Search Results

Overview

Uniprot IDQ08J23
Protein NameRNA cytosine C(5)-methyltransferase NSUN2
Gene NameNSUN2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
257 QIDVDGRKEILFYDR
28 DGAEGGGKRGEAGWE
437 KSSMPWNKRQPKLQG
441 PWNKRQPKLQGKSAE
445 RQPKLQGKSAETRES
498 LENNGSKKDGVCGPP
508 VCGPPPSKKMKLFGF
509 CGPPPSKKMKLFGFK
511 PPPSKKMKLFGFKED
586 KVINTGIKVWCRNNS
640 QENPFFRKLSSETYS

Function

RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847)

Protein Sequence

10 MGRRSRGRRL 20 QQQQRPEDAE 30 DGAEGGGKRG 40 EAGWEGGYPE 50 IVKENKLFEH 60 YYQELKIVPE 70 GEWGQFMDAL 80 REPLPATLRI 90 TGYKSHAKEI 100 LHCLKNKYFK 110 ELEDLEVDGQ 120 KVEVPQPLSW 130 YPEELAWHTN 140 LSRKILRKSP 150 HLEKFHQFLV 160 SETESGNISR 170 QEAVSMIPPL 180 LLNVRPHHKI 190 LDMCAAPGSK 200 TTQLIEMLHA 210 DMNVPFPEGF 220 VIANDVDNKR 230 CYLLVHQAKR 240 LSSPCIMVVN 250 HDASSIPRLQ 260 IDVDGRKEIL 270 FYDRILCDVP 280 CSGDGTMRKN 290 IDVWKKWTTL 300 NSLQLHGLQL 310 RIATRGAEQL 320 AEGGRMVYST 330 CSLNPIEDEA 340 VIASLLEKSE 350 GALELADVSN 360 ELPGLKWMPG 370 ITQWKVMTKD 380 GQWFTDWDAV 390 PHSRHTQIRP 400 TMFPPKDPEK 410 LQAMHLERCL 420 RILPHHQNTG 430 GFFVAVLVKK 440 SSMPWNKRQP 450 KLQGKSAETR 460 ESTQLSPADL 470 TEGKPTDPSK 480 LESPSFTGTG 490 DTEIAHATED 500 LENNGSKKDG 510 VCGPPPSKKM 520 KLFGFKEDPF 530 VFIPEDDPLF 540 PPIEKFYALD 550 PSFPRMNLLT 560 RTTEGKKRQL 570 YMVSKELRNV 580 LLNNSEKMKV 590 INTGIKVWCR 600 NNSGEEFDCA 610 FRLAQEGIYT 620 LYPFINSRII 630 TVSMEDVKIL 640 LTQENPFFRK 650 LSSETYSQAK 660 DLAKGSIVLK 670 YEPDSANPDA 680 LQCPIVLCGW 690 RGKASIRTFV 700 PKNERLHYLR 710 MMGLEVLGEK 720 KKEGVILTNE 730 SAASTGQPDN 740 DVTEGQRAGE 750 PNSPDAEEAN 760 SPDVTAGCDP AGVHPPR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0033391 chromatoid body
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005819 spindle
Molecular Function GO:0062152 mRNA (cytidine-5-)-methyltransferase activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0016428 tRNA (cytidine-5-)-methyltransferase activity
Molecular Function GO:0000049 tRNA binding
Biological Process GO:0051301 cell division
Biological Process GO:0048820 hair follicle maturation
Biological Process GO:0033313 meiotic cell cycle checkpoint signaling
Biological Process GO:0006397 mRNA processing
Biological Process GO:0010793 regulation of mRNA export from nucleus
Biological Process GO:2000736 regulation of stem cell differentiation
Biological Process GO:0007286 spermatid development
Biological Process GO:0030488 tRNA methylation
Biological Process GO:0006400 tRNA modification
Biological Process GO:0036416 tRNA stabilization

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] 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.

[4] 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.

[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.