ubiquitin carboxyl-terminal hydrolase CYLD; deubiquitinating enzyme CYLD; ubiquitin thiolesterase CYLD; ubiquitin-specific-processing protease CYLD (CYLD, CYLD1, KIAA0849, HSPC057)

Function: - protease - specifically cleaves Lys-63-linked polyubiquitin chains - has endodeubiquitinase activity - role in regulation of pathways leading to NF-kappa-B activation - contributes to regulation of cell survival, proliferation & differentiation via its effects on NF-kappa-B activation - negative regulator of Wnt signaling - inhibits HDAC6 & thus promotes acetylation of alpha-tubulin & stabilization of microtubules - role in regulation of microtubule dynamics, & thus contributes to regulation of cell proliferation, cell polarization, cell migration, & angiogenesis - required for normal cell cycle progress & normal cytokinesis - inhibits nuclear translocation of NF-kappa-B - role in inflammation & the innate immune response, via its effects on NF-kappa-B activation - role in maturation of natural killer cells (NK cells) a) dispensable for maturation of intrathymic NK cells b) required for continued survival of immature NK cells - negatively regulates TNFRSF11A signaling & genesis of osteoclasts (putative) - thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin - inhibited by phosphorylation at Ser - phosphorylated on several Ser by IKKA &/or IKKB in response to immune stimuli - phosphorylation requires IKBKG - phosphorylation abolishes TRAF2 deubiquitination, interferes with activation of Jun kinases, & strongly reduces CD40-dependent gene activation by NF-kappa-B - interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-rich C-terminal region) - interacts with TRAF2 & TRIP - interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE & DDX58 - interacts (via CAP-Gly domain) with microtubules - interacts with HDAC6 & BCL3 - interacts with SQSTM1 & MAP3K7 - identified in a complex with TRAF6 & SQSTM1 (putative) Structure: - belongs to the peptidase C67 family - contains 3 CAP-Gly domains Compartment: - cytoplasm, perinuclear region, cytoskeleton - plasma membrane, cytoplasmic side - associates with microtubule cytoskeleton during interphase - associated with midbody during telophase Alternative splicing: named isoforms=2 Expression: - expressed in fetal brain, testis, & skeletal muscle - lower expression in adult brain, leukocytes, liver, heart, kidney, spleen, ovary & lung - isoform 2 is found in all tissues except kidney Pathology: - defects in CYLD are the cause of a) familial cylindromatosis b) multiple familial trichoepithelioma type 1 c) Brooke-Spiegler syndrome

Related

familial cylindromatosis; Ancell-Spiegler cylindromas; dermal eccrine cylindromatosis; turban tumor syndrome ubiquitin (UBCEP2, UBB, UBC)

General

metalloprotein oligomerizing protein phosphoprotein ubiquitin C-terminal hydrolase; UCH; ubiquitin thiolesterase; ubiquitin-specific processing protease; deubiquitinating enzyme

Properties

SIZE: entity length = 956 aa MW = 107 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: TRIP interaction {106-593} MOTIF: CAP/Gly domain {153-198} MOTIF: glycine residue (SEVERAL) CAP/Gly domain {253-286} MOTIF: glycine residue (SEVERAL) TRAF2 interaction {394-469} Ser phosphorylation site {S399} Ser phosphorylation site {S418} IKBKG/NEMO interaction {470-554} CAP/Gly domain {492-535} MOTIF: glycine residue (SEVERAL) cysteine residue {C601} Zn+2-binding site SITE: 788-788 Zn+2-binding site SITE: 791-791 Zn+2-binding site SITE: 799-799 Zn+2-binding site SITE: 802-802 Zn+2-binding site SITE: 817-817 Zn+2-binding site SITE: 820-820 Zn+2-binding site SITE: 825-825 Zn+2-binding site SITE: 833-833 histidine residue {H871}

Database Correlations

OMIM correlations MORBIDMAP 605018 UniProt Q9NQC7 PFAM correlations Entrez Gene 1540 Kegg hsa:1540 ENZYME 3.4.19.12

References

UniProt :accession Q9NQC7