m6A Regulator Information

General Information of the m6A Regulator (ID: REG00032)
Regulator Name E3 ubiquitin-protein ligase Hakai (CBLL1)
Synonyms
CBLL1; HAKAI; RNF188; EC 2.3.2.27; Casitas B-lineage lymphoma-transforming sequence-like protein 1; c-Cbl-like protein 1; RING finger protein 188; RING-type E3 ubiquitin transferase Hakai
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Gene Name CBLL1
Sequence
MDHTDNELQGTNSSGSLGGLDVRRRIPIKLISKQANKAKPAPRTQRTINRMPAKAPPGDE
EGFDYNEEERYDCKGGELFANQRRFPGHLFWDFQINILGEKDDTPVHFCDKCGLPIKIYG
RMIPCKHVFCYDCAILHEKKGDKMCPGCSDPVQRIEQCTRGSLFMCSIVQGCKRTYLSQR
DLQAHINHRHMRAGKPVTRASLENVHPPIAPPPTEIPERFIMPPDKHHMSHIPPKQHIMM
PPPPLQHVPHEHYNQPHEDIRAPPAELSMAPPPPRSVSQETFRISTRKHSNLITVPIQDD
SNSGAREPPPPAPAPAHHHPEYQGQPVVSHPHHIMPPQQHYAPPPPPPPPISHPMPHPPQ
AAGTPHLVYSQAPPPPMTSAPPPITPPPGHIIAQMPPYMNHPPPGPPPPQHGGPPVTAPP
PHHYNPNSLPQFTEDQGTLSPPFTQPGGMSPGIWPAPRGPPPPPRLQGPPSQTPLPGPHH
PDQTRYRPYYQ
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Family Hakai family
Function
E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (By similarity). Targets CDH1 for endocytosis and degradation (By similarity). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Its function in the WMM complex is unknown.
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Gene ID 79872
Uniprot ID
HAKAI_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Target Genes Click to View Potential Target Genes of This Regulator
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
CBLL1 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
72 kDa type IV collagenase (MMP2)
 Target Gene 
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
In-vitro Model
 A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
SK-MES-1 Lung squamous cell carcinoma Homo sapiens CVCL_0630
Response Summary CBLL1 was frequently upregulated in non-small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. CBLL1 knockdown inhibited cell invasion via increased E-cadherin protein expression, and decreased expression of 72 kDa type IV collagenase (MMP2) and MMP9 in NSCLC cell lines.
Kinesin-like protein KIF26B (KIF26B)
 Target Gene 
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In-vitro Model
 SK-LMS-1 Vulvar leiomyosarcoma Homo sapiens CVCL_0628
MDA-MB-157 Breast carcinoma Homo sapiens CVCL_0618
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
In-vivo Model BALB/c nude mice (5 weeks old) were purchased from the Beijing HFK Bioscience Co. Ltd. 2×106 cells (50 uL) were mixed with 50 uL Matrigel (BD Biosciences, San Jose, CA, USA) were injected subcutaneously in the rear flank fat pad of the nude mice (N = 6, per group).
Response Summary Ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.
Matrix metalloproteinase-9 (MMP9)
 Target Gene 
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
In-vitro Model
 A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
SK-MES-1 Lung squamous cell carcinoma Homo sapiens CVCL_0630
Response Summary CBLL1 was frequently upregulated in non-small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. CBLL1 knockdown inhibited cell invasion via increased E-cadherin protein expression, and decreased expression of MMP2 and Matrix metalloproteinase-9 (MMP9) in NSCLC cell lines.
Unspecific Target Gene
West nile virus infection [ICD-11: 1D46]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [3]
Responsed Disease West nile virus infection [ICD-11: 1D46]
In-vitro Model
 HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response Summary CBLL1 acts in concert with the ubiquitin proteasome system to mediate West Nile virus (WNV) infection internalization.
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In-vitro Model
 MDA-MB-157 Breast carcinoma Homo sapiens CVCL_0618
MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
SK-LMS-1 Vulvar leiomyosarcoma Homo sapiens CVCL_0628
In-vivo Model BALB/c nude mice (5 weeks old) were purchased from the Beijing HFK Bioscience Co. Ltd. 2×106 cells (50 uL) were mixed with 50 uL Matrigel (BD Biosciences, San Jose, CA, USA) were injected subcutaneously in the rear flank fat pad of the nude mice (N = 6, per group).
Response Summary KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.
Prostate cancer [ICD-11: 2C82]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [4]
Responsed Disease Prostate cancer [ICD-11: 2C82]
Cell Process Cell migration
Cell invasion
In-vitro Model
 PC-3 Prostate carcinoma Homo sapiens CVCL_0035
DU145 Prostate carcinoma Homo sapiens CVCL_0105
Response Summary Knockdown of HNRNPA2B1 or FTO prominently inhibited prostate cancer cells migration and invasion in vitro experiment. Determined CBLL1, FTO, YTHDC1, HNRNPA2B1 as crucial m6A regulators of prostate cancer.
Click to View Potential Drug Response of This Regulator
Xenobiotics Compound(s) Regulating the m6A Methylation Regulator
Compound Name Lipopolysaccharide Investigative
Synonyms
PMID23160791-compound-LPS
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Description
CBLL1 was significantly up-regulated in the rat cerebral cortex after LPS administration, which suggested CBLL1 might participate in regulating neuronal biological function after neuroinflammation.
 [5]
References
Ref 1 CBLL1 is highly expressed in non-small cell lung cancer and promotes cell proliferation and invasion. Thorac Cancer. 2019 Jun;10(6):1479-1488. doi: 10.1111/1759-7714.13097. Epub 2019 May 23.
Ref 2 Ginsenoside Rh2 reduces m6A RNA methylation in cancer via the KIF26B-SRF positive feedback loop. J Ginseng Res. 2021 Nov;45(6):734-743. doi: 10.1016/j.jgr.2021.05.004. Epub 2021 May 25.
Ref 3 Appraising the roles of CBLL1 and the ubiquitin/proteasome system for flavivirus entry and replication. J Virol. 2011 Mar;85(6):2980-9. doi: 10.1128/JVI.02483-10. Epub 2010 Dec 29.
Ref 4 RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer. Front Genet. 2021 Nov 26;12:768041. doi: 10.3389/fgene.2021.768041. eCollection 2021.
Ref 5 Upregulation of CBLL1 in rat brain cortex after lipopolysaccharide treated. J Mol Histol. 2013 Apr;44(2):135-45. doi: 10.1007/s10735-012-9467-2. Epub 2012 Nov 17.