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CYLD Gene

protein-coding   GIFtS: 72
GCID: GC16P050775

Cylindromatosis (Turban Tumor Syndrome)


(Previous symbol: CYLD1)
  See CYLD-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cylindromatosis (Turban Tumor Syndrome)1 2     CYLDI2
CYLD11 2 3     MFT2
Ubiquitin Specific Peptidase Like 21 2     SBS2
Deubiquitinating Enzyme CYLD2 3     TEM2
Ubiquitin Thioesterase CYLD2 3     USPL22
Ubiquitin-Specific-Processing Protease CYLD2 3     Probable Ubiquitin Carboxyl-Terminal Hydrolase CYLD2
BRSS2 5     Ubiquitin Carboxyl-Terminal Hydrolase CYLD2
CDMT2 5     Ubiquitin Thiolesterase CYLD2
EAC2 5     EC 3.4.19.123
MFT12 5     EC 3.1.2.158
KIAA08493 5     

External Ids:    HGNC: 25841   Entrez Gene: 15402   Ensembl: ENSG000000837997   OMIM: 6050185   UniProtKB: Q9NQC73   

Export aliases for CYLD gene to outside databases

Previous GC identifers: GC16P041189 GC16P050823 GC16P050505 GC16P050554 GC16P049333 GC16P036663


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CYLD Gene:
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)

GeneCards Summary for CYLD Gene:
CYLD (cylindromatosis (turban tumor syndrome)) is a protein-coding gene. Diseases associated with CYLD include familial cylindromatosis, and brooke-spiegler syndrome. GO annotations related to this gene include ubiquitin-specific protease activity and protein kinase binding.

UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7
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)

Gene Wiki entry for CYLD Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000016.9  NT_010498.16  NC_018927.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CYLD gene promoter:
         p53   AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCYLD promoter sequence
   Search Chromatin IP Primers for CYLD

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CYLD


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 16q12.1   Ensembl cytogenetic band:  16q12.1   HGNC cytogenetic band: 16q12-q13

CYLD Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CYLD gene location

GeneLoc information about chromosome 16         GeneLoc Exon Structure

GeneLoc location for GC16P050775:  view genomic region     (about GC identifiers)

Start:
50,775,961 bp from pter      End:
50,835,846 bp from pter
Size:
59,886 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7 (See protein sequence)
Recommended Name: Ubiquitin carboxyl-terminal hydrolase CYLD  
Size: 956 amino acids; 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 and Proteopedia for CYLD:
1IXD (3D)        1WHL (3D)        1WHM (3D)        2VHF (3D)    
Secondary accessions: O94934 Q7L3N6 Q96EH0 Q9NZX9
Alternative splicing: 2 isoforms:  Q9NQC7-1   Q9NQC7-2   

Explore the universe of human proteins at neXtProt for CYLD: NX_Q9NQC7

Explore proteomics data for CYLD at MOPED

Post-translational modifications: 

  • Phosphorylated on several serine residues by IKKA and/or IKKB in response to immune stimuli. Phosphorylation
    requires IKBKG. Phosphorylation abolishes TRAF2 deubiquitination, interferes with the activation of Jun kinases,
    and strongly reduces CD40-dependent gene activation by NF-kappa-B1
  • Ubiquitination2 at Lys10, Lys114, Lys121, Lys132, Lys708
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for CYLD (Q9NQC7) (see all 12)
     PVQESPP  TGSTSDPG  LLHINDIIP  KVTSPYWEER 


    See CYLD Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001035814.1  NP_001035877.1  NP_056062.1  

    ENSEMBL proteins: 
     ENSP00000457108   ENSP00000457576   ENSP00000308928   ENSP00000454515   ENSP00000462134  
     ENSP00000456912   ENSP00000455535   ENSP00000381574   ENSP00000392025   ENSP00000456488  
     ENSP00000463197   ENSP00000458507   ENSP00000445447  
    Reactome Protein details: Q9NQC7

    CYLD Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for CYLD
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Proteins for CYLD
    OriGene Protein Over-expression Lysate for CYLD
    OriGene MassSpec for CYLD
    OriGene Custom Protein Services for CYLD
    GenScript Custom Purified and Recombinant Proteins Services for CYLD
    Novus Biologicals CYLD Protein
    Novus Biologicals CYLD Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for CYLD

     
    Search eBioscience for Proteins for CYLD 

    CYLD Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of CYLD
    Browse R&D Systems for Antibodies
    Cell Signaling Technology (CST) Antibodies for CYLD 
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    OriGene Custom Antibody Services for CYLD
    Novus Biologicals CYLD Antibodies
    Abcam antibodies for CYLD
    Cloud-Clone Corp. Antibodies for CYLD
    ThermoFisher Antibody for CYLD
    LSBio Antibodies in human, mouse, rat for CYLD

    CYLD Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for CYLD
    Cloud-Clone Corp. CLIAs for CYLD
    Search eBioscience for ELISAs for CYLD 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR001394 Peptidase_C19_UCH
     IPR000938 CAP-Gly_domain
     IPR018200 Pept_C19ubi-hydrolase_C_CS
     IPR028889 UCH/PAN2

    Graphical View of Domain Structure for InterPro Entry Q9NQC7

    ProtoNet protein and cluster: Q9NQC7

    2 Blocks protein domains:
    IPB000938 CAP-Gly domain
    IPB001394 Ubiquitin thiolesterase


    UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7
    Similarity: Belongs to the peptidase C19 family
    Similarity: Contains 3 CAP-Gly domains
    Similarity: Contains 1 USP domain


    Find genes that share domains with CYLD           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CYLD_HUMAN, Q9NQC7
    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)
    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)
    Enzyme regulation: Inhibited by phosphorylation at serine residues

         Enzyme Numbers (IUBMB): EC 3.1.2.152 EC 3.4.19.121

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003735NOT structural constituent of ribosome IBA--
    GO:0004221ubiquitin thiolesterase activity ----
    GO:0004843ubiquitin-specific protease activity IDA18313383
    GO:0005515protein binding IPI18636086
    GO:0008270zinc ion binding IDA18313383
         
    Find genes that share ontologies with CYLD           About GenesLikeMe


    Phenotypes:
         7 GenomeRNAi human phenotypes for CYLD:
     Cell cycle / mitosis defect  Increased ID2::GFP protein exp  Increased NF-kappaB reporter a  Increased cell death HMECs cel 
     Increased mitotic index  Synthetic lethal with Ras  Upregulation of NF-kappaB path 

         14 MGI mutant phenotypes (inferred from 9 alleles(MGI details for Cyld):
     behavior/neurological  cellular  digestive/alimentary  endocrine/exocrine gland  growth/size/body 
     hematopoietic system  homeostasis/metabolism  immune system  integument  limbs/digits/tail 
     mortality/aging  normal  respiratory system  tumorigenesis 

    Find genes that share phenotypes with CYLD           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for CYLD: Cyldtm1.1Gmos Cyldtm1Scs Cyldtm1Jdgl Cyldtm1.1Awai Cyldtm1Lex

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CYLD
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for CYLD

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CYLD
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CYLD

    miRNA
    Products:
        
    miRTarBase miRNAs that target CYLD:
    hsa-mir-197-3p (MIRT004211), hsa-mir-182-5p (MIRT006978), hsa-mir-320a (MIRT044462), hsa-mir-181b-5p (MIRT005595)

    Block miRNA regulation of human, mouse, rat CYLD using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CYLD (see all 107):
    hsa-miR-582-3p hsa-miR-579 hsa-miR-3194-5p hsa-miR-15a hsa-miR-106a hsa-miR-30d hsa-miR-371-5p hsa-miR-4267
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for CYLD
    Predesigned siRNA for gene silencing in human, mouse, rat CYLD

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for CYLD

    Clone
    Products:
         
    OriGene clones in human, mouse for CYLD (see all 19)
    OriGene ORF clones in mouse, rat for CYLD
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): CYLD (NM_001042412)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CYLD
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CYLD
    Addgene plasmids for CYLD 

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    Browse ESI BIO Cell Lines and PureStem Progenitors for CYLD 
    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYLD


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CYLD_HUMAN, Q9NQC7: Cytoplasm. Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton. Cell membrane; Peripheral
    membrane protein; Cytoplasmic side. Note=Detected at the microtubule cytoskeleton during interphase. Detected at
    the midbody during telophase
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    cytosol5
    plasma membrane5
    nucleus2
    endoplasmic reticulum1
    extracellular1
    lysosome1
    peroxisome1
    vacuole1

    Gene Ontology (GO): Selected cellular component terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005813centrosome IDA--
    GO:0005829cytosol TAS--
    GO:0005881colocalizes with cytoplasmic microtubule IDA17495026

    Find genes that share ontologies with CYLD           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CYLD About   (see all 9)  
    See pathways by source

    SuperPathContained pathways About
    1RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways0.47
    Negative regulators of RIG-I/MDA5 signaling0.42
    RIG-I-like receptor signaling pathway0.47
    2Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways0.68
    NOD1/2 Signaling Pathway0.68
    3Wnt / Hedgehog / Notch
    Wnt / Hedgehog / Notch
    4TNF receptor signaling pathway
    TNF receptor signaling pathway
    5TNF-alpha/NF-kB Signaling Pathway
    TNF-alpha/NF-kB Signaling Pathway


    Find genes that share SuperPaths with CYLD           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    3 Cell Signaling Technology (CST) Pathways for CYLD
        Wnt / Hedgehog / Notch
    NF-kappaB Signaling
    Protein Stability

    3 BioSystems Pathways for CYLD
        TNF-alpha/NF-kB Signaling Pathway
    Canonical NF-kappaB pathway
    TNF receptor signaling pathway

    2 Reactome Pathways for CYLD
        Negative regulators of RIG-I/MDA5 signaling
    NOD1/2 Signaling Pathway


    2 Kegg Pathways  (Kegg details for CYLD):
        Osteoclast differentiation
    RIG-I-like receptor signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CYLD: 
              Antiviral Response in human mouse rat
              Necrosis in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat
              Cell Death PathwayFinder in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CYLD

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CYLD (Q9NQC71, 2, 3 ENSP000003089284) via UniProtKB, MINT, STRING, and/or I2D (see all 54)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TUBA1AQ71U361, 2, 3, ENSP000003010714EBI-2117940,EBI-302552 MINT-7562676 MINT-7561617 MINT-7563186 MINT-7623764 MINT-7679557 MINT-7561703 MINT-7679902 I2D: score=2 STRING: ENSP00000301071
    HDAC6Q9UBN71, 2, 3, ENSP000003340614EBI-2117940,EBI-301697 MINT-7565823 MINT-7564471 MINT-7680083 MINT-7679902 I2D: score=3 STRING: ENSP00000334061
    TBK1Q9UHD22, 3, ENSP000003299674MINT-6804616 I2D: score=3 STRING: ENSP00000329967
    ITCHQ96J021, 3, ENSP000003639984EBI-2117940,EBI-1564678 I2D: score=2 STRING: ENSP00000363998
    DDX58O957861, 2, 3, ENSP000003692134EBI-2117940,EBI-995350 MINT-6804571 MINT-6804584 I2D: score=4 STRING: ENSP00000369213
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002181NOT cytoplasmic translation IBA--
    GO:0006511ubiquitin-dependent protein catabolic process IEA--
    GO:0007049cell cycle IEA--
    GO:0007346regulation of mitotic cell cycle IMP17495026
    GO:0016055Wnt signaling pathway IEA--

    Find genes that share ontologies with CYLD           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CYLD

    1 HMDB Compound for CYLD    About this table
    CompoundSynonyms CAS #PubMed Ids
    WaterDihydrogen oxide (see all 2)7732-18-5--

    3 Novoseek inferred chemical compound relationships for CYLD gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cdmt 88.5 32 9057978 (7), 10376887 (7), 8737962 (4), 9928683 (2)
    cdcl2 42.7 9 9057978 (7)
    aspirin 25.2 1 15029443 (1)



    Find genes that share compounds with CYLD           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for CYLD gene (3 alternative transcripts): 
    NM_001042355.1  NM_001042412.1  NM_015247.2  

    Unigene Cluster for CYLD:

    Cylindromatosis (turban tumor syndrome)
    Hs.578973  [show with all ESTs]
    Unigene Representative Sequence: NM_015247
    17 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000569681 ENST00000569418(uc002egn.1) ENST00000569891(uc002ego.3)
    ENST00000311559 ENST00000564326 ENST00000566206(uc021tic.1 uc010cbs.1)
    ENST00000566679 ENST00000564634 ENST00000398568 ENST00000427738(uc021tib.1)
    ENST00000568704 ENST00000563629(uc002egs.1) ENST00000563976 ENST00000562884
    ENST00000566024 ENST00000568744 ENST00000540145(uc002egp.1 uc002egq.1 uc002egr.1)

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate CYLD (see all 107):
    hsa-miR-582-3p hsa-miR-579 hsa-miR-3194-5p hsa-miR-15a hsa-miR-106a hsa-miR-30d hsa-miR-371-5p hsa-miR-4267
    Browse SwitchGear 3'UTR luciferase reporter plasmids
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    GenScript: all cDNA clones in your preferred vector (see all 3): CYLD (NM_001042412)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CYLD
    Addgene plasmids for CYLD 
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    OriGene qPCR primer pairs and template standards for CYLD
    OriGene qSTAR qPCR primer pairs in human, mouse for CYLD
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat CYLD
      QuantiTect SYBR Green Assays in human, mouse, rat CYLD
      QuantiFast Probe-based Assays in human, mouse, rat CYLD

    Additional mRNA sequence: 

    AF161542.1 AJ250014.1 AK000187.1 AK024212.1 AK024348.1 AK056226.1 AK225202.1 AK292975.1 
    AK310832.1 AL050166.1 BC012342.1 FN823255.1 FN823256.1 

    14 DOTS entries:

    DT.91863285  DT.445138  DT.95141924  DT.40193024  DT.104981  DT.441097  DT.100820458  DT.100033725 
    DT.86854073  DT.120727728  DT.91703675  DT.101976017  DT.40114516  DT.97785369 

    Selected AceView cDNA sequences (see all 263):

    CB241377 BM699172 CD678606 BM832976 CA445743 CD673004 BC012342 BI917711 
    AA044899 BQ006009 AV726868 AI089691 CK819105 AA699316 BM719060 BX378855 
    BG180100 AK024212 AW469427 AK000187 CD742887 CA447364 BM311793 CB053977 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for CYLD (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b · 10c ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^
    SP1:                    -                                                                       -                                               -               
    SP2:                                -                                                           -                                               -               
    SP3:                                                                                            -                                                               
    SP4:                                                                                                                                                            
    SP5:                                                                                            -     -                                                         

    ExUns: 18a · 18b ^ 19 ^ 20a · 20b ^ 21a · 21b · 21c
    SP1:                          -                     
    SP2:                          -                     
    SP3:                                                
    SP4:                                                
    SP5:                                                


    ECgene alternative splicing isoforms for CYLD

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CYLD expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGAATCTCTT
    CYLD Expression
    About this image


    CYLD expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 3 entries
             Hindgut
     
     Thymus (Hematopoietic System)
             T Helper Cells Thymus
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Blood (Cardiovascular System)
             T Helper Cells Thymus
    CYLD Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CYLD Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.578973

    UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7
    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

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CYLD: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for CYLD gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cyld1 , 5 cylindromatosis (turban tumor syndrome)1, 5 89.81(n)1
    94.87(a)1
      8 (43.51 cM)5
    742561  NM_001128170.21  NP_001121642.11 
     886970285 
    chicken
    (Gallus gallus)
    Aves CYLD1 cylindromatosis (turban tumor syndrome) 81.57(n)
    87.93(a)
      415725  XM_004944175.1  XP_004944232.1 
    lizard
    (Anolis carolinensis)
    Reptilia CYLD6
    cylindromatosis (turban tumor syndrome)
    81(a)
    1 ↔ 1
    GL343227.1(1170436-1189173)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.114462 Xenopus laevis transcribed sequence with weak similarity more 75.46(n)    AW640982.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.183432 Transcribed sequence with weak similarity to protein more 77.02(n)    BQ260477.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG56033
    CYLD1
    transcription factor3
    cylindromatosis1
    45(a)3
    54.16(n)1
    48.28(a)1
      343801  NM_164911.11  NP_723556.11 
    worm
    (Caenorhabditis elegans)
    Secernentea F40F12.5a3 Ubiquitin carboxyl-terminal hydrolases
    family more
    35(a)   III(9970710-9982367)   --


    ENSEMBL Gene Tree for CYLD (if available)
    TreeFam Gene Tree for CYLD (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CYLD gene
    1 SIMAP similar gene for CYLD using alignment to 13 protein entries:     CYLD_HUMAN (see all proteins):
    DCTN1

    Find genes that share paralogs with CYLD           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CYLD (see all 1158)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 16 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0459674
    Multiple familial trichoepithelioma 1 (MFT1)4--see VAR_0459672 E G mis40--------
    rs1471806041,2
    C--36673399(+) AGTAG-/ACAAA 
            
    ACAAA
    3 -- int10--------
    rs727963761,2
    --36673408(+) AACAAA/GACAAG 3 -- int10--------
    rs1407641591,2
    C--36676272(+) ACATA-/TGTGTGT 3 -- int10--------
    rs1870156261,2
    --36683112(+) CTATCA/TATATC 3 -- int10--------
    rs779109491,2
    C--36683115(+) TCTATA/CTCTTT 3 -- int10--------
    rs596163681,2
    C--50774339(+) ACAAA-/AAGAAGGG 3 -- us2k10--------
    rs58167191,2
    C--50774941(+) TAAAa-/AC/ACA
    C
    /ACACAC
    acaca
    6 -- us2k1 cds10--------
    rs129292221,2
    --50789050(+) cacgtA/Gtacat 3 -- int10--------
    rs129292341,2
    F--50789062(+) tgtgtG/Atatat 3 -- int11Minor allele frequency- A:0.04NA 120

    HapMap Linkage Disequilibrium report for CYLD (50775961 - 50835846 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for CYLD:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2714463CNV Deletion23290073
    esv2714464CNV Deletion23290073

    Human Gene Mutation Database (HGMD): CYLD
    2 Site Specific Mutation Identification with PCR Assays for CYLD:
    Cosmic IdAA Change
    21988p.R758*
    21989p.Q905*
    SeqTarget long-range PCR primers for resequencing CYLD
    DNA2.0 Custom Variant and Variant Library Synthesis for CYLD

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 605018   
    OMIM disorders: 132700  605041  601606  
    UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7
  • Cylindromatosis, 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
  • Multiple 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
  • Brooke-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

  • 5 diseases for CYLD:    
    About MalaCards
    familial cylindromatosis    brooke-spiegler syndrome    multiple familial trichoepithelioma    multiple familial trichoepithelioma 1
    spiradenoma

    2 diseases from the University of Copenhagen DISEASES database for CYLD:
    Brooke-Spiegler syndrome     Spiradenoma

    Find genes that share disorders with CYLD           About GenesLikeMe

    6 Novoseek inferred disease relationships for CYLD gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cylindromatosis, familial 98.6 17 12917689 (1), 14585643 (1), 15024746 (1), 18245814 (1) (see all 16)
    carcinoma adenoid cystic 88.3 9 18008375 (1), 18234730 (1), 12023583 (1), 19462465 (1) (see all 7)
    somatic mutations 47 4 11756779 (2), 19668078 (1), 10835629 (1)
    tumors 33.1 34 20227366 (3), 16774947 (3), 17851586 (2), 19730223 (2) (see all 18)
    necrosis 4.14 4 18245814 (1), 15226292 (1), 17851586 (1), 18636086 (1)
    cancer 0 2 15024746 (1), 18008375 (1)

    Genetic Association Database (GAD): CYLD
    Human Genome Epidemiology (HuGE) Navigator: CYLD (3 documents)

    Export disorders for CYLD gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CYLD gene, integrated from 10 sources (see all 160):
    (articles sorted by number of sources associating them with CYLD)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin. (PubMed id 19893491)1, 2, 9 Wickstrom S.A.... Massoumi R. (EMBO J. 2010)
    2. CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. (PubMed id 12917689)1, 2, 9 Trompouki E.... Mosialos G. (Nature 2003)
    3. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. (PubMed id 18636086)1, 2, 9 Friedman C.S.... Ting A.T. (EMBO Rep. 2008)
    4. Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl. (PubMed id 20227366)1, 2, 9 Tauriello D.V.... Maurice M.M. (Mol. Cell 2010)
    5. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. (PubMed id 12917690)1, 2, 9 Brummelkamp T.R.... Bernards R. (Nature 2003)
    6. A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome. (PubMed id 14632188)1, 2, 9 Hu G....Celebi J.T. (J. Invest. Dermatol. 2003)
    7. Identification of the familial cylindromatosis tumor suppressor gene. (PubMed id 10835629)1, 2, 9 Bignell G.R.... Stratton M.R. (Nat. Genet. 2000)
    8. Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation. (PubMed id 15870263)1, 2, 9 Reiley W.... Sun S.C. (Mol. Cell. Biol. 2005)
    9. Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy. (PubMed id 22019778)1, 4 Zhang F....Zhang X. (Nat. Genet. 2011)
    10. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1540 HGNC: 2584 AceView: CYLD Ensembl:ENSG00000083799 euGenes: HUgn1540
    ECgene: CYLD Kegg: 1540 H-InvDB: CYLD

    (According to HUGE)
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    HUGE: KIAA0849

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for CYLD Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CYLD Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CYLD gene:
    Search GeneIP for patents involving CYLD

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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