Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8S0OO8)

DOT Name Intersectin-2 (ITSN2)
Synonyms SH3 domain-containing protein 1B; SH3P18; SH3P18-like WASP-associated protein
Gene Name ITSN2
Related Disease
Alzheimer disease ( )
Bipolar disorder ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Depression ( )
Late-onset Parkinson disease ( )
Nephrotic syndrome ( )
Prostate cancer ( )
Prostate neoplasm ( )
Schizophrenia ( )
Sjogren syndrome ( )
Asthma ( )
UniProt ID
ITSN2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1J3T; 1UDL; 1UE9; 1UFF; 1UHF; 3GF9; 3JZY; 4IIO
Pfam ID
PF00168 ; PF12763 ; PF16652 ; PF00621 ; PF00018 ; PF07653 ; PF14604
Sequence
MMAQFPTAMNGGPNMWAITSEERTKHDRQFDNLKPSGGYITGDQARNFFLQSGLPAPVLA
EIWALSDLNKDGKMDQQEFSIAMKLIKLKLQGQQLPVVLPPIMKQPPMFSPLISARFGMG
SMPNLSIPQPLPPAAPITSLSSATSGTNLPPLMMPTPLVPSVSTSSLPNGTASLIQPLPI
PYSSSTLPHGSSYSLMMGGFGGASIQKAQSLIDLGSSSSTSSTASLSGNSPKTGTSEWAV
PQPTRLKYRQKFNTLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADVDGDGQLKAE
EFILAMHLTDMAKAGQPLPLTLPPELVPPSFRGGKQIDSINGTLPSYQKMQEEEPQKKLP
VTFEDKRKANYERGNMELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQL
ELEKRLEKQRELERQREEERRKDIERREAAKQELERQRRLEWERIRRQELLNQKNREQEE
IVRLNSKKKNLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQL
QQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTPDSGVSLLHKKSLEKEELCQRLKEQLD
ALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRETYNTQQLA
LEQLYKIKRDKLKEIERKRLELMQKKKLEDEAARKAKQGKENLWKENLRKEEEEKQKRLQ
EEKTQEKIQEEERKAEEKQRKDKDTLKAEEKKRETASVLVNYRALYPFEARNHDEMSFNS
GDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEKMPSSENEKAVSPKKALLPPTVSLSA
TSTSSEPLSSNQPASVTDYQNVSFSNLTVNTSWQKKSAFTRTVSPGSVSPIHGQGQVVEN
LKAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKIIPGSEVK
REEPEALYAAVNKKPTSAAYSVGEEYIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTG
SIGDRSGIFPSNYVKPKDQESFGSASKSGASNKKPEIAQVTSAYVASGSEQLSLAPGQLI
LILKKNTSGWWQGELQARGKKRQKGWFPASHVKLLGPSSERATPAFHPVCQVIAMYDYAA
NNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKMTTDSDPSQQWCADLQTL
DTMQPIERKRQGYIHELIQTEERYMADLQLVVEVFQKRMAESGFLTEGEMALIFVNWKEL
IMSNTKLLKALRVRKKTGGEKMPVQMIGDILAAELSHMQAYIRFCSCQLNGAALLQQKTD
EDTDFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTPESHADHSSLKL
ALERAEELCSQVNEGVREKENSDRLEWIQAHVQCEGLAEQLIFNSLTNCLGPRKLLHSGK
LYKTKSNKELHGFLFNDFLLLTYMVKQFAVSSGSEKLFSSKSNAQFKMYKTPIFLNEVLV
KLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKKKREKAYQA
RSQKTSGIGRLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNC
QFFIKDLYQDVLCLTLFDRDQFSPDDFLGRTEIPVAKIRTEQESKGPMTRRLLLHEVPTG
EVWVRFDLQLFEQKTLL
Function
Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes.
Tissue Specificity Expressed in melanocytes . Ubiquitous. Isoform 1 is primarily expressed in adult heart and liver.
Reactome Pathway
Clathrin-mediated endocytosis (R-HSA-8856828 )
RHOU GTPase cycle (R-HSA-9013420 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
Bipolar disorder DISAM7J2 Strong Altered Expression [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Breast neoplasm DISNGJLM Strong Biomarker [3]
Depression DIS3XJ69 Strong Biomarker [4]
Late-onset Parkinson disease DIS9IOUI Strong Genetic Variation [5]
Nephrotic syndrome DISSPSC2 Strong Biomarker [6]
Prostate cancer DISF190Y Strong Biomarker [7]
Prostate neoplasm DISHDKGQ Strong Biomarker [7]
Schizophrenia DISSRV2N Strong Biomarker [8]
Sjogren syndrome DISUBX7H Strong Biomarker [9]
Asthma DISW9QNS Limited Genetic Variation [10]
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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
6 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 Intersectin-2 (ITSN2). [11]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Intersectin-2 (ITSN2). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Intersectin-2 (ITSN2). [21]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Intersectin-2 (ITSN2). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Intersectin-2 (ITSN2). [23]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Intersectin-2 (ITSN2). [15]
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⏷ Show the Full List of 6 Drug(s)
11 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 Intersectin-2 (ITSN2). [12]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Intersectin-2 (ITSN2). [13]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Intersectin-2 (ITSN2). [14]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Intersectin-2 (ITSN2). [16]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Intersectin-2 (ITSN2). [17]
Marinol DM70IK5 Approved Marinol decreases the expression of Intersectin-2 (ITSN2). [18]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the expression of Intersectin-2 (ITSN2). [19]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Intersectin-2 (ITSN2). [20]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Intersectin-2 (ITSN2). [22]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Intersectin-2 (ITSN2). [24]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Intersectin-2 (ITSN2). [25]
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⏷ Show the Full List of 11 Drug(s)

References

1 Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
2 You'll feel better in the morning: slow wave activity and overnight mood regulation in interepisode bipolar disorder.Psychol Med. 2018 Jan;48(2):249-260. doi: 10.1017/S0033291717001581. Epub 2017 Jun 19.
3 Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy.Breast Cancer Res Treat. 2009 Nov;118(1):45-56. doi: 10.1007/s10549-008-0207-y. Epub 2008 Oct 17.
4 Personality Factors and Depressive Configurations. An Exploratory Study in an Italian Clinical Sample.Front Psychol. 2017 Mar 3;8:251. doi: 10.3389/fpsyg.2017.00251. eCollection 2017.
5 Personality and Personality Disorders in Medication-Overuse Headache: A Controlled Study by SWAP-200.Pain Res Manag. 2019 Jun 12;2019:1874078. doi: 10.1155/2019/1874078. eCollection 2019.
6 Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nat Commun. 2018 May 17;9(1):1960. doi: 10.1038/s41467-018-04193-w.
7 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
8 Schizotypy and personality profiles of Cluster A in a group of schizophrenic patients and their siblings.BMC Psychiatry. 2013 Oct 4;13:245. doi: 10.1186/1471-244X-13-245.
9 Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjgren's syndrome.Nat Genet. 2013 Nov;45(11):1284-92. doi: 10.1038/ng.2792. Epub 2013 Oct 6.
10 Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.Nat Genet. 2018 Jan;50(1):42-53. doi: 10.1038/s41588-017-0014-7. Epub 2017 Dec 22.
11 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.
12 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.
13 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.
14 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
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 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
17 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.
18 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
19 Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
20 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
21 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.
22 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.
23 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
24 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
25 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.