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Overview

Uniprot IDQ01804
Protein NameOTU domain-containing protein 4
Gene NameOTUD4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1040 ILRSGRSKQFYNQTY
330 KHTSKNLKAPPPESW

Function

Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111)

Protein Sequence

10 MEAAVGVPDG 20 GDQGGAGPRE 30 DATPMDAYLR 40 KLGLYRKLVA 50 KDGSCLFRAV 60 AEQVLHSQSR 70 HVEVRMACIH 80 YLRENREKFE 90 AFIEGSFEEY 100 LKRLENPQEW 110 VGQVEISALS 120 LMYRKDFIIY 130 REPNVSPSQV 140 TENNFPEKVL 150 LCFSNGNHYD 160 IVYPIKYKES 170 SAMCQSLLYE 180 LLYEKVFKTD 190 VSKIVMELDT 200 LEVADEDNSE 210 ISDSEDDSCK 220 SKTAAAAADV 230 NGFKPLSGNE 240 QLKNNGNSTS 250 LPLSRKVLKS 260 LNPAVYRNVE 270 YEIWLKSKQA 280 QQKRDYSIAA 290 GLQYEVGDKC 300 QVRLDHNGKF 310 LNADVQGIHS 320 ENGPVLVEEL 330 GKKHTSKNLK 340 APPPESWNTV 350 SGKKMKKPST 360 SGQNFHSDVD 370 YRGPKNPSKP 380 IKAPSALPPR 390 LQHPSGVRQH 400 AFSSHSSGSQ 410 SQKFSSEHKN 420 LSRTPSQIIR 430 KPDRERVEDF 440 DHTSRESNYF 450 GLSPEERREK 460 QAIEESRLLY 470 EIQNRDEQAF 480 PALSSSSVNQ 490 SASQSSNPCV 500 QRKSSHVGDR 510 KGSRRRMDTE 520 ERKDKDSIHG 530 HSQLDKRPEP 540 STLENITDDK 550 YATVSSPSKS 560 KKLECPSPAE 570 QKPAEHVSLS 580 NPAPLLVSPE 590 VHLTPAVPSL 600 PATVPAWPSE 610 PTTFGPTGVP 620 APIPVLSVTQ 630 TLTTGPDSAV 640 SQAHLTPSPV 650 PVSIQAVNQP 660 LMPLPQTLSL 670 YQDPLYPGFP 680 CNEKGDRAIV 690 PPYSLCQTGE 700 DLPKDKNILR 710 FFFNLGVKAY 720 SCPMWAPHSY 730 LYPLHQAYLA 740 ACRMYPKVPV 750 PVYPHNPWFQ 760 EAPAAQNESD 770 CTCTDAHFPM 780 QTEASVNGQM 790 PQPEIGPPTF 800 SSPLVIPPSQ 810 VSESHGQLSY 820 QADLESETPG 830 QLLHADYEES 840 LSGKNMFPQP 850 SFGPNPFLGP 860 VPIAPPFFPH 870 VWYGYPFQGF 880 IENPVMRQNI 890 VLPSDEKGEL 900 DLSLENLDLS 910 KDCGSVSTVD 920 EFPEARGEHV 930 HSLPEASVSS 940 KPDEGRTEQS 950 SQTRKADTAL 960 ASIPPVAEGK 970 AHPPTQILNR 980 ERETVPVELE 990 PKRTIQSLKE 1000 KTEKVKDPKT 1010 AADVVSPGAN 1020 SVDSRVQRPK 1030 EESSEDENEV 1040 SNILRSGRSK 1050 QFYNQTYGSR 1060 KYKSDWGYSG 1070 RGGYQHVRSE 1080 ESWKGQPSRS 1090 RDEGYQYHRN 1100 VRGRPFRGDR 1110 RRSGMGDGHR GQHT

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005634 nucleus
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0061578 K63-linked deubiquitinase activity
Molecular Function GO:0060090 molecular adaptor activity
Molecular Function GO:0003723 RNA binding
Biological Process GO:0140374 antiviral innate immune response
Biological Process GO:0006307 DNA alkylation repair
Biological Process GO:2000660 negative regulation of interleukin-1-mediated signaling pathway
Biological Process GO:0034122 negative regulation of toll-like receptor signaling pathway
Biological Process GO:0035871 protein K11-linked deubiquitination
Biological Process GO:0071108 protein K48-linked deubiquitination
Biological Process GO:0070536 protein K63-linked deubiquitination
Biological Process GO:0006508 proteolysis
Biological Process GO:1903093 regulation of protein K48-linked deubiquitination

Reference

[1] 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.