Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQZNQQ5)

• DOT Name: SRC kinase signaling inhibitor 1 (SRCIN1)
• Synonyms: SNAP-25-interacting protein; SNIP; p130Cas-associated protein; p140Cap
• Gene Name: SRCIN1
• Related Disease:
  Advanced cancer
  Autism
  Bone osteosarcoma
  Brain disease
  Breast neoplasm
  Cocaine addiction
  Cognitive impairment
  Epilepsy
  Intellectual disability
  Lung adenocarcinoma
  Lupus
  Neoplasm
  Nervous system disease
  Osteosarcoma
  Schizophrenia
  Systemic lupus erythematosus
  Colorectal carcinoma
  Neuroblastoma
  Pancreatic cancer
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Adenocarcinoma
  Amyotrophic lateral sclerosis
  Carcinoma of liver and intrahepatic biliary tract
  Cutaneous squamous cell carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Liver cancer
  Stomach cancer
• UniProt ID: SRCN1_HUMAN
• Pfam ID: PF03915
• Sequence:
  MGNAPSQDPERSSPPMLSADDAEYPREYRTLGGGGGGGSGGRRFSNVGLVHTSERRHTVI
  AAQSLEALSGLQKADADRKRDAFMDHLKSKYPQHALALRGQQDRMREQPNYWSFKTRSSR
  HTQGAQPGLADQAAKLSYASAESLETMSEAELPLGFSRMNRFRQSLPLSRSASQTKLRSP
  GVLFLQFGEETRRVHITHEVSSLDTLHALIAHMFPQKLTMGMLKSPNTAILIKDEARNVF
  YELEDVRDIQDRSIIKIYRKEPLYAAFPGSHLTNGDLRREMVYASRESSPTRRLNNLSPA
  PHLASGSPPPGLPSGLPSGLQSGSPSRSRLSYAGGRPPSYAGSPVHHAAERLGGAPAAQG
  VSPSPSAILERRDVKPDEDLASKAGGMVLVKGEGLYADPYGLLHEGRLSLAAAAGDPFAY
  PGAGGLYKRGSVRSLSTYSAAALQSDLEDSLYKAAGGGGPLYGDGYGFRLPPSSPQKLAD
  VAAPPGGPPPPHSPYSGPPSRGSPVRQSFRKDSGSSSVFAESPGGKTRSAGSASTAGAPP
  SELFPGPGERSLVGFGPPVPAKDTETRERMEAMEKQIASLTGLVQSALLRGSEPETPSEK
  IEGSNGAATPSAPCGSGGRSSGATPVSGPPPPSASSTPAGQPTAVSRLQMQLHLRGLQNS
  ASDLRGQLQQLRKLQLQNQESVRALLKRTEAELSMRVSEAARRQEDPLQRQRTLVEEERL
  RYLNDEELITQQLNDLEKSVEKIQRDVSHNHRLVPGPELEEKALVLKQLGETLTELKAHF
  PGLQSKMRVVLRVEVEAVKFLKEEPQRLDGLLKRCRGVTDTLAQIRRQVDEGVWPPPNNL
  LSQSPKKVTAETDFNKSVDFEMPPPSPPLNLHELSGPAEGASLTPKGGNPTKGLDTPGKR
  SVDKAVSVEAAERDWEEKRAALTQYSAKDINRLLEETQAELLKAIPDLDCASKAHPGPAP
  TPDHKPPKAPHGQKAAPRTEPSGRRGSDELTVPRYRTEKPSKSPPPPPPRRSFPSSHGLT
  TTRTGEVVVTSKKDSAFIKKAESEELEVQKPQVKLRRAVSEVARPASTPPIMASAIKDED
  DEDRIIAELESGGGSVPPMKVVTPGASRLKAAQGQAGSPDKSKHGKQRAEYMRIQAQQQA
  TKPSKEMSGSNETSSPVSEKPSASRTSIPVLTSFGARNSSISF
• Function: Acts as a negative regulator of SRC by activating CSK which inhibits SRC activity and downstream signaling, leading to impaired cell spreading and migration. Regulates dendritic spine morphology. Involved in calcium-dependent exocytosis. May play a role in neurotransmitter release or synapse maintenance.
• Tissue Specificity: Expressed in some primary breast carcinomas where its presence is significantly associated with increased tumor size. Not detected in normal breast tissue.

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Brain disease	DIS6ZC3X	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Cocaine addiction	DISHTRXG	Strong	Therapeutic	[5]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[2]
Epilepsy	DISBB28L	Strong	Altered Expression	[2]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[2]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[6]
Lupus	DISOKJWA	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[2]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[9]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[8]
Pancreatic cancer	DISJC981	moderate	Biomarker	[10]
Lung cancer	DISCM4YA	Disputed	Biomarker	[11]
Lung carcinoma	DISTR26C	Disputed	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[11]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[12]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[13]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[14]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[15]
Gastric cancer	DISXGOUK	Limited	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[17]
Liver cancer	DISDE4BI	Limited	Biomarker	[14]
Stomach cancer	DISKIJSX	Limited	Biomarker	[16]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SRC kinase signaling inhibitor 1 (SRCIN1).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of SRC kinase signaling inhibitor 1 (SRCIN1).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SRC kinase signaling inhibitor 1 (SRCIN1).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SRC kinase signaling inhibitor 1 (SRCIN1).	[25]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SRC kinase signaling inhibitor 1 (SRCIN1).	[19]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of SRC kinase signaling inhibitor 1 (SRCIN1).	[20]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of SRC kinase signaling inhibitor 1 (SRCIN1).	[21]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of SRC kinase signaling inhibitor 1 (SRCIN1).	[23]

References

• [1] Dissecting the Shared and Context-Dependent Pathways Mediated by the p140Cap Adaptor Protein in Cancer and in Neurons.Front Cell Dev Biol. 2019 Oct 15;7:222. doi: 10.3389/fcell.2019.00222. eCollection 2019.
• [2] Synaptic Interactome Mining Reveals p140Cap as a New Hub for PSD Proteins Involved in Psychiatric and Neurological Disorders.Front Mol Neurosci. 2017 Jun 30;10:212. doi: 10.3389/fnmol.2017.00212. eCollection 2017.
• [3] miR-17-5p promotes proliferation and epithelial-mesenchymal transition in human osteosarcoma cells by targeting SRC kinase signaling inhibitor 1.J Cell Biochem. 2019 Apr;120(4):5495-5504. doi: 10.1002/jcb.27832. Epub 2018 Oct 9.
• [4] SNIP/p140Cap mRNA expression is an unfavourable prognostic factor in breast cancer and is not expressed in normal breast tissue.Br J Cancer. 2008 May 20;98(10):1641-5. doi: 10.1038/sj.bjc.6604365. Epub 2008 May 13.
• [5] Histone arginine methylation in cocaine action in the nucleus accumbens. Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9623-8. doi: 10.1073/pnas.1605045113. Epub 2016 Aug 9.
• [6] miR-150 promotes the proliferation and migration of lung cancer cells by targeting SRC kinase signalling inhibitor 1.Eur J Cancer. 2014 Mar;50(5):1013-24. doi: 10.1016/j.ejca.2013.12.024. Epub 2014 Jan 20.
• [7] Lupus Regulator Peptide P140 Represses B Cell Differentiation by Reducing HLA Class II Molecule Overexpression.Arthritis Rheumatol. 2018 Jul;70(7):1077-1088. doi: 10.1002/art.40470. Epub 2018 May 15.
• [8] The SRCIN1/p140Cap adaptor protein negatively regulates the aggressiveness of neuroblastoma.Cell Death Differ. 2020 Feb;27(2):790-807. doi: 10.1038/s41418-019-0386-6. Epub 2019 Jul 8.
• [9] MicroRNA-181a promotes angiogenesis in colorectal cancer by targeting SRCIN1 to promote the SRC/VEGF signaling pathway.Cell Death Dis. 2018 Apr 1;9(4):438. doi: 10.1038/s41419-018-0490-4.
• [10] MicroRNA-374a promotes pancreatic cancer cell proliferation and epithelial to mesenchymal transition by targeting SRCIN1.Pathol Res Pract. 2019 Jun;215(6):152382. doi: 10.1016/j.prp.2019.03.011. Epub 2019 Mar 5.
• [11] MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1.Oncol Res. 2019 Aug 8;27(8):879-887. doi: 10.3727/096504018X15451308507747. Epub 2019 Apr 14.
• [12] p140Cap suppresses the invasive properties of highly metastatic MTLn3-EGFR cells via impaired cortactin phosphorylation.Oncogene. 2012 Feb 2;31(5):624-33. doi: 10.1038/onc.2011.257. Epub 2011 Jul 4.
• [13] Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis.J Neurol. 2018 Oct;265(10):2353-2362. doi: 10.1007/s00415-018-9008-3. Epub 2018 Aug 16.
• [14] [ARTICLE WITHDRAWN] Downregulation of SRC Kinase Signaling Inhibitor 1 (SRCIN1) Expression by MicroRNA-32 Promotes Proliferation and Epithelial-Mesenchymal Transition in Human Liver Cancer Cells.Oncol Res. 2018 May 7;26(4):573-579. doi: 10.3727/096504017X14954923820137. Epub 2017 May 22.
• [15] MicroRNA-346 functions as an oncogene in cutaneous squamous cell carcinoma.Tumour Biol. 2016 Feb;37(2):2765-71. doi: 10.1007/s13277-015-4046-2. Epub 2015 Sep 26.
• [16] MicroRNA-150-5p and SRC kinase signaling inhibitor 1 involvement in the pathological development of gastric cancer.Exp Ther Med. 2019 Oct;18(4):2667-2674. doi: 10.3892/etm.2019.7828. Epub 2019 Jul 30.
• [17] Hepatitis B virus promotes proliferation and metastasis in male Chinese hepatocellular carcinoma patients through the LEF-1/miR-371a-5p/SRCIN1/pleiotrophin/Slug pathway.Exp Cell Res. 2018 Sep 1;370(1):174-188. doi: 10.1016/j.yexcr.2018.06.020. Epub 2018 Jun 19.
• [18] 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.
• [19] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [20] 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.
• [21] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [22] 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.
• [23] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [24] 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.
• [25] 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.