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Browse CYLD

Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cytoplasm, cytoskeleton, spindle Cytoplasm, cytoskeleton, cilium basal body Note=Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase. During metaphase, it remains localized to the centrosome but is also present along the spindle (PubMed:25134987).
Domain PF01302 CAP-Gly domain
PF00443 Ubiquitin carboxyl-terminal hydrolase
Function

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).

> Gene Ontology
 
Biological Process GO:0000226 microtubule cytoskeleton organization
GO:0001818 negative regulation of cytokine production
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0002218 activation of innate immune response
GO:0002221 pattern recognition receptor signaling pathway
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0006606 protein import into nucleus
GO:0006913 nucleocytoplasmic transport
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007346 regulation of mitotic cell cycle
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0010927 cellular component assembly involved in morphogenesis
GO:0016055 Wnt signaling pathway
GO:0016579 protein deubiquitination
GO:0017038 protein import
GO:0022604 regulation of cell morphogenesis
GO:0030031 cell projection assembly
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030522 intracellular receptor signaling pathway
GO:0031349 positive regulation of defense response
GO:0031503 protein complex localization
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032386 regulation of intracellular transport
GO:0032387 negative regulation of intracellular transport
GO:0032479 regulation of type I interferon production
GO:0032480 negative regulation of type I interferon production
GO:0032606 type I interferon production
GO:0032886 regulation of microtubule-based process
GO:0033157 regulation of intracellular protein transport
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034504 protein localization to nucleus
GO:0034612 response to tumor necrosis factor
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0042306 regulation of protein import into nucleus
GO:0042308 negative regulation of protein import into nucleus
GO:0042345 regulation of NF-kappaB import into nucleus
GO:0042347 negative regulation of NF-kappaB import into nucleus
GO:0042348 NF-kappaB import into nucleus
GO:0042384 cilium assembly
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042992 negative regulation of transcription factor import into nucleus
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0044744 protein targeting to nucleus
GO:0044782 cilium organization
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046823 negative regulation of nucleocytoplasmic transport
GO:0051051 negative regulation of transport
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051224 negative regulation of protein transport
GO:0051493 regulation of cytoskeleton organization
GO:0060070 canonical Wnt signaling pathway
GO:0060271 cilium morphogenesis
GO:0060491 regulation of cell projection assembly
GO:0060759 regulation of response to cytokine stimulus
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0070265 necrotic cell death
GO:0070266 necroptotic process
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070507 regulation of microtubule cytoskeleton organization
GO:0070536 protein K63-linked deubiquitination
GO:0070646 protein modification by small protein removal
GO:0071356 cellular response to tumor necrosis factor
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0090317 negative regulation of intracellular protein transport
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097300 programmed necrotic cell death
GO:0198738 cell-cell signaling by wnt
GO:1900180 regulation of protein localization to nucleus
GO:1900181 negative regulation of protein localization to nucleus
GO:1902017 regulation of cilium assembly
GO:1902115 regulation of organelle assembly
GO:1902532 negative regulation of intracellular signal transduction
GO:1902593 single-organism nuclear import
GO:1903533 regulation of protein targeting
GO:1903828 negative regulation of cellular protein localization
GO:1904589 regulation of protein import
GO:1904590 negative regulation of protein import
GO:1904950 negative regulation of establishment of protein localization
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0004843 thiol-dependent ubiquitin-specific protease activity
GO:0008234 cysteine-type peptidase activity
GO:0019783 ubiquitin-like protein-specific protease activity
GO:0036459 thiol-dependent ubiquitinyl hydrolase activity
GO:0061578 Lys63-specific deubiquitinase activity
GO:0070064 proline-rich region binding
GO:0101005 ubiquitinyl hydrolase activity
Cellular Component GO:0005813 centrosome
GO:0005819 spindle
GO:0005874 microtubule
GO:0005881 cytoplasmic microtubule
GO:0005929 cilium
GO:0009898 cytoplasmic side of plasma membrane
GO:0019897 extrinsic component of plasma membrane
GO:0019898 extrinsic component of membrane
GO:0030496 midbody
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0036064 ciliary basal body
GO:0044441 ciliary part
GO:0097542 ciliary tip
GO:0098552 side of membrane
GO:0098562 cytoplasmic side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04380 Osteoclast differentiation
hsa04622 RIG-I-like receptor signaling pathway
Reactome R-HSA-73887: Death Receptor Signalling
R-HSA-5688426: Deubiquitination
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-168638: NOD1/2 Signaling Pathway
R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling
R-HSA-168643: Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-597592: Post-translational protein modification
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-5357905: Regulation of TNFR1 signaling
R-HSA-162582: Signal Transduction
R-HSA-75893: TNF signaling
R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway
R-HSA-5357786: TNFR1-induced proapoptotic signaling
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CYLD and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CYLD and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
21282461Bladder CarcinomaPromote immunityDegradation of the RIP1 K63 ubiquitin ligases cIAP1/2 amplifies the CD40-mediated cytotoxic effect, whereas inhibition of CYLD, a RIP1 K63 deubiquitinating enzyme, reduces it.
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CYLD in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -1.98; FDR: 0.04110 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CYLD in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1670.559
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2450.851
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1170.894
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1870.585
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4480.817
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1510.955
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2130.601
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2910.858
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1070.954
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9250.479
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2160.552
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1390.102
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CYLD in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277305.5-5.50.572
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275906.8-6.80.304
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CYLD. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CYLD. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CYLD.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CYLD. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CYLD expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CYLD and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCYLD
Namecylindromatosis (turban tumor syndrome)
Aliases KIAA0849; USPL2; ubiquitin specific peptidase like 2; CYLD1; BRSS; CDMT1; CYLDI; EAC; MFT1; SBS; deubiquitin ......
Chromosomal Location16q12.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CYLD collected from DrugBank database.
> Drugs from DrugBank database
 

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