Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3X4606)

DOT Name Guanine nucleotide exchange factor subunit RIC1 (RIC1)
Synonyms Connexin-43-interacting protein of 150 kDa; Protein RIC1 homolog; RAB6A-GEF complex partner protein 1
Gene Name RIC1
Related Disease
Cataract ( )
Cleft lip/palate ( )
Small-cell lung cancer ( )
Catifa syndrome ( )
UniProt ID
RIC1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF07064
Sequence
MYFLSGWPKRLLCPLGSPAEAPFHVQSDPQRAFFAVLAAARLSIWYSRPSVLIVTYKEPA
KSSTQFGSYKQAEWRPDSTMIAVSTANGYILFFHITSTRGDKYLYEPVYPKGSPQMKGTP
HFKEEQCAPALNLEMRKILDLQAPIMSLQSVLEDLLVATSDGLLHLIHWEGMTNGRKAIN
LCTVPFSVDLQSSRVGSFLGFTDVHIRDMEYCATLDGFAVVFNDGKVGFITPVSSRFTAE
QLHGVWPQDVVDGTCVAVNNKYRLMAFGCVSGSVQVYTIDNSTGAMLLSHKLELTAKQYP
DIWNKTGAVKLMRWSPDNSVVIVTWEYGGLSLWSVFGAQLICTLGGDFAYRSDGTKKDPL
KINSMSWGAEGYHLWVISGFGSQNTEIESDLRSVVKQPSILLFQFIKSVLTVNPCMSNQE
QVLLQGEDRLYLNCGEASQTQNPRSSSTHSEHKPSREKSPFADGGLESQGLSTLLGHRHW
HVVQISSTYLESNWPIRFSAIDKLGQNIAVVGKFGFAHYSLLTKKWKLFGNITQEQNMIV
TGGLAWWNDFMVLACYNINDRQEELRVYLRTSNLDNAFAHVTKAQAETLLLSVFQDMVIV
FRADCSICLYSIERKSDGPNTTAGIQVLQEVSMSRYIPHPFLVVSVTLTSVSTENGITLK
MPQQARGAESIMLNLAGQLIMMQRDRSGPQIREKDSNPNNQRKLLPFCPPVVLAQSVENV
WTTCRANKQKRHLLEALWLSCGGAGMKVWLPLFPRDHRKPHSFLSQRIMLPFHINIYPLA
VLFEDALVLGAVNDTLLYDSLYTRNNAREQLEVLFPFCVVERTSQIYLHHILRQLLVRNL
GEQALLLAQSCATLPYFPHVLELMLHEVLEEEATSREPIPDPLLPTVAKFITEFPLFLQT
VVHCARKTEYALWNYLFAAVGNPKDLFEECLMAQDLDTAASYLIILQNMEVPAVSRQHAT
LLFNTALEQGKWDLCRHMIRFLKAIGSGESETPPSTPTAQEPSSSGGFEFFRNRSISLSQ
SAENVPASKFSLQKTLSMPSGPSGKRWSKDSDCAENMYIDMMLWRHARRLLEDVRLKDLG
CFAAQLGFELISWLCKERTRAARVDNFVIALKRLHKDFLWPLPIIPASSISSPFKNGKYR
TVGEQLLKSQSADPFLNLEMDAGISNIQRSQSWLSNIGPTHHEIDTASSHGPQMQDAFLS
PLSNKGDECSIGSATDLTESSSMVDGDWTMVDENFSTLSLTQSELEHISMELASKGPHKS
QVQLRYLLHIFMEAGCLDWCIVIGLILRESSIINQILVITQSSEVDGEMLQNIKTGLHAV
DRWASTDCPGYKPFLNIIKPQLQKLSEITEEQVQPDAFQPITMGKTPEQTSPRAEESRGS
SSHGSIPQGEVGSSNMVSRKEEDTAQAEEEEPFQDGTYDCSVS
Function
The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP, and may thereby be required for efficient fusion of endosome-derived vesicles with the Golgi compartment. The RIC1-RGP1 complex participates in the recycling of mannose-6-phosphate receptors. Required for phosphorylation and localization of GJA1. Is a regulator of procollagen transport and secretion, and is required for correct cartilage morphogenesis and development of the craniofacial skeleton.
Tissue Specificity Present in kidney and various cell lines (at protein level). Widely expressed at low level.
Reactome Pathway
Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440 )
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
Intra-Golgi traffic (R-HSA-6811438 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cataract DISUD7SL Strong Genetic Variation [1]
Cleft lip/palate DIS14IG3 Strong Genetic Variation [1]
Small-cell lung cancer DISK3LZD moderate Altered Expression [2]
Catifa syndrome DIS72FE1 Limited Autosomal recessive [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [5]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [6]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [7]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [9]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [10]
crotylaldehyde DMTWRQI Investigative crotylaldehyde decreases the expression of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [11]
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⏷ Show the Full List of 7 Drug(s)
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 decreases the phosphorylation of Guanine nucleotide exchange factor subunit RIC1 (RIC1). [8]
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References

1 Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.Hum Genet. 2017 Feb;136(2):205-225. doi: 10.1007/s00439-016-1747-6. Epub 2016 Nov 22.
2 Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer.Genes Chromosomes Cancer. 2013 Sep;52(9):802-16. doi: 10.1002/gcc.22076. Epub 2013 May 28.
3 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.
4 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.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
7 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
8 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.
9 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.
10 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
11 Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.