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Overview

Uniprot IDQ86UK7
Protein NameE3 ubiquitin-protein ligase ZNF598
Gene NameZNF598
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
850 TKSKKNKKSAWQATT

Function

E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:32099016, PubMed:32579943, PubMed:33581075). ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs (PubMed:28065601, PubMed:28132843, PubMed:28685749). Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:30293783). Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10 (PubMed:28065601, PubMed:28132843, PubMed:28685749). Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides (PubMed:32099016, PubMed:32579943, PubMed:36302773). E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3 (PubMed:28685749). Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs (PubMed:22751931, PubMed:32726578). Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression (PubMed:29719242)

Protein Sequence

10 MAAAGGAEGR 20 RAALEAAAAA 30 APERGGGSCV 40 LCCGDLEATA 50 LGRCDHPVCY 60 RCSTKMRVLC 70 EQRYCAVCRE 80 ELRQVVFGKK 90 LPAFATIPIH 100 QLQHEKKYDI 110 YFADGKVYAL 120 YRQLLQHECP 130 RCPELPPFSL 140 FGDLEQHMRR 150 QHELFCCRLC 160 LQHLQIFTYE 170 RKWYSRKDLA 180 RHRMQGDPDD 190 TSHRGHPLCK 200 FCDERYLDND 210 ELLKHLRRDH 220 YFCHFCDSDG 230 AQDYYSDYAY 240 LREHFREKHF 250 LCEEGRCSTE 260 QFTHAFRTEI 270 DLKAHRTACH 280 SRSRAEARQN 290 RHIDLQFSYA 300 PRHSRRNEGV 310 VGGEDYEEVD 320 RYSRQGRVAR 330 AGTRGAQQSR 340 RGSWRYKREE 350 EDREVAAAVR 360 ASVAAQQQEE 370 ARRSEDQEEG 380 GRPKKEEAAA 390 RGPEDPRGPR 400 RSPRTQGEGP 410 GPKETSTNGP 420 VSQEAFSVTG 430 PAAPGCVGVP 440 GALPPPSPKL 450 KDEDFPSLSA 460 STSSSCSTAA 470 TPGPVGLALP 480 YAIPARGRSA 490 FQEEDFPALV 500 SSVPKPGTAP 510 TSLVSAWNSS 520 SSSKKVAQPP 530 LSAQATGSGQ 540 PTRKAGKGSR 550 GGRKGGPPFT 560 QEEEEDGGPA 570 LQELLSTRPT 580 GSVSSTLGLA 590 SIQPSKVGKK 600 KKVGSEKPGT 610 TLPQPPPATC 620 PPGALQAPEA 630 PASRAEGPVA 640 VVVNGHTEGP 650 APARSAPKEP 660 PGLPRPLGSF 670 PCPTPQEDFP 680 ALGGPCPPRM 690 PPPPGFSAVV 700 LLKGTPPPPP 710 PGLVPPISKP 720 PPGFSGLLPS 730 PHPACVPSPA 740 TTTTTKAPRL 750 LPAPRAYLVP 760 ENFRERNLQL 770 IQSIRDFLQS 780 DEARFSEFKS 790 HSGEFRQGLI 800 SAAQYYKSCR 810 DLLGENFQKV 820 FNELLVLLPD 830 TAKQQELLSA 840 HTDFCNREKP 850 LSTKSKKNKK 860 SAWQATTQQA 870 GLDCRVCPTC 880 QQVLAHGDAS 890 SHQALHAARD 900 DDFPSLQAIA RIIT

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Cellular Component GO:0022626 cytosolic ribosome
Molecular Function GO:0140517 protein-RNA adaptor activity
Molecular Function GO:0043022 ribosome binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0170011 stalled ribosome sensor activity
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0004842 ubiquitin-protein transferase activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0045947 negative regulation of translational initiation
Biological Process GO:1990261 pre-mRNA catabolic process
Biological Process GO:0070534 protein K63-linked ubiquitination
Biological Process GO:0006513 protein monoubiquitination
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0072344 rescue of stalled cytosolic ribosome
Biological Process GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process

Reference

[1] 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.

[2] 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.