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
    Click to Show/Hide
Gene Name METTL5
Sequence
MKKVRLKELESRLQQVDGFEKPKLLLEQYPTRPHIAACMLYTIHNTYDDIENKVVADLGC
GCGVLSIGTAMLGAGLCVGFDIDEDALEIFNRNAEEFELTNIDMVQCDVCLLSNRMSKSF
DTVIMNPPFGTKNNKGTDMAFLKTALEMARTAVYSLHKSSTREHVQKKAAEWKIKIDIIA
ELRYDLPASYKFHKKKSVDIEVDLIRFSF
    Click to Show/Hide
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.
    Click to Show/Hide
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 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL5
Cell Line Mouse liver cells Mus musculus
Treatment: METTL5 knockout liver cells
Control: WT liver cells
 GSE174418
Regulation
logFC: 2.11E+00
p-value: 1.69E-05
More Results Click to View More RNA-seq Results
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.
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 [3]
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 [4]
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 [5]
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
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 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 4 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 5 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.