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Overview

Uniprot IDQ96FW1
Protein NameUbiquitin thioesterase OTUB1
Gene NameOTUB1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
109 EALLDDSKELQRFKA
188 GYLQRESKFFEHFIE

Function

Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation (PubMed:12401499, PubMed:12704427, PubMed:14661020, PubMed:23827681). Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen (PubMed:14661020). Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy (PubMed:14661020). Isoform 1 destabilizes RNF128, leading to prevent anergy (PubMed:14661020). In contrast, isoform 2 stabilizes RNF128 and promotes anergy (PubMed:14661020). Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128 (PubMed:14661020). Deubiquitinates estrogen receptor alpha (ESR1) (PubMed:19383985). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains (PubMed:18954305, PubMed:19211026, PubMed:23827681). Not able to cleave di-ubiquitin (PubMed:18954305, PubMed:23827681). Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (PubMed:18954305, PubMed:23827681)

Protein Sequence

10 MAAEEPQQQK 20 QEPLGSDSEG 30 VNCLAYDEAI 40 MAQQDRIQQE 50 IAVQNPLVSE 60 RLELSVLYKE 70 YAEDDNIYQQ 80 KIKDLHKKYS 90 YIRKTRPDGN 100 CFYRAFGFSH 110 LEALLDDSKE 120 LQRFKAVSAK 130 SKEDLVSQGF 140 TEFTIEDFHN 150 TFMDLIEQVE 160 KQTSVADLLA 170 SFNDQSTSDY 180 LVVYLRLLTS 190 GYLQRESKFF 200 EHFIEGGRTV 210 KEFCQQEVEP 220 MCKESDHIHI 230 IALAQALSVS 240 IQVEYMDRGE 250 GGTTNPHIFP 260 EGSEPKVYLL 270 YRPGHYDILY K

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005654 nucleoplasm
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0019784 deNEDDylase activity
Molecular Function GO:0043130 ubiquitin binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0055105 ubiquitin-protein transferase inhibitor activity
Biological Process GO:0002250 adaptive immune response
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:2000780 negative regulation of double-strand break repair
Biological Process GO:1904263 positive regulation of TORC1 signaling
Biological Process GO:0016579 protein deubiquitination
Biological Process GO:0071108 protein K48-linked deubiquitination
Biological Process GO:0006508 proteolysis

Reference

[1] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[2] 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.