General Information of Drug Off-Target (DOT) (ID: OTI4CYTF)

DOT Name AMSH-like protease (STAMBPL1)
Synonyms AMSH-LP; EC 3.4.19.-; STAM-binding protein-like 1
Gene Name STAMBPL1
Related Disease
Gastric cancer ( )
Stomach cancer ( )
Adult T-cell leukemia/lymphoma ( )
Familial thoracic aortic aneurysm and aortic dissection ( )
Multisystemic smooth muscle dysfunction syndrome ( )
Nasopharyngeal carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal carcinoma ( )
Renal cell carcinoma ( )
Aortic aneurysm, familial thoracic 6 ( )
Lung cancer ( )
Lung carcinoma ( )
UniProt ID
STALP_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2ZNR; 2ZNV; 7L97
EC Number
3.4.19.-
Pfam ID
PF01398 ; PF08969
Sequence
MDQPFTVNSLKKLAAMPDHTDVSLSPEERVRALSKLGCNITISEDITPRRYFRSGVEMER
MASVYLEEGNLENAFVLYNKFITLFVEKLPNHRDYQQCAVPEKQDIMKKLKEIAFPRTDE
LKNDLLKKYNVEYQEYLQSKNKYKAEILKKLEHQRLIEAERKRIAQMRQQQLESEQFLFF
EDQLKKQELARGQMRSQQTSGLSEQIDGSALSCFSTHQNNSLLNVFADQPNKSDATNYAS
HSPPVNRALTPAATLSAVQNLVVEGLRCVVLPEDLCHKFLQLAESNTVRGIETCGILCGK
LTHNEFTITHVIVPKQSAGPDYCDMENVEELFNVQDQHDLLTLGWIHTHPTQTAFLSSVD
LHTHCSYQLMLPEAIAIVCSPKHKDTGIFRLTNAGMLEVSACKKKGFHPHTKEPRLFSIC
KHVLVKDIKIIVLDLR
Function
Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Acts as a positive regulator of the TORC1 signaling pathway by mediating 'Lys-63'-linked deubiquitination of SESN2, thereby inhibiting SESN2-interaction with the GATOR2 complex. Does not cleave 'Lys-48'-linked polyubiquitin chains.
Tissue Specificity Ubiquitously expressed.
Reactome Pathway
Metalloprotease DUBs (R-HSA-5689901 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Gastric cancer DISXGOUK Definitive Biomarker [1]
Stomach cancer DISKIJSX Definitive Biomarker [1]
Adult T-cell leukemia/lymphoma DIS882XU Strong Biomarker [2]
Familial thoracic aortic aneurysm and aortic dissection DIS069FB Strong CausalMutation [3]
Multisystemic smooth muscle dysfunction syndrome DISV2K69 Strong CausalMutation [3]
Nasopharyngeal carcinoma DISAOTQ0 Strong Genetic Variation [4]
Prostate cancer DISF190Y Strong Biomarker [5]
Prostate carcinoma DISMJPLE Strong Biomarker [5]
Renal carcinoma DISER9XT Strong Altered Expression [6]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [6]
Aortic aneurysm, familial thoracic 6 DISNTSXF moderate CausalMutation [7]
Lung cancer DISCM4YA Limited Genetic Variation [8]
Lung carcinoma DISTR26C Limited Genetic Variation [8]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
19 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 AMSH-like protease (STAMBPL1). [9]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of AMSH-like protease (STAMBPL1). [10]
Tretinoin DM49DUI Approved Tretinoin increases the expression of AMSH-like protease (STAMBPL1). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of AMSH-like protease (STAMBPL1). [12]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of AMSH-like protease (STAMBPL1). [13]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of AMSH-like protease (STAMBPL1). [14]
Estradiol DMUNTE3 Approved Estradiol increases the expression of AMSH-like protease (STAMBPL1). [15]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of AMSH-like protease (STAMBPL1). [16]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of AMSH-like protease (STAMBPL1). [17]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of AMSH-like protease (STAMBPL1). [18]
Melphalan DMOLNHF Approved Melphalan decreases the expression of AMSH-like protease (STAMBPL1). [19]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of AMSH-like protease (STAMBPL1). [20]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of AMSH-like protease (STAMBPL1). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of AMSH-like protease (STAMBPL1). [23]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of AMSH-like protease (STAMBPL1). [24]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of AMSH-like protease (STAMBPL1). [25]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of AMSH-like protease (STAMBPL1). [18]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of AMSH-like protease (STAMBPL1). [27]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of AMSH-like protease (STAMBPL1). [28]
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⏷ Show the Full List of 19 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Camptothecin DM6CHNJ Phase 3 Camptothecin increases the methylation of AMSH-like protease (STAMBPL1). [22]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of AMSH-like protease (STAMBPL1). [26]
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References

1 STAMBPL1 knockdown has antitumour effects on gastric cancer biological activities.Oncol Lett. 2019 Nov;18(5):4421-4428. doi: 10.3892/ol.2019.10789. Epub 2019 Sep 3.
2 An RNA interference screen identifies the Deubiquitinase STAMBPL1 as a critical regulator of human T-cell leukemia virus type 1 tax nuclear export and NF-B activation.J Virol. 2012 Mar;86(6):3357-69. doi: 10.1128/JVI.06456-11. Epub 2012 Jan 18.
3 Neonatal stroke and progressive leukoencephalopathy in a child with an ACTA2 mutation.J Child Neurol. 2013 Apr;28(4):531-4. doi: 10.1177/0883073812446631. Epub 2012 Jun 29.
4 A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
5 Targeting the deubiquitinase STAMBPL1 triggers apoptosis in prostate cancer cells by promoting XIAP degradation.Cancer Lett. 2019 Aug 1;456:49-58. doi: 10.1016/j.canlet.2019.04.020. Epub 2019 Apr 17.
6 Cepharanthine Enhances TRAIL-Mediated Apoptosis Through STAMBPL1-Mediated Downregulation of Survivin Expression in Renal Carcinoma Cells.Int J Mol Sci. 2018 Oct 22;19(10):3280. doi: 10.3390/ijms19103280.
7 Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings.Brain Dev. 2017 Jan;39(1):62-66. doi: 10.1016/j.braindev.2016.08.003. Epub 2016 Aug 25.
8 Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study.Cancer Res. 2009 Aug 15;69(16):6633-41. doi: 10.1158/0008-5472.CAN-09-0680. Epub 2009 Aug 4.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 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.
11 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
12 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
13 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.
14 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
15 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.
16 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.
17 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
18 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
19 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
20 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
21 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
22 Reduced camptothecin sensitivity of estrogen receptor-positive human breast cancer cells following exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with DNA methylation changes. Environ Toxicol. 2019 Apr;34(4):401-414.
23 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
24 Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
25 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
26 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.
27 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
28 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.