Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4L6TLL)

DOT Name Gem-associated protein 2 (GEMIN2)
Synonyms Gemin-2; Component of gems 2; Survival of motor neuron protein-interacting protein 1; SMN-interacting protein 1
Gene Name GEMIN2
Related Disease
Hirschsprung disease ( )
Mowat-Wilson syndrome ( )
Advanced cancer ( )
Age-related macular degeneration ( )
Aplasia cutis congenita ( )
Behcet disease ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Corpus callosum, agenesis of ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Epilepsy ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Intrahepatic cholangiocarcinoma ( )
Malignant mesothelioma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Oral cancer ( )
Oral cavity carcinoma ( )
Pancreatic cancer ( )
Restless legs syndrome ( )
Spinal muscular atrophy ( )
Squamous cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Uveitis ( )
Vasculitis ( )
Amyotrophic lateral sclerosis ( )
Carcinoma ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Marden-Walker syndrome ( )
Motor neurone disease ( )
Muckle-Wells syndrome ( )
Ovarian cancer ( )
Stomach cancer ( )
Adrenal adenoma ( )
Adrenocortical carcinoma ( )
Isolated congenital microcephaly ( )
UniProt ID
GEMI2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2LEH; 5XJL; 5XJQ; 5XJR; 5XJS; 5XJT; 5XJU
Pfam ID
PF04938
Sequence
MRRAELAGLKTMAWVPAESAVEELMPRLLPVEPCDLTEGFDPSVPPRTPQEYLRRVQIEA
AQCPDVVVAQIDPKKLKRKQSVNISLSGCQPAPEGYSPTLQWQQQQVAQFSTVRQNVNKH
RSHWKSQQLDSNVTMPKSEDEEGWKKFCLGEKLCADGAVGPATNESPGIDYVQIGFPPLL
SIVSRMNQATVTSVLEYLSNWFGERDFTPELGRWLYALLACLEKPLLPEAHSLIRQLARR
CSEVRLLVDSKDDERVPALNLLICLVSRYFDQRDLADEPS
Function
The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG (5Sm) are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Within the SMN complex, GEMIN2 constrains the conformation of 5Sm, thereby promoting 5Sm binding to snRNA containing the snRNP code (a nonameric Sm site and a 3'-adjacent stem-loop), thus preventing progression of assembly until a cognate substrate is bound.
Reactome Pathway
SARS-CoV-2 modulates host translation machinery (R-HSA-9754678 )
snRNP Assembly (R-HSA-191859 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hirschsprung disease DISUUSM1 Definitive Biomarker [1]
Mowat-Wilson syndrome DISD1AW7 Definitive Genetic Variation [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Age-related macular degeneration DIS0XS2C Strong Altered Expression [4]
Aplasia cutis congenita DISMDAYM Strong Altered Expression [5]
Behcet disease DISSYMBS Strong Altered Expression [6]
Bladder cancer DISUHNM0 Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Biomarker [8]
Cervical cancer DISFSHPF Strong Biomarker [9]
Cervical carcinoma DIST4S00 Strong Biomarker [9]
Colon cancer DISVC52G Strong Biomarker [10]
Colon carcinoma DISJYKUO Strong Biomarker [10]
Corpus callosum, agenesis of DISO9P40 Strong Altered Expression [5]
Endometrial cancer DISW0LMR Strong Altered Expression [11]
Endometrial carcinoma DISXR5CY Strong Altered Expression [11]
Epilepsy DISBB28L Strong Genetic Variation [12]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [14]
Intrahepatic cholangiocarcinoma DIS6GOC8 Strong Altered Expression [15]
Malignant mesothelioma DISTHJGH Strong Biomarker [16]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [17]
Neoplasm DISZKGEW Strong Altered Expression [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [19]
Oral cancer DISLD42D Strong Altered Expression [20]
Oral cavity carcinoma DISZXMVL Strong Altered Expression [20]
Pancreatic cancer DISJC981 Strong Altered Expression [21]
Restless legs syndrome DISNWY00 Strong Genetic Variation [22]
Spinal muscular atrophy DISTLKOB Strong Biomarker [23]
Squamous cell carcinoma DISQVIFL Strong Biomarker [24]
Urinary bladder cancer DISDV4T7 Strong Biomarker [7]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [7]
Uveitis DISV0RYS Strong Biomarker [6]
Vasculitis DISQRKDX Strong Biomarker [6]
Amyotrophic lateral sclerosis DISF7HVM moderate Biomarker [25]
Carcinoma DISH9F1N moderate Altered Expression [26]
Epithelial ovarian cancer DIS56MH2 moderate Biomarker [27]
Gastric cancer DISXGOUK moderate Biomarker [3]
Marden-Walker syndrome DISUAMD9 moderate Genetic Variation [28]
Motor neurone disease DISUHWUI moderate Biomarker [29]
Muckle-Wells syndrome DISMT3TQ moderate Genetic Variation [28]
Ovarian cancer DISZJHAP moderate Biomarker [27]
Stomach cancer DISKIJSX moderate Biomarker [3]
Adrenal adenoma DISC2UN8 Limited Altered Expression [5]
Adrenocortical carcinoma DISZF4HX Limited Biomarker [30]
Isolated congenital microcephaly DISUXHZ6 Limited Genetic Variation [31]
------------------------------------------------------------------------------------
⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Gem-associated protein 2 (GEMIN2). [32]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Gem-associated protein 2 (GEMIN2). [33]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Gem-associated protein 2 (GEMIN2). [34]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Gem-associated protein 2 (GEMIN2). [35]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Gem-associated protein 2 (GEMIN2). [36]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Gem-associated protein 2 (GEMIN2). [35]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Gem-associated protein 2 (GEMIN2). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Gem-associated protein 2 (GEMIN2). [39]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Gem-associated protein 2 (GEMIN2). [40]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Gem-associated protein 2 (GEMIN2). [41]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Drug(s)
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 affects the methylation of Gem-associated protein 2 (GEMIN2). [38]
------------------------------------------------------------------------------------

References

1 Mutations in Smad-interacting protein 1 gene are responsible for absence of its expression in Hirschsprung's disease.Clin Exp Med. 2018 Aug;18(3):445-451. doi: 10.1007/s10238-018-0496-3. Epub 2018 Mar 29.
2 Role of Zeb2/Sip1 in neuronal development.Brain Res. 2019 Feb 15;1705:24-31. doi: 10.1016/j.brainres.2018.09.034. Epub 2018 Sep 25.
3 Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer.Cell Physiol Biochem. 2017;42(3):1025-1036. doi: 10.1159/000478685. Epub 2017 Jun 28.
4 Transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization.Mol Vis. 2011;17:1222-30. Epub 2011 May 6.
5 Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?.Endocrine. 2017 Nov;58(2):276-288. doi: 10.1007/s12020-017-1409-z. Epub 2017 Sep 8.
6 Identification and characterization of the carboxy-terminal region of Sip-1, a novel autoantigen in Behet's disease.Arthritis Res Ther. 2006;8(3):R71. doi: 10.1186/ar1940. Epub 2006 Apr 12.
7 SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer.Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14884-9. doi: 10.1073/pnas.0902042106. Epub 2009 Aug 17.
8 Regulation of vimentin by SIP1 in human epithelial breast tumor cells.Oncogene. 2006 Aug 17;25(36):4975-85. doi: 10.1038/sj.onc.1209511. Epub 2006 Mar 27.
9 Long non-coding RNA NORAD upregulate SIP1 expression to promote cell proliferation and invasion in cervical cancer.Biomed Pharmacother. 2018 Oct;106:1454-1460. doi: 10.1016/j.biopha.2018.07.101. Epub 2018 Jul 24.
10 Neoexpression of N-cadherin in E-cadherin positive colon cancers.Int J Cancer. 2004 Sep 20;111(5):711-9. doi: 10.1002/ijc.20317.
11 The role of hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2 in endometrial cancer.Int J Cancer. 2011 Jun 1;128(11):2613-24. doi: 10.1002/ijc.25606. Epub 2010 Oct 4.
12 Sip-1 mutations cause disturbances in the activity of NMDA- and AMPA-, but not kainate receptors of neurons in the cerebral cortex.Neurosci Lett. 2017 May 22;650:180-186. doi: 10.1016/j.neulet.2017.04.048. Epub 2017 Apr 25.
13 Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma.J Exp Clin Cancer Res. 2014 May 10;33(1):40. doi: 10.1186/1756-9966-33-40.
14 SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation.BMC Cancer. 2011 Jun 6;11:223. doi: 10.1186/1471-2407-11-223.
15 MiR-590-3p suppresses epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma by inhibiting SIP1 expression.Oncotarget. 2017 May 23;8(21):34698-34708. doi: 10.18632/oncotarget.16150.
16 Expression of Snail, Slug and Sip1 in malignant mesothelioma effusions is associated with matrix metalloproteinase, but not with cadherin expression.Lung Cancer. 2006 Dec;54(3):309-17. doi: 10.1016/j.lungcan.2006.08.010. Epub 2006 Sep 25.
17 The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.Nat Cell Biol. 2008 May;10(5):593-601. doi: 10.1038/ncb1722. Epub 2008 Mar 30.
18 Expression of TWIST1, Snail, Slug, and NF-B and methylation of the TWIST1 promoter in mammary phyllodes tumor.Tumour Biol. 2013 Feb;34(1):445-53. doi: 10.1007/s13277-012-0569-y. Epub 2012 Nov 14.
19 Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells.Cancer Lett. 2010 Oct 28;296(2):216-24. doi: 10.1016/j.canlet.2010.04.008. Epub 2010 May 7.
20 Epigenetic inactivation of E-cadherin by promoter hypermethylation in oral carcinoma cells.Odontology. 2007 Jul;95(1):24-9. doi: 10.1007/s10266-007-0068-6. Epub 2007 Jul 25.
21 Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels.Cancer Res. 2010 Jul 1;70(13):5226-37. doi: 10.1158/0008-5472.CAN-09-4227. Epub 2010 Jun 15.
22 Possible joint origin of restless leg syndrome (RLS) and migraine.Med Hypotheses. 2007;69(1):64-6. doi: 10.1016/j.mehy.2006.10.060. Epub 2007 Jan 26.
23 Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes.J Clin Invest. 2018 Jul 2;128(7):3008-3023. doi: 10.1172/JCI95231. Epub 2018 Jun 11.
24 Transcription factors Snail, Slug, Twist, and SIP1 in spindle cell carcinoma of the head and neck.Virchows Arch. 2009 May;454(5):549-55. doi: 10.1007/s00428-009-0771-5. Epub 2009 Apr 21.
25 Increased expression level of the splicing variant of SIP1 in motor neuron diseases.Int J Biochem Cell Biol. 2002 Jun;34(6):699-707. doi: 10.1016/s1357-2725(01)00150-9.
26 Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin.J Pathol. 2007 Apr;211(5):507-515. doi: 10.1002/path.2138.
27 Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma: the important role of Snail in ovarian tumorigenesis and progression.Med Mol Morphol. 2009 Jun;42(2):82-91. doi: 10.1007/s00795-008-0436-5. Epub 2009 Jun 18.
28 Clinical features and management issues in Mowat-Wilson syndrome.Am J Med Genet A. 2006 Dec 15;140(24):2730-41. doi: 10.1002/ajmg.a.31530.
29 Gemins modulate the expression and activity of the SMN complex.Hum Mol Genet. 2005 Jun 15;14(12):1605-11. doi: 10.1093/hmg/ddi168. Epub 2005 Apr 20.
30 A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma.Endocr Pathol. 2017 Dec;28(4):326-331. doi: 10.1007/s12022-017-9482-7.
31 Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B.Am J Med Genet A. 2003 Jun 15;119A(3):257-65. doi: 10.1002/ajmg.a.20053.
32 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.
33 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
34 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.
35 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
36 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.
37 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
38 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.
39 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.
40 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
41 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.