Details of Drug Off-Target (DOT)

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

DOT Name Protein associated with UVRAG as autophagy enhancer (RUBCNL)
Synonyms Pacer; Protein Rubicon-like
Gene Name RUBCNL
Related Disease
Amyotrophic lateral sclerosis ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cervical Intraepithelial neoplasia ( )
Gastric adenocarcinoma ( )
High blood pressure ( )
Osteoarthritis ( )
Bone osteosarcoma ( )
Neoplasm ( )
Osteosarcoma ( )
UniProt ID
PACER_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF13901 ; PF21054
Sequence
MVSQSTVRQDSPVEPWEGISDHSGIIDGSPRLLNTDHPPCQLDIRLMRHKAVWINPQDVQ
QQPQDLQSQVPAAGNSGTHFVTDAASPSGPSPSCLGDSLAETTLSEDTTDSVGSASPHGS
SEKSSSFSLSSTEVHMVRPGYSHRVSLPTSPGILATSPYPETDSAFFEPSHLTSAADEGA
VQVSRRTISSNSFSPEVFVLPVDVEKENAHFYVADMIISAMEKMKCNILSQQQTESWSKE
VSGLLGSDQPDSEMTFDTNIKQESGSSTSSYSGYEGCAVLQVSPVTETRTYHDVKEICKC
DVDEFVILELGDFNDITETCSCSCSSSKSVTYEPDFNSAELLAKELYRVFQKCWILSVVN
SQLAGSLSAAGSIVVNEECVRKDFESSMNVVQEIKFKSRIRGTEDWAPPRFQIIFNIHPP
LKRDLVVAAQNFFCAGCGTPVEPKFVKRLRYCEYLGKYFCDCCHSYAESCIPARILMMWD
FKKYYVSNFSKQLLDSIWHQPIFNLLSIGQSLYAKAKELDRVKEIQEQLFHIKKLLKTCR
FANSALKEFEQVPGHLTDELHLFSLEDLVRIKKGLLAPLLKDILKASLAHVAGCELCQGK
GFICEFCQNTTVIFPFQTATCRRCSACRACFHKQCFQSSECPRCARITARRKLLESVASA
AT
Function
Regulator of autophagy that promotes autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns(3)P) in late steps of autophagy. Acts by antagonizing RUBCN, thereby stimulating phosphatidylinositol 3-kinase activity of the PI3K/PI3KC3 complex. Following anchorage to the autophagosomal SNARE STX17, promotes the recruitment of PI3K/PI3KC3 and HOPS complexes to the autophagosome to regulate the fusion specificity of autophagosomes with late endosomes/lysosomes. Binds phosphoinositides phosphatidylinositol 3-phosphate (PtdIns(3)P), 4-phosphate (PtdIns(4)P) and 5-phosphate (PtdIns(5)P). In addition to its role in autophagy, acts as a regulator of lipid and glycogen homeostasis. May act as a tumor suppressor (Probable).
Tissue Specificity Expressed weakly in cervical carcinoma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amyotrophic lateral sclerosis DISF7HVM Definitive Biomarker [1]
Cervical cancer DISFSHPF Strong Biomarker [2]
Cervical carcinoma DIST4S00 Strong Biomarker [2]
Cervical Intraepithelial neoplasia DISXP757 Strong Biomarker [3]
Gastric adenocarcinoma DISWWLTC Strong Biomarker [4]
High blood pressure DISY2OHH moderate Biomarker [5]
Osteoarthritis DIS05URM moderate Altered Expression [6]
Bone osteosarcoma DIST1004 Limited Biomarker [7]
Neoplasm DISZKGEW Limited Biomarker [8]
Osteosarcoma DISLQ7E2 Limited Biomarker [7]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 Protein associated with UVRAG as autophagy enhancer (RUBCNL). [9]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [12]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol affects the expression of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [13]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [14]
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⏷ Show the Full List of 6 Drug(s)
2 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 decreases the methylation of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Protein associated with UVRAG as autophagy enhancer (RUBCNL). [16]
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References

1 Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis.Mol Neurodegener. 2019 Mar 27;14(1):14. doi: 10.1186/s13024-019-0313-9.
2 Limited Role of Promoter Methylation of MGMT and C13ORF18 in Triage of Low-Grade Squamous Intraepithelial Lesion.Chin Med J (Engl). 2018 Apr 20;131(8):939-944. doi: 10.4103/0366-6999.229896.
3 C13orf18 and C1orf166 (MULAN) DNA genes methylation are not associated with cervical cancer and precancerous lesions of human papillomavirus genotypes in Iranian women.Asian Pac J Cancer Prev. 2014;15(16):6745-8. doi: 10.7314/apjcp.2014.15.16.6745.
4 Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma.Clin Cancer Res. 2018 Nov 15;24(22):5724-5734. doi: 10.1158/1078-0432.CCR-17-3364. Epub 2018 May 29.
5 Longitudinal Impact of a Park-Based Afterschool Healthy Weight Program on Modifiable Cardiovascular Disease Risk Factors in Youth.J Community Health. 2018 Feb;43(1):103-116. doi: 10.1007/s10900-017-0393-9.
6 LncRNA PACER is down-regulated in osteoarthritis and regulates chondrocyte apoptosis and lncRNA HOTAIR expression.Biosci Rep. 2019 Jun 7;39(6):BSR20190404. doi: 10.1042/BSR20190404. Print 2019 Jun 28.
7 P50-associated COX-2 extragenic RNA (PACER) overexpression promotes proliferation and metastasis of osteosarcoma cells by activating COX-2 gene.Tumour Biol. 2016 Mar;37(3):3879-86. doi: 10.1007/s13277-015-3838-8. Epub 2015 Oct 17.
8 Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation.Mol Ther. 2016 Mar;24(3):536-47. doi: 10.1038/mt.2015.226. Epub 2015 Dec 21.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
11 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
12 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
13 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
14 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.
15 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.
16 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.