Recombinant Mouse Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld), partial

Function

Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-induced necroptosis (PubMed:17548520, PubMed:28701375, PubMed:29291351, PubMed:32185393, PubMed:32424362). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:16713561). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (PubMed:16713561). Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules (PubMed:19893491). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (PubMed:16713561, PubMed:19893491, PubMed:20194890). Required for normal cell cycle progress and normal cytokinesis (PubMed:19893491). Inhibits nuclear translocation of NF-kappa-B (By similarity). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (By similarity). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (PubMed:16501569, PubMed:18643924). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (PubMed:18382763). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (PubMed:25134987). Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins (PubMed:28701375). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (By similarity). Involved in TNF-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (PubMed:28701375). Negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chain of NLRP6, thereby reducing the interaction between NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome (PubMed:32424362). Does not catalyze deubiquitination of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains (By similarity). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:17548520, PubMed:29291351). Also removes 'Lys-63'-linked polyubiquitin chains of MAP3K1 and MA3P3K3, which inhibit their interaction with MAP2K1 and MAP2K2 (By similarity)

Subcellular Location

Cytoplasm; Cytoplasm, perinuclear region; Cytoplasm, cytoskeleton; Cell membrane (Peripheral membrane protein); Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle; Cytoplasm, cytoskeleton, cilium basal body

Subunit

Interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-rich C-terminal region) (By similarity). Interacts with TRAF2 and TRIP (By similarity). Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and RIGI (By similarity). Interacts (via CAP-Gly domain) with microtubules (PubMed:19893491). Interacts with HDAC6 and BCL3 (PubMed:16713561, PubMed:19893491). Interacts with MAP3K7 (PubMed:17548520). Identified in a complex with TRAF6 and SQSTM1 (PubMed:18382763). Interacts with OPTN and SQSTM1 (By similarity). Interacts with CEP350 (By similarity). Interacts with RNF31; the interaction is indirect and is mediated via SPATA2 (By similarity). Interacts with SPATA2 (via the PUB domain); the interaction is direct and recruits CYLD to the LUBAC complex, thereby regulating TNF-induced necroptosis (By similarity)

• Okazaki N. et al. Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. — DNA Res. (2003)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Church D.M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. — PLoS Biol. (2009)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Massoumi R. et al. Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling. — Cell (2006)
• Reiley W.W. et al. Regulation of T cell development by the deubiquitinating enzyme CYLD. — Nat. Immunol. (2006)
• Reiley W.W. et al. Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses. — J. Exp. Med. (2007)
• Lim J.H. et al. CYLD is a crucial negative regulator of innate immune response in Escherichia coli pneumonia. — Cell. Microbiol. (2008)