Tbio CYLD Ubiquitin carboxyl-terminal hydrolase CYLD

Protein Summary

Description

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 (PubMed:18636086, PubMed:26670046, PubMed:27458237, PubMed:26997266, PubMed:27591049, PubMed:29291351, PubMed:18313383). Plays an important role in the regulation of pathways leading to NF-kappa-B activation (PubMed:12917689, PubMed:12917691). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (PubMed:12917690). Negative regulator of Wnt signaling (PubMed:20227366). 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:18222923, PubMed:20194890). Required for normal cell cycle progress and normal cytokinesis (PubMed:17495026, PubMed:19893491). Inhibits nuclear translocation of NF-kappa-B (PubMed:18636086). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (PubMed:18636086). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (By similarity). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). 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 (By similarity). 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 (PubMed:26997266, PubMed:26670046, PubMed:27458237, PubMed:27591049). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (PubMed:26997266). Involved in TNF-alpha-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (By similarity). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:29291351). This gene is encodes a cytoplasmic protein with three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains that functions as a deubiquitinating enzyme. Mutations in this gene have been associated with cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9NQC7
• O94934
• Q7L3N6
• Q96EH0
• Q9NZX9

Gene Name

• CYLD

Ensembl ID

• ENST00000311559
• ENSP00000308928
• ENSG00000083799
• ENST00000398568
• ENSP00000381574
• ENST00000427738
• ENSP00000392025
• ENST00000564326
• ENSP00000454515
• ENST00000569418
• ENSP00000457576

Symbol

• CYLD1
• KIAA0849
• EAC
• MFT
• SBS
• TEM
• BRSS
• CDMT
• MFT1
• CYLD1
• CYLDI
• USPL2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
biological process	0.99
hub protein	0.99
transcription factor perturbation	0.94
virus perturbation	0.94

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Ribosomal Protein / Ubiquitin Carboxyl-terminal Hydrolase Cyld

Protein / ... / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase Cyld

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase Cyld

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 662.94   (req: < 5)

Gene RIFs: 206   (req: <= 3)

Antibodies: 267   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 662.94   (req: >= 5)

Gene RIFs: 206   (req: > 3)

Antibodies: 267   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 38

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0