CYLD: 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.
Protein type: Ubiquitin conjugating system; Ubiquitin-specific protease; EC 3.4.19.12; Protease; Tumor suppressor
Cellular Component: cell projection; centrosome; cytoplasm; cytoplasmic microtubule; cytoskeleton; cytosol; extrinsic to internal side of plasma membrane; membrane; microtubule; midbody; plasma membrane; spindle
Molecular Function: cysteine-type peptidase activity; hydrolase activity; metal ion binding; peptidase activity; protein binding; protein kinase binding; ubiquitin-specific protease activity; zinc ion binding
Biological Process: inhibition of NF-kappaB transcription factor; negative regulation of NF-kappaB import into nucleus; negative regulation of T cell differentiation; protein deubiquitination; proteolysis; regulation of mitotic cell cycle; ubiquitin-dependent protein catabolic process; Wnt receptor signaling pathway
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