Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQS91S7)

DOT Name Golgi reassembly-stacking protein 1 (GORASP1)
Synonyms Golgi peripheral membrane protein p65; Golgi phosphoprotein 5; GOLPH5; Golgi reassembly-stacking protein of 65 kDa; GRASP65
Gene Name GORASP1
Related Disease
Lung adenocarcinoma ( )
Melanoma ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Adult T-cell leukemia/lymphoma ( )
Alzheimer disease ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hyperglycemia ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Multiple sclerosis ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Osteosarcoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
Stomach cancer ( )
Systemic lupus erythematosus ( )
T-cell leukaemia ( )
Thyroid cancer ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Glioblastoma multiforme ( )
Squamous cell carcinoma ( )
Thyroid gland carcinoma ( )
Adult glioblastoma ( )
B-cell neoplasm ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
leukaemia ( )
Leukemia ( )
Nasopharyngeal carcinoma ( )
UniProt ID
GORS1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4REY; 6G8T; 6G8W
Pfam ID
PF04495
Sequence
MGLGVSAEQPAGGAEGFHLHGVQENSPAQQAGLEPYFDFIITIGHSRLNKENDTLKALLK
ANVEKPVKLEVFNMKTMRVREVEVVPSNMWGGQGLLGASVRFCSFRRASEQVWHVLDVEP
SSPAALAGLRPYTDYVVGSDQILQESEDFFTLIESHEGKPLKLMVYNSKSDSCREVTVTP
NAAWGGEGSLGCGIGYGYLHRIPTQPPSYHKKPPGTPPPSALPLGAPPPDALPPGPTPED
SPSLETGSRQSDYMEALLQAPGSSMEDPLPGPGSPSHSAPDPDGLPHFMETPLQPPPPVQ
RVMDPGFLDVSGISLLDNSNASVWPSLPSSTELTTTAVSTSGPEDICSSSSSHERGGEAT
WSGSEFEVSFLDSPGAQAQADHLPQLTLPDSLTSAASPEDGLSAELLEAQAEEEPASTEG
LDTGTEAEGLDSQAQISTTE
Function
Key structural protein of the Golgi apparatus. The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon. Acting in concert with GORASP2/GRASP55, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks. However, other studies suggest that GORASP1 plays an important role in assembly and membrane stacking of the cisternae, and in the reassembly of Golgi stacks after breakdown during mitosis. Caspase-mediated cleavage of GORASP1 is required for fragmentation of the Golgi during apoptosis. Also mediates, via its interaction with GOLGA2/GM130, the docking of transport vesicles with the Golgi membranes. Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane.
KEGG Pathway
Autophagy - animal (hsa04140 )
Reactome Pathway
COPII-mediated vesicle transport (R-HSA-204005 )
COPI-mediated anterograde transport (R-HSA-6807878 )
Golgi Cisternae Pericentriolar Stack Reorganization (R-HSA-162658 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung adenocarcinoma DISD51WR Definitive Biomarker [1]
Melanoma DIS1RRCY Definitive Biomarker [2]
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [3]
Adenocarcinoma DIS3IHTY Strong Altered Expression [4]
Adult T-cell leukemia/lymphoma DIS882XU Strong Altered Expression [5]
Alzheimer disease DISF8S70 Strong Biomarker [6]
Bladder cancer DISUHNM0 Strong Biomarker [7]
Bone osteosarcoma DIST1004 Strong Altered Expression [8]
Breast cancer DIS7DPX1 Strong Biomarker [9]
Breast carcinoma DIS2UE88 Strong Biomarker [9]
Carcinoma DISH9F1N Strong Altered Expression [10]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [11]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [12]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [13]
Gastric cancer DISXGOUK Strong Biomarker [14]
Glioma DIS5RPEH Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
Hyperglycemia DIS0BZB5 Strong Biomarker [17]
Lung cancer DISCM4YA Strong Altered Expression [18]
Lung carcinoma DISTR26C Strong Altered Expression [18]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [19]
Multiple sclerosis DISB2WZI Strong Altered Expression [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [22]
Osteoarthritis DIS05URM Strong Biomarker [23]
Osteosarcoma DISLQ7E2 Strong Altered Expression [8]
Prostate cancer DISF190Y Strong Biomarker [24]
Prostate carcinoma DISMJPLE Strong Biomarker [24]
Rheumatoid arthritis DISTSB4J Strong Biomarker [25]
Stomach cancer DISKIJSX Strong Biomarker [14]
Systemic lupus erythematosus DISI1SZ7 Strong Posttranslational Modification [26]
T-cell leukaemia DISJ6YIF Strong Altered Expression [5]
Thyroid cancer DIS3VLDH Strong Posttranslational Modification [27]
Ulcerative colitis DIS8K27O Strong Biomarker [28]
Urinary bladder cancer DISDV4T7 Strong Biomarker [7]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [7]
Glioblastoma multiforme DISK8246 moderate Biomarker [29]
Squamous cell carcinoma DISQVIFL moderate Biomarker [30]
Thyroid gland carcinoma DISMNGZ0 moderate Posttranslational Modification [27]
Adult glioblastoma DISVP4LU Limited Biomarker [31]
B-cell neoplasm DISVY326 Limited Altered Expression [32]
Cervical cancer DISFSHPF Limited Biomarker [33]
Cervical carcinoma DIST4S00 Limited Biomarker [33]
Colon cancer DISVC52G Limited Altered Expression [34]
Colon carcinoma DISJYKUO Limited Altered Expression [34]
leukaemia DISS7D1V Limited Posttranslational Modification [35]
Leukemia DISNAKFL Limited Posttranslational Modification [35]
Nasopharyngeal carcinoma DISAOTQ0 Limited Altered Expression [36]
------------------------------------------------------------------------------------
⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Golgi reassembly-stacking protein 1 (GORASP1). [37]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Golgi reassembly-stacking protein 1 (GORASP1). [38]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Golgi reassembly-stacking protein 1 (GORASP1). [37]
Selenium DM25CGV Approved Selenium increases the expression of Golgi reassembly-stacking protein 1 (GORASP1). [39]
------------------------------------------------------------------------------------
2 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 decreases the phosphorylation of Golgi reassembly-stacking protein 1 (GORASP1). [40]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Golgi reassembly-stacking protein 1 (GORASP1). [40]
------------------------------------------------------------------------------------

References

1 Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-B Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF- and the Fas Ligand.Int J Mol Sci. 2017 Dec 2;18(12):2603. doi: 10.3390/ijms18122603.
2 ABCB5 promotes melanoma metastasis through enhancing NF-B p65 protein stability.Biochem Biophys Res Commun. 2017 Oct 7;492(1):18-26. doi: 10.1016/j.bbrc.2017.08.052. Epub 2017 Aug 15.
3 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
4 Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma.Histopathology. 2007 May;50(6):720-6. doi: 10.1111/j.1365-2559.2007.02675.x.
5 Detection of human T lymphotropic virus type-I bZIP factor and tax in the salivary glands of Sjgren's syndrome patients.Clin Exp Rheumatol. 2018 May-Jun;36 Suppl 112(3):51-60. Epub 2018 Mar 20.
6 Network-Driven Proteogenomics Unveils an Aging-Related Imbalance in the Olfactory IB-NFB p65 Complex Functionality in Tg2576 Alzheimer's Disease Mouse Model.Int J Mol Sci. 2017 Oct 27;18(11):2260. doi: 10.3390/ijms18112260.
7 Protein kinase C- (PKC) modulates cell apoptosis by stimulating nuclear translocation of NF-kappa-B p65 in urothelial cell carcinoma of the bladder.BMC Cancer. 2017 Jun 19;17(1):432. doi: 10.1186/s12885-017-3401-7.
8 P65-mediated miR-590 inhibition modulates the chemoresistance of osteosarcoma to doxorubicin through targeting wild-type p53-induced phosphatase 1.J Cell Biochem. 2019 Apr;120(4):5652-5665. doi: 10.1002/jcb.27849. Epub 2018 Nov 1.
9 Salinomycin reduces growth, proliferation and metastasis of cisplatin resistant breast cancer cells via NF-kB deregulation.Toxicol In Vitro. 2019 Oct;60:125-133. doi: 10.1016/j.tiv.2019.05.004. Epub 2019 May 8.
10 ER regulation of NF-kB activation in prostate cancer is mediated by HIF-1.Oncotarget. 2015 Nov 24;6(37):40247-54. doi: 10.18632/oncotarget.5377.
11 Activation of EMT in colorectal cancer by MTDH/NF-B p65 pathway.Mol Cell Biochem. 2019 Jul;457(1-2):83-91. doi: 10.1007/s11010-019-03514-x. Epub 2019 Mar 1.
12 Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells.PLoS One. 2019 Nov 26;14(11):e0225450. doi: 10.1371/journal.pone.0225450. eCollection 2019.
13 Targeting TRIM3 deletion-induced tumor-associated lymphangiogenesis prohibits lymphatic metastasis in esophageal squamous cell carcinoma.Oncogene. 2019 Apr;38(15):2736-2749. doi: 10.1038/s41388-018-0621-5. Epub 2018 Dec 12.
14 miR-155-5p inhibition promotes the transition of bone marrow mesenchymal stem cells to gastric cancer tissue derived MSC-like cells via NF-B p65 activation.Oncotarget. 2016 Mar 29;7(13):16567-80. doi: 10.18632/oncotarget.7767.
15 Molecular functions of brain expressed X-linked 2 (BEX2) in malignancies.Exp Cell Res. 2019 Mar 15;376(2):221-226. doi: 10.1016/j.yexcr.2019.02.014. Epub 2019 Feb 16.
16 Mesencephalic Astrocyte-Derived Neurotrophic Factor Inhibits Liver Cancer Through Small Ubiquitin-Related Modifier (SUMO)ylation-Related Suppression of NF-B/Snail Signaling Pathway and Epithelial-Mesenchymal Transition.Hepatology. 2020 Apr;71(4):1262-1278. doi: 10.1002/hep.30917. Epub 2020 Jan 26.
17 Panax notoginseng Saponins Regulate Macrophage Polarization under Hyperglycemic Condition via NF-B Signaling Pathway.Biomed Res Int. 2018 Jul 30;2018:9239354. doi: 10.1155/2018/9239354. eCollection 2018.
18 T cell factor-4 functions as a co-activator to promote NF-B-dependent MMP-15 expression in lung carcinoma cells.Sci Rep. 2016 Apr 5;6:24025. doi: 10.1038/srep24025.
19 Cleaved caspase-3 and nuclear factor-kappaB p65 are prognostic factors in metastatic serous ovarian carcinoma.Hum Pathol. 2009 Jun;40(6):795-806. doi: 10.1016/j.humpath.2008.10.019. Epub 2009 Jan 20.
20 A detrimental role of RelB in mature oligodendrocytes during experimental acute encephalomyelitis.J Neuroinflammation. 2019 Jul 30;16(1):161. doi: 10.1186/s12974-019-1548-7.
21 p65/miR-23a/CCL22 axis regulated regulatory T cells recruitment in hepatitis B virus positive hepatocellular carcinoma.Cancer Med. 2020 Jan;9(2):711-723. doi: 10.1002/cam4.2611. Epub 2019 Nov 25.
22 Eugenol inhibits non-small cell lung cancer by repressing expression of NF-B-regulated TRIM59.Phytother Res. 2019 May;33(5):1562-1569. doi: 10.1002/ptr.6352. Epub 2019 Apr 1.
23 Dexmedetomidine inhibits the NF-B pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats.Pharm Biol. 2019 Dec;57(1):649-659. doi: 10.1080/13880209.2019.1651874.
24 Validation of the prognostic value of NF-B p65 in prostate cancer: A retrospective study using a large multi-institutional cohort of the Canadian Prostate Cancer Biomarker Network.PLoS Med. 2019 Jul 2;16(7):e1002847. doi: 10.1371/journal.pmed.1002847. eCollection 2019 Jul.
25 Down-regulation of microRNA-142-3p inhibits the aggressive phenotypes of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting nuclear factor-B signaling.Biosci Rep. 2019 Jul 8;39(7):BSR20190700. doi: 10.1042/BSR20190700. Print 2019 Jul 31.
26 Deficiency in IRAK4 activity attenuates manifestations of murine Lupus.Eur J Immunol. 2017 May;47(5):880-891. doi: 10.1002/eji.201646641. Epub 2017 Mar 31.
27 AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer.Cancers (Basel). 2019 Jun 7;11(6):785. doi: 10.3390/cancers11060785.
28 Activation of adenosine A3 receptor inhibits inflammatory cytokine production in colonic mucosa of patients with ulcerative colitis by down-regulating the nuclear factor-kappa B signaling.J Dig Dis. 2020 Jan;21(1):38-45. doi: 10.1111/1751-2980.12831. Epub 2019 Dec 17.
29 A novel NFIA-NFB feed-forward loop contributes to glioblastoma cell survival.Neuro Oncol. 2017 Apr 1;19(4):524-534. doi: 10.1093/neuonc/now233.
30 Epstein-Barr virus-encoded EBNA1 inhibits the canonical NF-kappaB pathway in carcinoma cells by inhibiting IKK phosphorylation.Mol Cancer. 2010 Jan 5;9:1. doi: 10.1186/1476-4598-9-1.
31 Tumor suppressors microRNA-302d and microRNA-16 inhibit human glioblastoma multiforme by targeting NF-B and FGF2.Mol Biosyst. 2017 Jun 27;13(7):1345-1354. doi: 10.1039/c7mb00139h.
32 Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion.Neural Regen Res. 2019 May;14(5):783-793. doi: 10.4103/1673-5374.249226.
33 Synchronous coexpression of Id? and nuclear NFB p65 promotes cervical cancer progression and malignancy, and is associated with a poor prognosis and chemosensitivity.Oncol Rep. 2019 Nov;42(5):2075-2086. doi: 10.3892/or.2019.7301. Epub 2019 Sep 5.
34 PHD2 exerts anti-cancer and anti-inflammatory effects in colon cancer xenografts mice via attenuating NF-B activity.Life Sci. 2020 Feb 1;242:117167. doi: 10.1016/j.lfs.2019.117167. Epub 2019 Dec 12.
35 The Marine Natural Product Pseudopterosin Blocks Cytokine Release of Triple-Negative Breast Cancer and Monocytic Leukemia Cells by Inhibiting NF-B Signaling.Mar Drugs. 2017 Aug 23;15(9):262. doi: 10.3390/md15090262.
36 The anti-tumor function of the IKK inhibitor PS1145 and high levels of p65 and KLF4 are associated with the drug resistance in nasopharyngeal carcinoma cells.Sci Rep. 2019 Aug 19;9(1):12064. doi: 10.1038/s41598-019-48590-7.
37 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
38 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.
39 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
40 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.