CYLD

Gene Information

Official Symbol: CYLD
Official Name: CYLD lysine 63 deubiquitinase
Aliases and Previous Symbols: N/A
Entrez ID: 1540
UniProt: Q9NQC7
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: 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 Summary: Deubiquitinase 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 (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. 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. 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). Also able to remove linear ('Met-1'-linked) polyubiquitin chains to regulate innate immunity: recruited to the LUBAC complex and, together with OTULIN, restricts linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (PubMed:26670046, PubMed:26997266). {ECO:0000250|UniProtKB:Q80TQ2, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:12917690, ECO:0000269|PubMed:12917691, ECO:0000269|PubMed:14676304, ECO:0000269|PubMed:17495026, ECO:0000269|PubMed:18222923, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19893491, ECO:0000269|PubMed:20194890, ECO:0000269|PubMed:20227366, ECO:0000269|PubMed:26670046, ECO:0000269|PubMed:26997266}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Dexamethasone 0.006 to 0.015μM on day4 R07 exp352	-2.86
Dexamethasone 0.006μM R07 exp351	-2.62
Bortezomib 0.005μM R00 exp6	-2.19
Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307	-2.17
Citral 75μM R06 exp275	-2.08
Hippuristanol 0.12μM R08 exp488	-2.08
Arsenic trioxide 60μM R08 exp449	-2.01
Genistein 15μM R07 exp360	-1.95
Artemisinin 50μM R08 exp450	-1.94
BH1 1μM R04 exp169	-1.93
Rapamycin 2μM plus FK-506 5μM R07 exp308	-1.86
Selumetinib 20μM R02 exp81	-1.8
Hippuristanol 0.12μM R08 exp489 no dilution day6	-1.8
GSK-J4 1.5μM R08 exp441	1.73
THZ531 0.225μM R08 exp444	1.81
Cytochalasin-B 5μM R07 exp349	1.88
JQ1 0.8μM R08 exp435	2.45

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 11761
Expression level (log2 read counts): 4.96

Expression Distribution

CAP GLY
UCH

ripoptosome assembly
ripoptosome assembly involved in necroptotic process
protein linear deubiquitination
negative regulation of p38MAPK cascade
Lys63-specific deubiquitinase activity
positive regulation of T cell receptor signaling pathway
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
Lys48-specific deubiquitinase activity
regulation of necroptotic process
proline-rich region binding
regulation of programmed necrotic cell death
T cell lineage commitment
negative regulation of NIK/NF-kappaB signaling
positive regulation of antigen receptor-mediated signaling pathway
necroptotic process
positive T cell selection
regulation of B cell differentiation
nucleotide-binding oligomerization domain containing signaling pathway
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
programmed necrotic cell death
regulation of necrotic cell death
necrotic cell death
protein K63-linked deubiquitination
protein K48-linked deubiquitination
cytoplasmic pattern recognition receptor signaling pathway
negative regulation of JNK cascade
regulation of T cell receptor signaling pathway
T cell selection
regulation of p38MAPK cascade
negative regulation of stress-activated MAPK cascade
negative regulation of stress-activated protein kinase signaling cascade
negative regulation of type I interferon production
ciliary tip
positive regulation of extrinsic apoptotic signaling pathway
cytoplasmic microtubule
thiol-dependent ubiquitinyl hydrolase activity
regulation of tumor necrosis factor-mediated signaling pathway
extrinsic component of cytoplasmic side of plasma membrane
regulation of antigen receptor-mediated signaling pathway
regulation of cilium assembly