Gene content    
CYLD ( by HUGO)
Cylindromatosis (Turban Tumor Syndrome)
Tumor suppressor gene
Cylindromatosis (Turban Tumor Syndrome)
CYLD1
Ubiquitin Specific Peptidase Like 2
Deubiquitinating Enzyme CYLD
Ubiquitin Thioesterase CYLD
Ubiquitin-Specific-Processing Protease CYLD
BRSS
CDMT
EAC
MFT1
KIAA0849
CYLDI
MFT
SBS
TEM
USPL2
Probable Ubiquitin Carboxyl-Terminal Hydrolase CYLD
Ubiquitin Carboxyl-Terminal Hydrolase CYLD
Ubiquitin Thiolesterase CYLD
EC 3.4.19.12
EC 3.1.2.15
NCBI: 16q12.1    Ensembl: 16q12.1
CYLD_HUMANSize: 956 amino acidsMass: 107316 Da

  • Subunit: 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 (By similarity) Sequence caution: Sequence=AAF29029.1; Type=Frameshift; Positions=776, 808, 932; Sequence=BAA74872.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; 4 PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for CYLD: 1IXD (3D) [IMAGE] 1WHL (3D) [IMAGE] 1WHM (3D) [IMAGE] 2VHF (3D) [IMAGE]
  • Tissue specificity: 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 [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays
  • Function:
    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 (By similarity)
                          
    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 (By similarity)
  • Catalytic activity:
    Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal)
  • Similarity:
    Belongs to the peptidase C19 family
                          
    Contains 3 CAP-Gly domains
                          
    Contains 1 USP domain [IMAGE]
  • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR000938CAP-Gly_domainCAP-GlyDomain
    IPR001394Peptidase_C19_UCHPeptidase C19, ubiquitin carboxyl-terminal hydrolase 2Family
    BlocksIPB001394Ubiquitin thiolesteraseUbiquitin thiolesterase, family 2

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process negative regulation of NF-kappaB import into nucleus IDA GOA 18313383
    negative regulation of NF-kappaB transcription factor activity IDA GOA 18313383
    protein K63-linked deubiquitination IDA GOA 18313383
    regulation of mitotic cell cycle IMP GOA 17495026
    Cellular Component colocalizes_with cytoplasmic microtubule IDA GOA 17495026
    colocalizes_with midbody IDA GOA 17495026
    cytosol IDA GOA 18313383
    Molecular Function proline-rich region binding IPI GOA 15341735
    protein binding IPI GOA 18636086
    protein kinase binding IPI GOA 17495026
    ubiquitin-specific protease activity IDA GOA 18313383
    zinc ion binding IDA GOA 18313383

    Disorder & Mutation    
    Source Disease
    SWISS-PROTCylindromatosis, familial (FCYL) [MIM:132700]: A disorder characterized by multiple skin tumors that develop from skin appendages, such as hair follicles and sweat glands. Affected individuals typically develop large numbers of tumors called cylindromas that arise predominantly in hairy parts of the body with approximately 90% on the head and neck. In severely affected individuals, cylindromas may combine into a confluent mass which may ulcerate or become infected (turban tumor syndrome). Individuals with familial cylindromatosis occasionally develop other types of tumors including spiradenomas that begin in sweat glands, and trichoepitheliomas arising from hair follicles. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTMultiple familial trichoepithelioma 1 (MFT1) [MIM:601606]: Autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTBrooke-Spiegler syndrome (BRSS) [MIM:605041]: An autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life. Note=The disease is caused by mutations affecting the gene represented in this entry

    CYLD cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene