Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJAMS3)

• DOT Name: Caprin-1 (CAPRIN1)
• Synonyms: Cell cycle-associated protein 1; Cytoplasmic activation- and proliferation-associated protein 1; GPI-anchored membrane protein 1; GPI-anchored protein p137; GPI-p137; p137GPI; Membrane component chromosome 11 surface marker 1; RNA granule protein 105
• Gene Name: CAPRIN1
• Related Disease:
  Bone osteosarcoma
  Clear cell renal carcinoma
  Dengue
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Zika virus infection
  CHARGE syndrome
  Cognitive impairment
  Epilepsy
  Fragile X syndrome
  Hepatocellular carcinoma
  Advanced cancer
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: CAPR1_HUMAN
• PDB ID: 4WBE; 4WBP; 6TA7; 7XHG
• Pfam ID: PF12287 ; PF18293
• Sequence:
  MPSATSHSGSGSKSSGPPPPSGSSGSEAAAGAGAAAPASQHPATGTGAVQTEAMKQILGV
  IDKKLRNLEKKKGKLDDYQERMNKGERLNQDQLDAVSKYQEVTNNLEFAKELQRSFMALS
  QDIQKTIKKTARREQLMREEAEQKRLKTVLELQYVLDKLGDDEVRTDLKQGLNGVPILSE
  EELSLLDEFYKLVDPERDMSLRLNEQYEHASIHLWDLLEGKEKPVCGTTYKVLKEIVERV
  FQSNYFDSTHNHQNGLCEEEEAASAPAVEDQVPEAEPEPAEEYTEQSEVESTEYVNRQFM
  AETQFTSGEKEQVDEWTVETVEVVNSLQQQPQAASPSVPEPHSLTPVAQADPLVRRQRVQ
  DLMAQMQGPYNFIQDSMLDFENQTLDPAIVSAQPMNPTQNMDMPQLVCPPVHSESRLAQP
  NQVPVQPEATQVPLVSSTSEGYTASQPLYQPSHATEQRPQKEPIDQIQATISLNTDQTTA
  SSSLPAASQPQVFQAGTSKPLHSSGINVNAAPFQSMQTVFNMNAPVPPVNEPETLKQQNQ
  YQASYNQSFSSQPHQVEQTELQQEQLQTVVGTYHGSPDQSHQVTGNHQQPPQQNTGFPRS
  NQPYYNSRGVSRGGSRGARGLMNGYRGPANGFRGGYDGYRPSFSNTPNSGYTQSQFSAPR
  DYSGYQRDGYQQNFKRGSGQSGPRGAPRGRGGPPRPNRGMPQMNTQQVN
• Function: mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in synaptic plasticity in neurons and cell proliferation and migration in multiple cell types. Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors. Undergoes liquid-liquid phase separation following phosphorylation and interaction with FMR1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs. In these cytoplasmic ribonucleoprotein granules, CAPRIN1 mediates recruitment of CNOT7 deadenylase, leading to mRNA deadenylation and degradation. Binds directly and selectively to MYC and CCND2 mRNAs. In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Dengue	DISKH221	Strong	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[5]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[5]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[6]
Zika virus infection	DISQUCTY	Strong	Biomarker	[7]
CHARGE syndrome	DISKD3CW	moderate	Biomarker	[8]
Cognitive impairment	DISH2ERD	moderate	Biomarker	[8]
Epilepsy	DISBB28L	moderate	Biomarker	[8]
Fragile X syndrome	DISE8W3A	moderate	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[9]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[11]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[11]

18 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 Caprin-1 (CAPRIN1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Caprin-1 (CAPRIN1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Caprin-1 (CAPRIN1).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Caprin-1 (CAPRIN1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Caprin-1 (CAPRIN1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Caprin-1 (CAPRIN1).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Caprin-1 (CAPRIN1).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Caprin-1 (CAPRIN1).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Caprin-1 (CAPRIN1).	[20]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Caprin-1 (CAPRIN1).	[21]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Caprin-1 (CAPRIN1).	[22]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Caprin-1 (CAPRIN1).	[23]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Caprin-1 (CAPRIN1).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Caprin-1 (CAPRIN1).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Caprin-1 (CAPRIN1).	[24]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Caprin-1 (CAPRIN1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Caprin-1 (CAPRIN1).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Caprin-1 (CAPRIN1).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Caprin-1 (CAPRIN1).	[25]

References

• [1] Caprin-1, a novel Cyr61-interacting protein, promotes osteosarcoma tumor growth and lung metastasis in mice.Biochim Biophys Acta. 2013 Aug;1832(8):1173-82. doi: 10.1016/j.bbadis.2013.03.014. Epub 2013 Mar 23.
• [2] MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis.Oncotarget. 2015 May 30;6(15):13201-15. doi: 10.18632/oncotarget.3915.
• [3] Correction: G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA.PLoS Pathog. 2017 Mar 28;13(3):e1006295. doi: 10.1371/journal.ppat.1006295. eCollection 2017 Mar.
• [4] Upregulation of caprin1 expression is associated with poor prognosis in hepatocellular carcinoma.Pathol Res Pract. 2017 Dec;213(12):1563-1567. doi: 10.1016/j.prp.2017.07.014. Epub 2017 Jul 15.
• [5] Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly.Mol Cancer. 2019 Nov 26;18(1):170. doi: 10.1186/s12943-019-1096-x.
• [6] Tylophorine-based compounds are therapeutic in rheumatoid arthritis by targeting the caprin-1 ribonucleoprotein complex and inhibiting expression of associated c-Myc and HIF-1.Pharmacol Res. 2020 Feb;152:104581. doi: 10.1016/j.phrs.2019.104581. Epub 2019 Nov 30.
• [7] Zika Virus Hijacks Stress Granule Proteins and Modulates the Host Stress Response.J Virol. 2017 Jul 27;91(16):e00474-17. doi: 10.1128/JVI.00474-17. Print 2017 Aug 15.
• [8] Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.Am J Hum Genet. 2013 Aug 8;93(2):249-63. doi: 10.1016/j.ajhg.2013.06.012. Epub 2013 Jul 11.
• [9] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [10] Caprin-1 is a novel microRNA-223 target for regulating the proliferation and invasion of human breast cancer cells.Biomed Pharmacother. 2013 Sep;67(7):629-36. doi: 10.1016/j.biopha.2013.06.006. Epub 2013 Jul 12.
• [11] MicroRNA-181a Functions as an Oncogene in Gastric Cancer by Targeting Caprin-1.Front Pharmacol. 2019 Jan 10;9:1565. doi: 10.3389/fphar.2018.01565. eCollection 2018.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] 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.
• [20] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [21] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [22] Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder in vascular endothelial cells and colon cancer cells. Chemosphere. 2016 Jun;153:75-7. doi: 10.1016/j.chemosphere.2015.12.085. Epub 2016 Mar 21.
• [23] Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
• [24] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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.
• [26] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [27] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [28] 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.