Search Results

Overview

Uniprot IDP57081
Protein NametRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
Gene NameWDR4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
373 DNVTSYLKKKEERLQ
374 NVTSYLKKKEERLQQ
385 RLQQQLEKKQRRRSP
386 LQQQLEKKQRRRSPP
402 GPDGHAKKMRPGEAT

Function

Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, PubMed:37369656). In the METTL1-WDR4 methyltransferase complex, WDR4 acts as a scaffold for tRNA-binding (PubMed:36599982, PubMed:36599985, PubMed:37369656). Required for the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352206, PubMed:34352207, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also required for the formation of N(7)-methylguanine at internal sites in a subset of mRNAs (PubMed:31031084, PubMed:37379838). Also required for methylation of a specific subset of miRNAs, such as let-7 (PubMed:31031083). Independently of METTL1, also plays a role in genome stability: localizes at the DNA replication site and regulates endonucleolytic activities of FEN1 (PubMed:26751069)

Protein Sequence

10 MAGSVGLALC 20 GQTLVVRGGS 30 RFLATSIASS 40 DDDSLFIYDC 50 SAAEKKSQEN 60 KGEDAPLDQG 70 SGAILASTFS 80 KSGSYFALTD 90 DSKRLILFRT 100 KPWQCLSVRT 110 VARRCTALTF 120 IASEEKVLVA 130 DKSGDVYSFS 140 VLEPHGCGRL 150 ELGHLSMLLD 160 VAVSPDDRFI 170 LTADRDEKIR 180 VSWAAAPHSI 190 ESFCLGHTEF 200 VSRISVVPTQ 210 PGLLLSSSGD 220 GTLRLWEYRS 230 GRQLHCCHLA 240 SLQELVDPQA 250 PQKFAASRIA 260 FWCQENCVAL 270 LCDGTPVVYI 280 FQLDARRQQL 290 VYRQQLAFQH 300 QVWDVAFEET 310 QGLWVLQDCQ 320 EAPLVLYRPV 330 GDQWQSVPES 340 TVLKKVSGVL 350 RGNWAMLEGS 360 AGADASFSSL 370 YKATFDNVTS 380 YLKKKEERLQ 390 QQLEKKQRRR 400 SPPPGPDGHA 410 KKMRPGEATL SC

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0106143 tRNA (m7G46) methyltransferase complex
Cellular Component GO:0043527 tRNA methyltransferase complex
Molecular Function GO:0008047 enzyme activator activity
Biological Process GO:0006974 DNA damage response
Biological Process GO:0106004 tRNA (guanine-N7)-methylation
Biological Process GO:0006400 tRNA modification

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] 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] 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.