Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1A1ZXH)

DOT Name Coiled-coil domain-containing protein 22 (CCDC22)
Gene Name CCDC22
Related Disease
Autoimmune disease ( )
Endometriosis ( )
Neoplasm ( )
Rigid spine muscular dystrophy 1 ( )
Ritscher-Schinzel syndrome 2 ( )
Silver-Russell syndrome ( )
Systemic lupus erythematosus ( )
Intellectual disability ( )
Ritscher-Schinzel syndrome ( )
Pneumonia ( )
UniProt ID
CCD22_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8F2U
Pfam ID
PF05667 ; PF21674
Sequence
MEEADRILIHSLRQAGTAVPPDVQTLRAFTTELVVEAVVRCLRVINPAVGSGLSPLLPLA
MSARFRLAMSLAQACMDLGYPLELGYQNFLYPSEPDLRDLLLFLAERLPTDASEDADQPA
GDSAILLRAIGSQIRDQLALPWVPPHLRTPKLQHLQGSALQKPFHASRLVVPELSSRGEP
REFQASPLLLPVPTQVPQPVGRVASLLEHHALQLCQQTGRDRPGDEDWVHRTSRLPPQED
TRAQRQRLQKQLTEHLRQSWGLLGAPIQARDLGELLQAWGAGAKTGAPKGSRFTHSEKFT
FHLEPQAQATQVSDVPATSRRPEQVTWAAQEQELESLREQLEGVNRSIEEVEADMKTLGV
SFVQAESECRHSKLSTAEREQALRLKSRAVELLPDGTANLAKLQLVVENSAQRVIHLAGQ
WEKHRVPLLAEYRHLRKLQDCRELESSRRLAEIQELHQSVRAAAEEARRKEEVYKQLMSE
LETLPRDVSRLAYTQRILEIVGNIRKQKEEITKILSDTKELQKEINSLSGKLDRTFAVTD
ELVFKDAKKDDAVRKAYKYLAALHENCSQLIQTIEDTGTIMREVRDLEEQIETELGKKTL
SNLEKIREDYRALRQENAGLLGRVREA
Function
Involved in regulation of NF-kappa-B signaling. Promotes ubiquitination of I-kappa-B-kinase subunit IKBKB and its subsequent proteasomal degradation leading to NF-kappa-B activation; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. May down-regulate NF-kappa-B activity via association with COMMD1 and involving a CUL2-dependent E3 ubiquitin ligase complex. Regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10. Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1. Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes ; (Microbial infection) The CCC complex, in collaboration with the heterotrimeric retriever complex, mediates the exit of human papillomavirus to the cell surface.
Tissue Specificity Widely expressed in adult tissues and in fetal liver and brain, with highest levels in prostate and lowest in skeletal muscle.
Reactome Pathway
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autoimmune disease DISORMTM Strong Genetic Variation [1]
Endometriosis DISX1AG8 Strong Genetic Variation [2]
Neoplasm DISZKGEW Strong Genetic Variation [3]
Rigid spine muscular dystrophy 1 DISHZE8T Strong Genetic Variation [4]
Ritscher-Schinzel syndrome 2 DISMDVMV Strong X-linked [5]
Silver-Russell syndrome DISSVJ1D Strong Genetic Variation [4]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [1]
Intellectual disability DISMBNXP moderate Genetic Variation [4]
Ritscher-Schinzel syndrome DIS5TSUC Supportive Autosomal recessive [4]
Pneumonia DIS8EF3M Limited Genetic Variation [6]
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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
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Coiled-coil domain-containing protein 22 (CCDC22). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Coiled-coil domain-containing protein 22 (CCDC22). [11]
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6 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 Coiled-coil domain-containing protein 22 (CCDC22). [8]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Coiled-coil domain-containing protein 22 (CCDC22). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Coiled-coil domain-containing protein 22 (CCDC22). [10]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of Coiled-coil domain-containing protein 22 (CCDC22). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Coiled-coil domain-containing protein 22 (CCDC22). [12]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Coiled-coil domain-containing protein 22 (CCDC22). [13]
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⏷ Show the Full List of 6 Drug(s)

References

1 Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases with focus on systemic lupus erythematosus.Immunol Lett. 2017 Jan;181:58-62. doi: 10.1016/j.imlet.2016.11.011. Epub 2016 Nov 22.
2 CCDC22 gene polymorphism is associated with advanced stages of endometriosis in a sample of Brazilian women.J Assist Reprod Genet. 2017 Jul;34(7):939-944. doi: 10.1007/s10815-017-0936-0. Epub 2017 May 4.
3 Identification of a novel CCDC22 mutation in a patient with severe Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and aggressive natural killer cell leukemia.Int J Hematol. 2019 Jun;109(6):744-750. doi: 10.1007/s12185-019-02595-0. Epub 2019 Jan 31.
4 Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome. Eur J Hum Genet. 2015 May;23(5):633-8. doi: 10.1038/ejhg.2014.109. Epub 2014 Jun 11.
5 CCDC22: a novel candidate gene for syndromic X-linked intellectual disability. Mol Psychiatry. 2012 Jan;17(1):4-7. doi: 10.1038/mp.2011.95. Epub 2011 Aug 9.
6 FOXP3 rs3761548 polymorphism is associated with tacrolimus-induced acute nephrotoxicity in renal transplant patients.Eur J Clin Pharmacol. 2017 Jan;73(1):39-47. doi: 10.1007/s00228-016-2140-z. Epub 2016 Oct 17.
7 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.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 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.
10 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.
11 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.
12 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
13 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.