CYLD Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis. 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. 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. Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-alpha-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins. Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation. Involved in TNF-alpha-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1. Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades. Belongs to the peptidase C19 family. 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. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Protease; Tumor suppressor; Ubiquitin conjugating system; Ubiquitin-specific protease
Chromosomal Location of human Ortholog: 16q12.1
Cellular Component:  centrosome; ciliary basal body; ciliary tip; cytoplasmic microtubule; cytosol; extrinsic component of cytoplasmic side of plasma membrane; midbody; perinuclear region of cytoplasm; spindle
Molecular Function:  cysteine-type deubiquitinase activity; Lys63-specific deubiquitinase activity; proline-rich region binding; protein binding; protein kinase binding; zinc ion binding
Biological Process:  cell cycle; innate immune response; necroptotic process; negative regulation of canonical Wnt signaling pathway; negative regulation of inflammatory response; negative regulation of interleukin-18-mediated signaling pathway; negative regulation of JNK cascade; negative regulation of NF-kappaB transcription factor activity; negative regulation of NIK/NF-kappaB signaling; negative regulation of p38MAPK cascade; negative regulation of type I interferon production; nucleotide-binding oligomerization domain containing signaling pathway; positive regulation of extrinsic apoptotic signaling pathway; protein deubiquitination; protein K63-linked deubiquitination; protein linear deubiquitination; regulation of cilium assembly; regulation of inflammatory response; regulation of intrinsic apoptotic signaling pathway; regulation of microtubule cytoskeleton organization; regulation of mitotic cell cycle; regulation of necroptotic process; regulation of tumor necrosis factor-mediated signaling pathway; ubiquitin-dependent protein catabolic process; Wnt signaling pathway
Disease: Brooke-spiegler Syndrome; Cylindromatosis, Familial; Frontotemporal Dementia And/or Amyotrophic Lateral Sclerosis 8; Trichoepithelioma, Multiple Familial, 1
Reference #:  Q9NQC7 (UniProtKB)
Alt. Names/Synonyms: BRSS; CDMT; CYLD; CYLD lysine 63 deubiquitinase; CYLD1; CYLDI; cylindromatosis (turban tumor syndrome); Deubiquitinating enzyme CYLD; EAC; FLJ20180; FLJ31664; FLJ78684; HSPC057; KIAA0849; MFT; MFT1; Probable ubiquitin carboxyl-terminal hydrolase CYLD; SBS; TEM; Ubiquitin carboxyl-terminal hydrolase CYLD; ubiquitin specific peptidase like 2; Ubiquitin thioesterase CYLD; ubiquitin thiolesterase CYLD; Ubiquitin-specific-processing protease CYLD; USPL2
Gene Symbols: CYLD
Molecular weight: 107,316 Da
Basal Isoelectric point: 5.42  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  Death Receptor Signaling  |  Inhibition of Apoptosis  |  NF-kB Signaling  |  Wnt/ß-Catenin Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein