Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0EKMVR)

DOT Name AP-4 complex accessory subunit RUSC2 (RUSC2)
Synonyms Interacting protein of Rab1; Iporin; RUN and SH3 domain-containing protein 2
Gene Name RUSC2
Related Disease
Intellectual disability, autosomal recessive 61 ( )
Malignant soft tissue neoplasm ( )
Sarcoma ( )
Intellectual disability ( )
Lung cancer ( )
Lung carcinoma ( )
UniProt ID
RUSC2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6IF2
Pfam ID
PF02759 ; PF07653
Sequence
MDSPPKLTGETLIVHHIPLVHCQVPDRQCCGGAGGGGGSTRPNPFCPPELGITQPDQDLG
QADSLLFSSLHSTPGGTARSIDSTKSRSRDGRGPGAPKRHNPFLLQEGVGEPGLGDLYDD
SIGDSATQQSFHLHGTGQPNFHLSSFQLPPSGPRVGRPWGTTRSRAGVVEGQEQEPVMTL
DTQQCGTSHCCRPELEAETMELDECGGPGGSGSGGGASDTSGFSFDQEWKLSSDESPRNP
GCSGSGDQHCRCSSTSSQSEAADQSMGYVSDSSCNSSDGVLVTFSTLYNKMHGTPRANLN
SAPQSCSDSSFCSHSDPGAFYLDLQPSPFESKMSYESHHPESGGREGGYGCPHASSPELD
ANCNSYRPHCEPCPAVADLTACFQSQARLVVATQNYYKLVTCDLSSQSSPSPAGSSITSC
SEEHTKISPPPGPGPDPGPSQPSEYYLFQKPEVQPEEQEAVSSSTQAAAAVGPTVLEGQV
YTNTSPPNLSTGRQRSRSYDRSLQRSPPVRLGSLERMLSCPVRLSEGPAAMAGPGSPPRR
VTSFAELAKGRKKTGGSGSPPLRVSVGDSSQEFSPIQEAQQDRGAPLDEGTCCSHSLPPM
PLGPGMDLLGPDPSPPWSTQVCQGPHSSEMPPAGLRATGQGPLAQLMDPGPALPGSPANS
HTQRDARARADGGGTESRPVLRYSKEQRPTTLPIQPFVFQHHFPKQLAKARALHSLSQLY
SLSGCSRTQQPAPLAAPAAQVSVPAPSGEPQASTPRATGRGARKAGSEPETSRPSPLGSY
SPIRSVGPFGPSTDSSASTSCSPPPEQPTATESLPPWSHSCPSAVRPATSQQPQKEDQKI
LTLTEYRLHGTGSLPPLGSWRSGLSRAESLARGGGEGSMATRPSNANHLSPQALKWREYR
RKNPLGPPGLSGSLDRRSQEARLARRNPIFEFPGSLSAASHLNCRLNGQAVKPLPLTCPD
FQDPFSLTEKPPAEFCLSPDGSSEAISIDLLQKKGLVKAVNIAVDLIVAHFGTSRDPGVK
AKLGNSSVSPNVGHLVLKYLCPAVRAVLEDGLKAFVLDVIIGQRKNMPWSVVEASTQLGP
STKVLHGLYNKVSQFPELTSHTMRFNAFILGLLNIRSLEFWFNHLYNHEDIIQTHYQPWG
FLSAAHTVCPGLFEELLLLLQPLALLPFSLDLLFQHRLLQSGQQQRQHKELLRVSQDLLL
SAHSTLQLARARGQEGPGDVDRAAQGERVKGVGASEGGEEEEEEEETEEVAEAAGGSGRA
RWARGGQAGWWYQLMQSSQVYIDGSIEGSRFPRGSSNSSSEKKKGAGGGGPPQAPPPREG
VVEGAEACPASEEALGRERGWPFWMGSPPDSVLAELRRSREREGPAASPAENEEGASEPS
PGGIKWGHLFGSRKAQREARPTNRLPSDWLSLDKSMFQLVAQTVGSRREPEPKESLQEPH
SPALPSSPPCEVQALCHHLATGPGQLSFHKGDILRVLGRAGGDWLRCSRGPDSGLVPLAY
VTLTPTPSPTPGSSQN
Function Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network.
Tissue Specificity Widely expressed, with highest levels in brain and testis.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual disability, autosomal recessive 61 DIS5NJ86 Strong Autosomal recessive [1]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [2]
Sarcoma DISZDG3U Strong Biomarker [2]
Intellectual disability DISMBNXP moderate Genetic Variation [1]
Lung cancer DISCM4YA Limited Biomarker [3]
Lung carcinoma DISTR26C Limited Biomarker [3]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of AP-4 complex accessory subunit RUSC2 (RUSC2). [4]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [7]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [8]
Selenium DM25CGV Approved Selenium increases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [9]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [10]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [11]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of AP-4 complex accessory subunit RUSC2 (RUSC2). [12]
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⏷ Show the Full List of 8 Drug(s)

References

1 Loss-of-function mutation in RUSC2 causes intellectual disability and secondary microcephaly. Dev Med Child Neurol. 2016 Dec;58(12):1317-1322. doi: 10.1111/dmcn.13250. Epub 2016 Sep 9.
2 Copy number alterations and neoplasia-specific mutations in MELK, PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias.Genes Chromosomes Cancer. 2014 Jul;53(7):579-88. doi: 10.1002/gcc.22168. Epub 2014 Mar 24.
3 EGF-stimulated activation of Rab35 regulates RUSC2-GIT2 complex formation to stabilize GIT2 during directional lung cancer cell migration.Cancer Lett. 2016 Aug 28;379(1):70-83. doi: 10.1016/j.canlet.2016.05.027. Epub 2016 May 26.
4 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.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
6 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 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.
9 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.
10 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
11 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
12 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.