Protease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Has endodeubiquitinase activity. Plays an important role in the regulation of pathways leading to NF-kappa-B activation. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation. Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules. Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis. Required for normal cell cycle progress and normal cytokinesis. Inhibits nuclear translocation of NF-kappa-B. Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation. Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells. Negatively regulates TNFRSF11A signaling and osteoclastogenesis. Interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-rich C-terminal region). Interacts with TRAF2 and TRIP. Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and DDX58. Interacts (via CAP-Gly domain) with microtubules. Interacts with HDAC6 and BCL3. Interacts with SQSTM1 and MAP3K7. Identified in a complex with TRAF6 and SQSTM1. Detected in fetal brain, testis, and skeletal muscle, and at a lower level in adult brain, leukocytes, liver, heart, kidney, spleen, ovary and lung. Isoform 2 is found in all tissues except kidney. Inhibited by phosphorylation at serine residues. Belongs to the peptidase C67 family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Cellular Component: extrinsic to internal side of plasma membrane; cytoplasmic microtubule; perinuclear region of cytoplasm; midbody; cytosol
Molecular Function: ubiquitin thiolesterase activity; protein binding; zinc ion binding; ubiquitin-specific protease activity; protein kinase binding
Biological Process: ubiquitin-dependent protein catabolic process; Wnt receptor signaling pathway; inhibition of NF-kappaB transcription factor; regulation of mitotic cell cycle; innate immune response; negative regulation of NF-kappaB import into nucleus; cell cycle; negative regulation of interferon type I production
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.