Search Results

Overview

Uniprot IDQ9HCE5
Protein NameN(6)-adenosine-methyltransferase non-catalytic subunit METTL14
Gene NameMETTL14
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
63 DTSAPNAKRKYLDEG
65 SAPNAKRKYLDEGET

Function

The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis (PubMed:24316715, PubMed:24407421, PubMed:25719671, PubMed:27281194, PubMed:27373337, PubMed:29348140). In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core (PubMed:27281194, PubMed:27373337, PubMed:27627798, PubMed:29348140). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing (PubMed:24316715, PubMed:24407421, PubMed:25719671). M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (By similarity). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity)

Protein Sequence

10 MDSRLQEIRE 20 RQKLRRQLLA 30 QQLGAESADS 40 IGAVLNSKDE 50 QREIAETRET 60 CRASYDTSAP 70 NAKRKYLDEG 80 ETDEDKMEEY 90 KDELEMQQDE 100 ENLPYEEEIY 110 KDSSTFLKGT 120 QSLNPHNDYC 130 QHFVDTGHRP 140 QNFIRDVGLA 150 DRFEEYPKLR 160 ELIRLKDELI 170 AKSNTPPMYL 180 QADIEAFDIR 190 ELTPKFDVIL 200 LEPPLEEYYR 210 ETGITANEKC 220 WTWDDIMKLE 230 IDEIAAPRSF 240 IFLWCGSGEG 250 LDLGRVCLRK 260 WGYRRCEDIC 270 WIKTNKNNPG 280 KTKTLDPKAV 290 FQRTKEHCLM 300 GIKGTVKRST 310 DGDFIHANVD 320 IDLIITEEPE 330 IGNIEKPVEI 340 FHIIEHFCLG 350 RRRLHLFGRD 360 STIRPGWLTV 370 GPTLTNSNYN 380 AETYASYFSA 390 PNSYLTGCTE 400 EIERLRPKSP 410 PPKSKSDRGG 420 GAPRGGGRGG 430 TSAGRGRERN 440 RSNFRGERGG 450 FRGGRGGAHR GGFPPR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0036396 RNA N6-methyladenosine methyltransferase complex
Molecular Function GO:0003729 mRNA binding
Molecular Function GO:0001734 mRNA m(6)A methyltransferase activity
Biological Process GO:0006974 DNA damage response
Biological Process GO:0021861 forebrain radial glial cell differentiation
Biological Process GO:0042063 gliogenesis
Biological Process GO:0061157 mRNA destabilization
Biological Process GO:0016556 mRNA modification
Biological Process GO:0006397 mRNA processing
Biological Process GO:0000398 mRNA splicing, via spliceosome
Biological Process GO:0048255 mRNA stabilization
Biological Process GO:1901533 negative regulation of hematopoietic progenitor cell differentiation
Biological Process GO:0045727 positive regulation of translation
Biological Process GO:0031053 primary miRNA processing
Biological Process GO:0045664 regulation of neuron differentiation
Biological Process GO:0045580 regulation of T cell differentiation
Biological Process GO:0031667 response to nutrient levels
Biological Process GO:0001510 RNA methylation
Biological Process GO:0007283 spermatogenesis
Biological Process GO:0019827 stem cell population maintenance

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[3] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.