Search Results

Overview

Uniprot IDQ96MU7
Protein NameYTH domain-containing protein 1
Gene NameYTHDC1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
127 SASREPYKNQPEKTC
132 PYKNQPEKTCVRKRD
565 HQRPGYLKDPRYQEV
82 SSSVSNNKRIVSTKG
96 GKSATEYKNEEYQRS

Function

Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). Independently of its N6-methyladenosine-containing RNA reader activity, it regulates PPARG stability by preventing its interaction with the E3 ubiquitin ligase ARIH2, thereby protecting it from ubiquitin-mediated proteasomal degradation and contributing to brown adipose tissue (BAT) development and energy homeostasis (By similarity)

Protein Sequence

10 MAADSREEKD 20 GELNVLDDIL 30 TEVPEQDDEL 40 YNPESEQDKN 50 EKKGSKRKSD 60 RMESTDTKRQ 70 KPSVHSRQLV 80 SKPLSSSVSN 90 NKRIVSTKGK 100 SATEYKNEEY 110 QRSERNKRLD 120 ADRKIRLSSS 130 ASREPYKNQP 140 EKTCVRKRDP 150 ERRAKSPTPD 160 GSERIGLEVD 170 RRASRSSQSS 180 KEEVNSEEYG 190 SDHETGSSGS 200 SDEQGNNTEN 210 EEEGVEEDVE 220 EDEEVEEDAE 230 EDEEVDEDGE 240 EEEEEEEEEE 250 EEEEEEEEEY 260 EQDERDQKEE 270 GNDYDTRSEA 280 SDSGSESVSF 290 TDGSVRSGSG 300 TDGSDEKKKE 310 RKRARGISPI 320 VFDRSGSSAS 330 ESYAGSEKKH 340 EKLSSSVRAV 350 RKDQTSKLKY 360 VLQDARFFLI 370 KSNNHENVSL 380 AKAKGVWSTL 390 PVNEKKLNLA 400 FRSARSVILI 410 FSVRESGKFQ 420 GFARLSSESH 430 HGGSPIHWVL 440 PAGMSAKMLG 450 GVFKIDWICR 460 RELPFTKSAH 470 LTNPWNEHKP 480 VKIGRDGQEI 490 ELECGTQLCL 500 LFPPDESIDL 510 YQVIHKMRHK 520 RRMHSQPRSR 530 GRPSRREPVR 540 DVGRRRPEDY 550 DIHNSRKKPR 560 IDYPPEFHQR 570 PGYLKDPRYQ 580 EVDRRFSGVR 590 RDVFLNGSYN 600 DYVREFHNMG 610 PPPPWQGMPP 620 YPGMEQPPHH 630 PYYQHHAPPP 640 QAHPPYSGHH 650 PVPHEARYRD 660 KRVHDYDMRV 670 DDFLRRTQAV 680 VSGRRSRPRE 690 RDRERERDRP 700 RDNRRDRERD 710 RGRDRERERE 720 RLCDRDRDRG ERGRYRR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016607 nuclear speck
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0140313 molecular sequestering activity
Molecular Function GO:0003729 mRNA binding
Molecular Function GO:1990247 N6-methyladenosine-containing RNA reader activity
Molecular Function GO:0003723 RNA binding
Biological Process GO:0050873 brown fat cell differentiation
Biological Process GO:0009048 dosage compensation by inactivation of X chromosome
Biological Process GO:0006406 mRNA export from nucleus
Biological Process GO:0006376 mRNA splice site recognition
Biological Process GO:0000398 mRNA splicing, via spliceosome
Biological Process GO:0010608 post-transcriptional regulation of gene expression
Biological Process GO:0000381 regulation of alternative mRNA splicing, via spliceosome
Biological Process GO:0048024 regulation of mRNA splicing, via spliceosome

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] 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.

[3] 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.

[4] 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.

[5] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[6] 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.

[7] 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.

[8] Chao L, Xu Y, Yang Y, Ao X, Liang J. Identification of lactylation-related biomarkers for diagnosis, prognosis, and treatment responsiveness in triple-negative breast cancer.. World J Surg Oncol 24(1):77. 2026 Jan 22. PMID: 41566505.

[9] 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.