m6A Regulator Information

General Information of the m6A Regulator (ID: REG00018)
Regulator Name Methyltransferase-like 5 (METTL5)
Synonyms
rRNA N6-adenosine-methyltransferase METTL5; DC3; HSPC133
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Gene Name METTL5
Sequence
MKKVRLKELESRLQQVDGFEKPKLLLEQYPTRPHIAACMLYTIHNTYDDIENKVVADLGC
GCGVLSIGTAMLGAGLCVGFDIDEDALEIFNRNAEEFELTNIDMVQCDVCLLSNRMSKSF
DTVIMNPPFGTKNNKGTDMAFLKTALEMARTAVYSLHKSSTREHVQKKAAEWKIKIDIIA
ELRYDLPASYKFHKKKSVDIEVDLIRFSF
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Family methyltransferase superfamily; PrmA family
Function
Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA. N6-methylation of adenine(1832) in 18S rRNA resides in the decoding center of 18S rRNA and is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation.
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Gene ID 29081
Uniprot ID
METL5_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
METTL5 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
Myc proto-oncogene protein (MYC)
 Target Gene 
Pancreatic cancer [ICD-11: 2C10]
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 Pancreatic cancer [ICD-11: 2C10]
Cell Process Cell proliferation
Cell migration
Cell invasion
Response Summary The study revealed important roles for METTL5 in the development of pancreatic cancer and present the METTL5/Myc proto-oncogene protein (MYC) axis as a novel therapeutic strategy for treatment.
DNA mismatch repair protein Msh2 (MSH2)
 Target Gene 
Endometrial cancer [ICD-11: 2C76]
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 Endometrial cancer [ICD-11: 2C76]
Target Regulation Up regulation
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model
 CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Response Summary Knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the DNA mismatch repair protein Msh2 (MSH2), MSH6 and PMS2 expression in MMR.
DNA mismatch repair protein Msh6 (MSH6)
 Target Gene 
Endometrial cancer [ICD-11: 2C76]
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 Endometrial cancer [ICD-11: 2C76]
Target Regulation Up regulation
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model
 CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Response Summary Knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, DNA mismatch repair protein Msh6 (MSH6) and PMS2 expression in MMR.
Mismatch repair endonuclease PMS2 (PMS2)
 Target Gene 
Endometrial cancer [ICD-11: 2C76]
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 Endometrial cancer [ICD-11: 2C76]
Target Regulation Up regulation
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model
 CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Response Summary Knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, MSH6 and Mismatch repair endonuclease PMS2 (PMS2) expression in MMR.
18S rRNA
 Target Gene 
Liver cancer [ICD-11: 2C12]
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 Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation Up regulation
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model A total of 1 × 106 HuCCT1-sgNC and HuCCT1-sgMETTL5 cells in 0.2 mL of PBS were separately injected into 6-week-old male NCG mice (N = 7 per group) via caudal vein. Mice were sacrificed at 4 weeks after injection, and the lung tissues were processed into 4-mm-thick paraffin-embedded sections. H&E staining was subsequently performed to determine the pulmonary metastasis.
Heat shock factor protein 4 (HSF4B)
 Target Gene 
Nasopharyngeal carcinoma [ICD-11: 2B6B]
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 Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation Up regulation
In-vitro Model
 C666-1 Nasopharyngeal carcinoma Homo sapiens CVCL_7949
HK1 Nasopharyngeal carcinoma Acipenser baerii CVCL_YE27
HONE-1 Nasopharyngeal carcinoma Homo sapiens CVCL_8706
S18 Nasopharyngeal carcinoma Homo sapiens CVCL_B0U9
S26 Nasopharyngeal carcinoma Homo sapiens CVCL_B0UB
5-8F Nasopharyngeal carcinoma Homo sapiens CVCL_C528
6-10B Nasopharyngeal carcinoma Homo sapiens CVCL_C529
HNE-1 Nasopharyngeal carcinoma Homo sapiens CVCL_0308
In-vivo Model Female BALB/c nude mice aged 5 weeks were used to perform in vivo proliferation and metastasis assays. For subcutaneous xenograft tumor model, 1×106 6-10B cells in 200 μL PBS were injected into the dorsal flank of each mouse (n = 7 in each group). The long and short diameters of subcutaneous tumors were measured every 3 days until the endpoint. Mice were sacrificed about 4 weeks after injection, and subcutaneous tumors were harvested, weighted and then fixed in 4% paraformaldehyde for subsequent analysis. For inguinal lymph node metastasis model, 1×105 5-8F cells in 30 μL of PBS were injected into the right foot pad of each mouse (n = 7 in each group). Mice were sacrificed about one month after injection. Primary foot pad tumor and metastatic inguinal lymph nodes were harvested and fixed in 4% paraformaldehyde for subsequent assays.
Unspecific Target Gene
Gastric cancer [ICD-11: 2B72]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [5]
Responsed Disease Gastric cancer [ICD-11: 2B72]
Pathway Response Nucleotide excision repair hsa03420), Oxidative phosphorylation
Cell Process Oxidative phosphorylation
Nucleotide excision repair
Mismatch repair
Response Summary METTL5 protein was decreased in GCTs compared with AIMTs and ANTs, and it is a potential prognostic biomarker in GC.
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [6]
Responsed Disease Breast cancer [ICD-11: 2C60]
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
ZR75-30 Breast cancer Homo sapiens CVCL_1661
Response Summary METTL5 expression is elevated in breast cancer patient samples and is required for growth of several breast cancer cell lines.
Intellectual disability [ICD-11: 6A00]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [7]
Responsed Disease Intellectual disability [ICD-11: 6A00]
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Mettl5 +/- mice with C57BL/6N background were generated by using CRISPR-Cas9 systems. The exon 2, exon 3 and exon 4 of Mettl5 were deleted in the knockout Mettl5 allele. Mice were genotyped for the targeted allele by PCR using tail DNA.
Response Summary Mettl5 knockout in mESCs leads to the abnormal craniofacial and nervous development. Moreover, using Mettl5 knockout mouse model, we further demonstrated that Mettl5 knockout mice exhibit intellectual disability, recapitulating the human phenotype.
Click to View Potential Drug Response of This Regulator
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Regulator
Non-coding RNA
m6A Target: 18S rRNA
 Target Gene 
In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05695
 Crosstalk Info 
Epigenetic Regulator 18S rRNA
Crosstalk relationship m6A → ncRNA
Disease Intrahepatic cholangiocarcinoma
 Disease Info 
References
Ref 1 Ribosome 18S m(6)A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c?Myc translation. Int J Oncol. 2022 Jan;60(1):9. doi: 10.3892/ijo.2021.5299. Epub 2021 Dec 31.
Ref 2 The potential role of methyltransferase-like 5 in deficient mismatch repair of uterine corpus endometrial carcinoma. Bioengineered. 2022 Mar;13(3):5525-5536. doi: 10.1080/21655979.2022.2036912.
Ref 3 Cyclic AMP inhibition of tumor necrosis factor alpha production induced by amyloidogenic C-terminal peptide of Alzheimer's amyloid precursor protein in macrophages: involvement of multiple intracellular pathways and cyclic AMP response element binding protein. Mol Pharmacol. 2003 Mar;63(3):690-8. doi: 10.1124/mol.63.3.690.
Ref 4 ClinicalTrials.gov (NCT04305795) An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 5 Expression and prognostic potential of ribosome 18S RNA m(6)A methyltransferase METTL5 in gastric cancer. Cancer Cell Int. 2021 Oct 26;21(1):569. doi: 10.1186/s12935-021-02274-3.
Ref 6 Ribosome 18S m(6)A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth. Cell Rep. 2020 Dec 22;33(12):108544. doi: 10.1016/j.celrep.2020.108544.
Ref 7 Mettl5 mediated 18S rRNA N6-methyladenosine (m(6)A) modification controls stem cell fate determination and neural function. Genes Dis. 2020 Jul 17;9(1):268-274. doi: 10.1016/j.gendis.2020.07.004. eCollection 2022 Jan.