Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8NCK82)

DOT Name Protein phosphatase Slingshot homolog 2 (SSH2)
Synonyms EC 3.1.3.16; EC 3.1.3.48; SSH-like protein 2; SSH-2L; hSSH-2L
Gene Name SSH2
Related Disease
Advanced cancer ( )
Birt-Hogg-Dube syndrome ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Hip dysplasia, Beukes type ( )
Neoplasm ( )
Renal cell carcinoma ( )
Thyroid gland carcinoma ( )
UniProt ID
SSH2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2NT2
EC Number
3.1.3.16; 3.1.3.48
Pfam ID
PF08766 ; PF00782
Sequence
MALVTVQRSPTPSTTSSPCASEADSGEEECRSQPRSISESFLTVKGAALFLPRGNGSSTP
RISHRRNKHAGDLQQHLQAMFILLRPEDNIRLAVRLESTYQNRTRYMVVVSTNGRQDTEE
SIVLGMDFSSNDSSTCTMGLVLPLWSDTLIHLDGDGGFSVSTDNRVHIFKPVSVQAMWSA
LQSLHKACEVARAHNYYPGSLFLTWVSYYESHINSDQSSVNEWNAMQDVQSHRPDSPALF
TDIPTERERTERLIKTKLREIMMQKDLENITSKEIRTELEMQMVCNLREFKEFIDNEMIV
ILGQMDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVY
DEEATDLLAYWNDTYKFISKAKKHGSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYD
YVKERRTVTKPNPSFMRQLEEYQGILLASKQRHNKLWRSHSDSDLSDHHEPICKPGLELN
KKDITTSADQIAEVKTMESHPPIPPVFVEHMVPQDANQKGLCTKERMICLEFTSREFHAG
QIEDELNLNDINGCSSGCCLNESKFPLDNCHASKALIQPGHVPEMANKFPDLTVEDLETD
ALKADMNVHLLPMEELTSPLKDPPMSPDPESPSPQPSCQTEISDFSTDRIDFFSALEKFV
ELSQETRSRSFSHSRMEELGGGRNESCRLSVVEVAPSKVTADDQRSSSLSNTPHASEESS
MDEEQSKAISELVSPDIFMQSHSENAISVKEIVTEIESISQGVGQIQLKGDILPNPCHTP
KKNSIHELLLERAQTPENKPGHMEQDEDSCTAQPELAKDSGMCNPEGCLTTHSSIADLEE
GEPAEGEQELQGSGMHPGAKWYPGSVRRATLEFEERLRQEQEHHGAAPTCTSLSTRKNSK
NDSSVADLAPKGKSDEAPPEHSFVLKEPEMSKGKGKYSGSEAGSLSHSEQNATVPAPRVL
EFDHLPDPQEGPGSDTGTQQEGVLKDLRTVIPYQESETQAVPLPLPKRVEIIEYTHIVTS
PNHTGPGSEIATSEKSGEQGLRKVNMEKSVTVLCTLDENLNRTLDPNQVSLHPQVLPLPH
SSSPEHNRPTDHPTSILSSPEDRGSSLSTALETAAPFVSHTTHLLSASLDYLHPQTMVHL
EGFTEQSSTTDEPSAEQVSWEESQESPLSSGSEVPYKDSQLSSADLSLISKLGDNTGELQ
EKMDPLPVACRLPHSSSSENIKSLSHSPGVVKERAKEIESRVVFQAGLTKPSQMRRSASL
AKLGYLDLCKDCLPEREPASCESPHLKLLQPFLRTDSGMHAMEDQESLENPGAPHNPEPT
KSFVEQLTTTECIVQSKPVERPLVQYAKEFGSSQQYLLPRAGLELTSSEGGLPVLQTQGL
QCACPAPGLAVAPRQQHGRTHPLRRLKKANDKKRTTNPFYNTM
Function
Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. Required for spermatogenesis. Involved in acrosome biogenesis, probably by regulating cofilin-mediated actin cytoskeleton remodeling during proacrosomal vesicle fusion and/or Golgi to perinuclear vesicle trafficking.
KEGG Pathway
Axon guidance (hsa04360 )
Regulation of actin cytoskeleton (hsa04810 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Birt-Hogg-Dube syndrome DISIN5TD Strong Biomarker [2]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [2]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [3]
Hip dysplasia, Beukes type DISSTSIF Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [2]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [2]
Thyroid gland carcinoma DISMNGZ0 Strong Altered Expression [2]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 phosphatase Slingshot homolog 2 (SSH2). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Protein phosphatase Slingshot homolog 2 (SSH2). [13]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Protein phosphatase Slingshot homolog 2 (SSH2). [15]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Protein phosphatase Slingshot homolog 2 (SSH2). [15]
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10 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 phosphatase Slingshot homolog 2 (SSH2). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [7]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [9]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [10]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Protein phosphatase Slingshot homolog 2 (SSH2). [16]
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⏷ Show the Full List of 10 Drug(s)

References

1 Exome sequencing in 51 early onset non-familial CRC cases.Mol Genet Genomic Med. 2019 May;7(5):e605. doi: 10.1002/mgg3.605. Epub 2019 Feb 27.
2 Knockdown of Slingshot 2 (SSH2) serine phosphatase induces Caspase3 activation in human carcinoma cell lines with the loss of the Birt-Hogg-Dub tumour suppressor gene (FLCN).Oncogene. 2014 Feb 20;33(8):956-65. doi: 10.1038/onc.2013.27. Epub 2013 Feb 18.
3 miR-194 Inhibits the Proliferation of SW620 Colon Cancer Stem Cells Through Downregulation of SSH2 Expression.Cancer Manag Res. 2019 Dec 4;11:10229-10238. doi: 10.2147/CMAR.S221150. eCollection 2019.
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 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
7 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.
8 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
9 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.
10 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
11 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
14 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.
15 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.
16 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.