Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB4AD3V)

DOT Name E3 ubiquitin-protein ligase CBLL2 (CBLL2)
Synonyms EC 2.3.2.27; Cbl proto-oncogene-like protein 2; RING-type E3 ubiquitin transferase ZNF645; Zinc finger protein 645; c-Cbl-like protein 2
Gene Name CBLL2
Related Disease
Endometrial carcinoma ( )
Lafora disease ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Adult lymphoma ( )
Angelman syndrome ( )
Autism ( )
Autoimmune disease ( )
Cerebellar ataxia ( )
Charcot marie tooth disease ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Fanconi anemia complementation group A ( )
Fanconi's anemia ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Herpes simplex infection ( )
Intellectual disability ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Neurodevelopmental disorder ( )
Non-small-cell lung cancer ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Parkinson disease ( )
Pediatric lymphoma ( )
Plasma cell myeloma ( )
Prion disease ( )
Renal cell carcinoma ( )
Small lymphocytic lymphoma ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Urinary bladder neoplasm ( )
Von hippel-lindau disease ( )
Young-onset Parkinson disease ( )
Autosomal recessive juvenile Parkinson disease 2 ( )
Breast neoplasm ( )
Clear cell renal carcinoma ( )
Liver cirrhosis ( )
Melanoma ( )
Rheumatoid arthritis ( )
Triple negative breast cancer ( )
UniProt ID
CBLL2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
2.3.2.27
Pfam ID
PF18408
Sequence
MNKMPAGEQECEYNKEGKYYSKGVKLVRKKKKIPGYRWGDIKINIIGEKDDLPIHFCDKC
DLPIKIYGRIIPCKHAFCYHCANLYDKVGYKVCPRCRYPVLRIEAHKRGSVFMCSIVQQC
KRTYLSQKSLQAHIKRRHKRARKQVTSASLEKVRPHIAPPQTEISDIPKRLQDRDHLSYI
PPEQHTMVSLPSVQHMLQEQHNQPHKDIQAPPPELSLSLPFPIQWETVSIFTRKHGNLTV
DHIQNNSDSGAKKPTPPDYYPECQSQPAVSSPHHIIPQKQHYAPPPSPSSPVNHQMPYPP
QDVVTPNSVRSQVPALTTTYDPSSGYIIVKVPPDMNSPPLRAPQSQNGNPSASEFASHHY
NLNILPQFTENQETLSPQFTQTDAMDHRRWPAWKRLSPCPPTRSPPPSTLHGRSHHSHQR
RHRRY
Function E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. May operate on tyrosine-phosphorylated SRC substrates.
Tissue Specificity Exclusively expressed in testis and sperm, including spermatocytes, round and elongated spermatids, and Leydig cells.
Reactome Pathway
Antigen processing (R-HSA-983168 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Endometrial carcinoma DISXR5CY Definitive Genetic Variation [1]
Lafora disease DIS83JHH Definitive Biomarker [2]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [3]
Adult glioblastoma DISVP4LU Strong Altered Expression [4]
Adult lymphoma DISK8IZR Strong Altered Expression [5]
Angelman syndrome DIS4QVXO Strong Genetic Variation [6]
Autism DISV4V1Z Strong Genetic Variation [7]
Autoimmune disease DISORMTM Strong Altered Expression [8]
Cerebellar ataxia DIS9IRAV Strong Biomarker [9]
Charcot marie tooth disease DIS3BT2L Strong Genetic Variation [10]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [11]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [12]
Fanconi anemia complementation group A DIS8PZLI Strong Biomarker [13]
Fanconi's anemia DISGW6Q8 Strong Biomarker [13]
Gastric cancer DISXGOUK Strong Biomarker [14]
Glioblastoma multiforme DISK8246 Strong Altered Expression [4]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
Herpes simplex infection DISL1SAV Strong Biomarker [17]
Intellectual disability DISMBNXP Strong Genetic Variation [18]
Liver cancer DISDE4BI Strong Biomarker [19]
Lung cancer DISCM4YA Strong Altered Expression [20]
Lung carcinoma DISTR26C Strong Altered Expression [20]
Lymphoma DISN6V4S Strong Altered Expression [5]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [21]
Neoplasm DISZKGEW Strong Genetic Variation [22]
Neurodevelopmental disorder DIS372XH Strong Genetic Variation [23]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [24]
Obesity DIS47Y1K Strong Biomarker [25]
Ovarian cancer DISZJHAP Strong Biomarker [12]
Ovarian neoplasm DISEAFTY Strong Biomarker [12]
Pancreatic cancer DISJC981 Strong Altered Expression [26]
Parkinson disease DISQVHKL Strong Altered Expression [27]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [5]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [28]
Prion disease DISOUMB0 Strong Biomarker [29]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [30]
Small lymphocytic lymphoma DIS30POX Strong Genetic Variation [31]
Stomach cancer DISKIJSX Strong Biomarker [14]
Type-1/2 diabetes DISIUHAP Strong Genetic Variation [32]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [33]
Von hippel-lindau disease DIS6ZFQQ Strong Biomarker [34]
Young-onset Parkinson disease DIS05LFS Strong Genetic Variation [35]
Autosomal recessive juvenile Parkinson disease 2 DISNSTD1 Limited Altered Expression [36]
Breast neoplasm DISNGJLM Limited Altered Expression [37]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [38]
Liver cirrhosis DIS4G1GX Limited Biomarker [25]
Melanoma DIS1RRCY Limited Biomarker [39]
Rheumatoid arthritis DISTSB4J Limited Biomarker [40]
Triple negative breast cancer DISAMG6N Limited Biomarker [41]
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⏷ Show the Full List of 50 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Permethrin DMZ0Q1G Approved Permethrin increases the expression of E3 ubiquitin-protein ligase CBLL2 (CBLL2). [42]
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References

1 CRL3-SPOP ubiquitin ligase complex suppresses the growth of diffuse large B-cell lymphoma by negatively regulating the MyD88/NF-B signaling.Leukemia. 2020 May;34(5):1305-1314. doi: 10.1038/s41375-019-0661-z. Epub 2019 Nov 27.
2 Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease.Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118613. doi: 10.1016/j.bbamcr.2019.118613. Epub 2019 Nov 21.
3 Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia.Cancers (Basel). 2019 Nov 3;11(11):1717. doi: 10.3390/cancers11111717.
4 TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.Biochim Biophys Acta Gen Subj. 2019 Feb;1863(2):491-501. doi: 10.1016/j.bbagen.2018.12.001. Epub 2018 Dec 5.
5 Activation of MET signaling by HDAC6 offers a rationale for a novel ricolinostat and crizotinib combinatorial therapeutic strategy in diffuse large B-cell lymphoma.J Pathol. 2018 Oct;246(2):141-153. doi: 10.1002/path.5108. Epub 2018 Aug 20.
6 A bipartite boundary element restricts UBE3A imprinting to mature neurons.Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2181-2186. doi: 10.1073/pnas.1815279116. Epub 2019 Jan 23.
7 Behavioral, circuitry, and molecular aberrations by region-specific deficiency of the high-risk autism gene Cul3.Mol Psychiatry. 2021 May;26(5):1491-1504. doi: 10.1038/s41380-019-0498-x. Epub 2019 Aug 27.
8 The E3 ubiquitin ligase Itch restricts antigen-driven B cell responses.J Exp Med. 2019 Sep 2;216(9):2170-2183. doi: 10.1084/jem.20181953. Epub 2019 Jul 16.
9 RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy.Front Endocrinol (Lausanne). 2019 Jan 24;10:12. doi: 10.3389/fendo.2019.00012. eCollection 2019.
10 LRSAM1-mediated ubiquitylation is disrupted in axonal Charcot-Marie-Tooth disease 2P.Hum Mol Genet. 2017 Jun 1;26(11):2034-2041. doi: 10.1093/hmg/ddx089.
11 TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/-catenin degradation and is targeted for GSK3B/GSK3-mediated phosphorylation and degradation.Autophagy. 2019 Sep;15(9):1506-1522. doi: 10.1080/15548627.2019.1586250. Epub 2019 Mar 4.
12 Cul4 E3 ubiquitin ligase regulates ovarian cancer drug resistance by targeting the antiapoptotic protein BIRC3.Cell Death Dis. 2019 Feb 4;10(2):104. doi: 10.1038/s41419-018-1200-y.
13 High expression of UBE2T predicts poor prognosis and survival in multiple myeloma.Cancer Gene Ther. 2019 Nov;26(11-12):347-355. doi: 10.1038/s41417-018-0070-x. Epub 2019 Jan 9.
14 ASPP2 suppresses invasion and TGF-1-induced epithelial-mesenchymal transition by inhibiting Smad7 degradation mediated by E3 ubiquitin ligase ITCH in gastric cancer.Cancer Lett. 2017 Jul 10;398:52-61. doi: 10.1016/j.canlet.2017.04.002. Epub 2017 Apr 9.
15 Notch signaling facilitates hepatitis B virus covalently closed circular DNA transcription via cAMP response element-binding protein with E3 ubiquitin ligase-modulation.Sci Rep. 2019 Feb 7;9(1):1621. doi: 10.1038/s41598-018-38139-5.
16 Parkin facilitates proteasome inhibitor-induced apoptosis via suppression of NF-B activity in hepatocellular carcinoma.Cell Death Dis. 2019 Sep 26;10(10):719. doi: 10.1038/s41419-019-1881-x.
17 Characterization of Elements Regulating the Nuclear-to-Cytoplasmic Translocation of ICP0 in Late Herpes Simplex Virus 1 Infection.J Virol. 2018 Jan 2;92(2):e01673-17. doi: 10.1128/JVI.01673-17. Print 2018 Jan 15.
18 Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder. Mol Psychiatry. 2019 Nov;24(11):1748-1768. doi: 10.1038/s41380-018-0065-x. Epub 2018 May 4.
19 Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182.Oncol Rep. 2016 Apr;35(4):2461-5. doi: 10.3892/or.2016.4605. Epub 2016 Feb 1.
20 DCUN1D1 facilitates tumor metastasis by activating FAK signaling and up-regulates PD-L1 in non-small-cell lung cancer.Exp Cell Res. 2019 Jan 15;374(2):304-314. doi: 10.1016/j.yexcr.2018.12.001. Epub 2018 Dec 4.
21 Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance.Mol Pharmacol. 2019 Nov;96(5):641-654. doi: 10.1124/mol.119.117069. Epub 2019 Sep 6.
22 Speckle-type POZ protein suppresses lipid accumulation and prostate cancer growth by stabilizing fatty acid synthase.Prostate. 2019 Jun;79(8):864-871. doi: 10.1002/pros.23793. Epub 2019 Apr 7.
23 Imprinting effects of UBE3A loss on synaptic gene networks and Wnt signaling pathways.Hum Mol Genet. 2019 Nov 15;28(22):3842-3852. doi: 10.1093/hmg/ddz221.
24 LncRNA DUXAP9-206 directly binds with Cbl-b to augment EGFR signaling and promotes non-small cell lung cancer progression.J Cell Mol Med. 2019 Mar;23(3):1852-1864. doi: 10.1111/jcmm.14085. Epub 2018 Dec 4.
25 Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1.Mol Med Rep. 2018 Dec;18(6):5701-5708. doi: 10.3892/mmr.2018.9576. Epub 2018 Oct 23.
26 The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer.Oncotarget. 2017 Mar 21;8(12):20288-20296. doi: 10.18632/oncotarget.15446.
27 Rhododendrin-Induced RNF146 Expression via Estrogen Receptor Activation is Cytoprotective Against 6-OHDA-Induced Oxidative Stress.Int J Mol Sci. 2019 Apr 10;20(7):1772. doi: 10.3390/ijms20071772.
28 The homeobox transcription factor MEIS2 is a regulator of cancer cell survival and IMiDs activity in Multiple Myeloma: modulation by Bromodomain and Extra-Terminal (BET) protein inhibitors.Cell Death Dis. 2019 Apr 11;10(4):324. doi: 10.1038/s41419-019-1562-9.
29 Parkin Overexpression Ameliorates PrP106-126-Induced Neurotoxicity via Enhanced Autophagy in N2a Cells.Cell Mol Neurobiol. 2017 May;37(4):717-728. doi: 10.1007/s10571-016-0407-7. Epub 2016 Jul 18.
30 Von Hippel-Lindau gene product directs cytokinesis: a new tumor suppressor function.J Cell Sci. 2011 Jul 1;124(Pt 13):2132-42. doi: 10.1242/jcs.087122. Epub 2011 Jun 7.
31 FBXW7 mutations reduce binding of NOTCH1, leading to cleaved NOTCH1 accumulation and target gene activation in CLL.Blood. 2019 Feb 21;133(8):830-839. doi: 10.1182/blood-2018-09-874529. Epub 2018 Dec 3.
32 Clarifying the function of genes at the chromosome 16p13 locus in type 1 diabetes: CLEC16A and DEXI.Genes Immun. 2020 Feb;21(2):79-82. doi: 10.1038/s41435-019-0087-7. Epub 2019 Oct 1.
33 ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653.Aging (Albany NY). 2019 Dec 10;11(23):11202-11223. doi: 10.18632/aging.102525. Epub 2019 Dec 10.
34 Cancer-causing mutations in a novel transcription-dependent nuclear export motif of VHL abrogate oxygen-dependent degradation of hypoxia-inducible factor.Mol Cell Biol. 2008 Jan;28(1):302-14. doi: 10.1128/MCB.01044-07. Epub 2007 Oct 29.
35 The landscape of Parkin variants reveals pathogenic mechanisms and therapeutic targets in Parkinson's disease.Hum Mol Genet. 2019 Sep 1;28(17):2811-2825. doi: 10.1093/hmg/ddz080.
36 Post-translational modification of Parkin and its research progress in cancer.Cancer Commun (Lond). 2019 Nov 21;39(1):77. doi: 10.1186/s40880-019-0421-5.
37 Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells.Cancer Sci. 2019 Apr;110(4):1268-1278. doi: 10.1111/cas.13953. Epub 2019 Feb 21.
38 HIF2-Targeted RNAi Therapeutic Inhibits Clear Cell Renal Cell Carcinoma.Mol Cancer Ther. 2018 Jan;17(1):140-149. doi: 10.1158/1535-7163.MCT-17-0471. Epub 2017 Oct 27.
39 Cul1 promotes melanoma cell proliferation by promoting DEPTOR degradation and enhancing cap-dependent translation.Oncol Rep. 2016 Feb;35(2):1049-56. doi: 10.3892/or.2015.4442. Epub 2015 Nov 23.
40 Upregulation of HRD1 promotes cell migration and invasion in colon cancer.Mol Cell Biochem. 2019 Apr;454(1-2):1-9. doi: 10.1007/s11010-018-3447-0. Epub 2018 Oct 10.
41 E3 ubiquitin ligase CHIP attenuates cellular proliferation and invasion abilities in triple-negative breast cancer cells.Clin Exp Med. 2020 Feb;20(1):109-119. doi: 10.1007/s10238-019-00594-3. Epub 2019 Dec 16.
42 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.