt ID: UFSP2_HUMAN
• EC Number: 3.4.22.-
• Pfam ID: PF07910 ; PF20908
• Sequence:
  MVISESMDILFRIRGGLDLAFQLATPNEIFLKKALKHVLSDLSTKLSSNALVFRICHSSV
  YIWPSSDINTIPGELTDASACKNILRFIQFEPEEDIKRKFMRKKDKKLSDMHQIVNIDLM
  LEMSTSLAAVTPIIERESGGHHYVNMTLPVDAVISVAPEETWGKVRKLLVDAIHNQLTDM
  EKCILKYMKGTSIVVPEPLHFLLPGKKNLVTISYPSGIPDGQLQAYRKELHDLFNLPHDR
  PYFKRSNAYHFPDEPYKDGYIRNPHTYLNPPNMETGMIYVVQGIYGYHHYMQDRIDDNGW
  GCAYRSLQTICSWFKHQGYTERSIPTHREIQQALVDAGDKPATFVGSRQWIGSIEVQLVL
  NQLIGITSKILFVSQGSEIASQGRELANHFQSEGTPVMIGGGVLAHTILGVAWNEITGQI
  KFLILDPHYTGAEDLQVILEKGWCGWKGPDFWNKDAYYNLCLPQRPNMI
• Function: Thiol-dependent isopeptidase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins. Through TRIP4 deufmylation may regulate intracellular nuclear receptors transactivation and thereby regulate cell proliferation and differentiation.
• Tissue Specificity: Expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[1]
Hip dysplasia, Beukes type	DISSTSIF	Supportive	Autosomal dominant	[2]
Developmental and epileptic encephalopathy 106	DISK27VF	Limited	Unknown	[3]

9 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 Ufm1-specific protease 2.	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ufm1-specific protease 2.	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ufm1-specific protease 2.	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ufm1-specific protease 2.	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ufm1-specific protease 2.	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ufm1-specific protease 2.	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ufm1-specific protease 2.	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ufm1-specific protease 2.	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ufm1-specific protease 2.	[13]

1 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 Ufm1-specific protease 2.	[11]

References

• [1] A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy. Genet Med. 2021 May;23(5):900-908. doi: 10.1038/s41436-020-01071-z. Epub 2021 Jan 20.
• [2] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [3] Novel genetic causes for cerebral visual impairment. Eur J Hum Genet. 2016 May;24(5):660-5. doi: 10.1038/ejhg.2015.186. Epub 2015 Sep 9.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.