======= CYLD =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CYLD
  * **<color #00a2e8>Official Name</color>**: CYLD lysine 63 deubiquitinase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1540|1540]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9NQC7|Q9NQC7]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CYLD&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CYLD|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605018|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|CAP GLY|
|UCH|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|negative regulation of NF-kappaB transcription factor activity|
|positive regulation of T cell differentiation|
|positive regulation of lymphocyte differentiation|
|thiol-dependent ubiquitin-specific protease activity|
|regulation of NIK/NF-kappaB signaling|
|spindle|
|regulation of type I interferon production|
|pattern recognition receptor signaling pathway|
|T cell differentiation|
|ciliary basal body|
|regulation of T cell differentiation|
|positive regulation of leukocyte differentiation|
|regulation of extrinsic apoptotic signaling pathway|
|midbody|
|regulation of intrinsic apoptotic signaling pathway|
|negative regulation of DNA-binding transcription factor activity|
|intracellular receptor signaling pathway|
|regulation of cytokine-mediated signaling pathway|
|negative regulation of MAPK cascade|
|regulation of lymphocyte differentiation|
|positive regulation of apoptotic signaling pathway|
|negative regulation of canonical Wnt signaling pathway|
|regulation of response to cytokine stimulus|
|regulation of JNK cascade|
|positive regulation of hemopoiesis|
|regulation of microtubule cytoskeleton organization|
|homeostasis of number of cells|
|regulation of plasma membrane bounded cell projection assembly|
|positive regulation of T cell activation|
|regulation of cell projection assembly|
|regulation of B cell activation|
|negative regulation of Wnt signaling pathway|
|positive regulation of leukocyte cell-cell adhesion|
|regulation of protein binding|
|regulation of organelle assembly|
|regulation of microtubule-based process|
|regulation of stress-activated MAPK cascade|
|innate immune response-activating signal transduction|
|T cell activation|
|regulation of stress-activated protein kinase signaling cascade|
|lymphocyte differentiation|
|cell fate commitment|
|positive regulation of cell-cell adhesion|
|activation of innate immune response|
|regulation of leukocyte differentiation|
|negative regulation of cytokine production|
|protein deubiquitination|
|regulation of canonical Wnt signaling pathway|
|regulation of leukocyte cell-cell adhesion|
|protein modification by small protein removal|
|regulation of T cell activation|
|positive regulation of cellular protein localization|
|leukocyte differentiation|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|Wnt signaling pathway|
|cell-cell signaling by wnt|
|positive regulation of lymphocyte activation|
|regulation of Wnt signaling pathway|
|positive regulation of response to biotic stimulus|
|regulation of binding|
|lymphocyte activation|
|regulation of apoptotic signaling pathway|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|positive regulation of cell activation|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of DNA-binding transcription factor activity|
|negative regulation of phosphorylation|
|regulation of hemopoiesis|
|regulation of innate immune response|
|protein kinase binding|
|positive regulation of defense response|
|centrosome|
|negative regulation of intracellular signal transduction|
|positive regulation of multi-organism process|
|regulation of lymphocyte activation|
|regulation of response to biotic stimulus|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|modification-dependent macromolecule catabolic process|
|hemopoiesis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|immune response-activating signal transduction|
|proteolysis involved in cellular protein catabolic process|
|negative regulation of protein modification process|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|hematopoietic or lymphoid organ development|
|cellular protein catabolic process|
|activation of immune response|
|regulation of mitotic cell cycle|
|regulation of cell activation|
|positive regulation of apoptotic process|
|immune system development|
|positive regulation of programmed cell death|
|regulation of cell adhesion|
|protein catabolic process|
|regulation of plasma membrane bounded cell projection organization|
|regulation of cytokine production|
|perinuclear region of cytoplasm|
|positive regulation of cell death|
|regulation of cell projection organization|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|regulation of defense response|
|innate immune response|
|regulation of multi-organism process|
|zinc ion binding|
|positive regulation of immune response|
|cellular macromolecule catabolic process|
|regulation of cellular localization|
|leukocyte activation|
|defense response to other organism|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|protein modification by small protein conjugation or removal|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|cell activation|
|cell death|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|cell-cell signaling|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|negative regulation of signal transduction|
|proteolysis|
|regulation of organelle organization|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|cell cycle|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|regulation of protein phosphorylation|
|regulation of response to stress|
|regulation of apoptotic process|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|negative regulation of response to stimulus|
|homeostatic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|immune response|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

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

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:s:spata2|SPATA2]]|0.401|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 11761
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.96 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CYLD Expression in NALM6 Cells: 4.96'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>