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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CYLD Gene

protein-coding   GIFtS: 71
GCID: GC16P050775

cylindromatosis (turban tumor syndrome)


(Previous symbol: CYLD1)
 Explore 21 diseases affiliated with
CYLD via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for CYLD    

Aliases
for CYLD gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Cylindromatosis (Turban Tumor Syndrome)1 2     CYLDI2
CYLD11 2 3 5     MFT2
USPL21 2     SBS2
KIAA08491 3     TEM2
Deubiquitinating Enzyme CYLD2 3     Probable Ubiquitin Carboxyl-Terminal Hydrolase CYLD2
Ubiquitin Thioesterase CYLD2 3     Ubiquitin Carboxyl-Terminal Hydrolase CYLD2
Ubiquitin-Specific-Processing Protease CYLD2 3     Ubiquitin Specific Peptidase Like 22
CDMT2 5     Ubiquitin Thiolesterase CYLD2
EAC2 5     EC 3.4.19.123
MFT12 5     EC 3.1.2.158
BRSS2     

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


Summaries
for CYLD gene

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

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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000016.9  NC_018927.1  NT_010498.15  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the CYLD gene promoter:
         p53   AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: CYLD promoter sequence
   Search SABiosciences Chromatin IP Primers for CYLD

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for CYLD gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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)
Subcellular location: 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
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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q9NQC7

    • 4/12 DME Specific Peptides for CYLD (Q9NQC7) (see all 12)
     PVQESPP  TGSTSDPG  LLHINDIIP  KVTSPYWEER 

    CYLD Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    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
    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 (see all 3): CYLD
    OriGene Protein Over-expression Lysate (see all 2): 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 ProSpec Recombinant Proteins
    Uscn Proteins for CYLD

    Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005829cytosol TAS--
    GO:0005881colocalizes with cytoplasmic microtubule IDA17495026
    GO:0030496colocalizes with midbody IDA17495026
    GO:0031234extrinsic to internal side of plasma membrane IDA--
    GO:0048471perinuclear region of cytoplasm IEA--


    CYLD for ontologies           About GeneDecksing



    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 
    OriGene Antibodies (see all 2): CYLD
    OriGene Custom Antibody Services for CYLD 
    GenScript Custom Superior Antibodies Services for CYLD
    Novus Biologicals CYLD Antibodies
    Abcam antibodies for CYLD 
    Uscn Antibodies for CYLD
    ThermoFisher Antibody for CYLD

    Assay Products for CYLD: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for CYLD
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for CYLD

    Protein Domains /
    Families
    for CYLD gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    CYLD for domains           About GeneDecksing

    3 InterPro domains/families:
     IPR001394 Peptidase_C19
     IPR000938 CAP-Gly_domain
     IPR018200 Pept_C19ubi-hydrolase_C_CS

    Graphical View of Domain Structure for InterPro Entry Q9NQC7

    ProtoNet protein and cluster: Q9NQC7

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


    UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7
    Similarity: Belongs to the peptidase C67 family
    Similarity: Contains 3 CAP-Gly domains


    Function
    for CYLD gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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)
    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

    miRNA
    Products:            		miRTarBase miRNAs that target CYLD:
    hsa-mir-197 (MIRT004211), hsa-mir-181b (MIRT005595)

    OriGene 3'-UTR Clone (see all 3): CYLD
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CYLD
    8/107 QIAGEN miScript miRNA 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
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CYLD (see all 7)
    OriGene shRNA RFP: CYLD
    Browse OriGene siRNA
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CYLD

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

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CYLD (see all 8)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CYLD (see all 4)
    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 

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for CYLD
    Search LifeMap BioReagents cell lines for CYLD

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYLD

    Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004221ubiquitin thiolesterase activity IEA--
    GO:0004843ubiquitin-specific protease activity IDA18636086
    GO:0005515protein binding IPI18636086
    GO:0008270zinc ion binding IDA18313383
    GO:0019901protein kinase binding IPI18636086


    CYLD for ontologies           About GeneDecksing


    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 

    Animal Models:
         Mouse knock-outs for CYLD: Cyldtm1.1Gmos Cyldtm1Scs Cyldtm1Jdgl Cyldtm1.1Awai Cyldtm1Lex
         14 MGI mutant phenotypes (inferred from 9 alleles) (MGI details for Cyld):
     behavior/neurological  cellular  digestive/alimentary  endocrine/exocrine gland  growth/size 
     hematopoietic system  homeostasis/metabolism  immune system  integument  limbs/digits/tail 
     mortality/aging  normal  respiratory system  tumorigenesis 

    CYLD for phenotypes           About GeneDecksing


    Pathways & Interactions
    for CYLD gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/11 super-pathways (see all 11) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    		RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways1.00
    		Negative regulators of RIG-I/MDA5 signaling0.49
    		RIG-I-like receptor signaling pathway0.52
    2Immune System
    		Immune System1.00
    		Innate Immune System0.46
    3Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
    		Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways1.00
    		NOD1/2 Signaling Pathway0.69
    4Wnt / Hedgehog / Notch
    		Wnt / Hedgehog / Notch1.00
    5Protein Stability
    		Protein Stability1.00

    Pathway sources
    See GeneCards unified pathways
    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
    TNF receptor signaling pathway
    Canonical NF-kappaB pathway

    5/7        Reactome Pathways for CYLD (see all 7)
        RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    CYLD mediated deubiquitination of RIG-I
    NOD1/2 Signaling Pathway
    Negative regulators of RIG-I/MDA5 signaling
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways


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


    CYLD for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for CYLD

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

    5/50 Interacting proteins for CYLD (Q9NQC72, 3 ENSP000003089284) via UniProtKB, MINT, STRING, and/or I2D (see all 50)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HDAC6Q9UBN72, 3, ENSP000003340614MINT-7565823 MINT-7564471 MINT-7680083 MINT-7679902 I2D: score=3 STRING: ENSP00000334061
    TBK1Q9UHD22, 3, ENSP000003299674MINT-6804616 I2D: score=3 STRING: ENSP00000329967
    TUBA1AQ71U362, 3, ENSP000003010714MINT-7562676 MINT-7561617 MINT-7563186 MINT-7623764 MINT-7679557 MINT-7561703 MINT-7679902 I2D: score=2 STRING: ENSP00000301071
    DDX58O957862, 3, ENSP000003692134MINT-6804571 MINT-6804584 I2D: score=4 STRING: ENSP00000369213
    UBCP0CG482, 3, ENSP000003448184MINT-7288881 I2D: score=2 STRING: ENSP00000344818
    About this table

    Gene Ontology (GO): 5/15 biological process terms (GO ID links to tree view) (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006511ubiquitin-dependent protein catabolic process IEA--
    GO:0006917induction of apoptosis IDA--
    GO:0007049cell cycle IEA--
    GO:0007346regulation of mitotic cell cycle IMP17495026
    GO:0016055Wnt receptor signaling pathway IEA--


    CYLD for ontologies           About GeneDecksing



    Drugs & Compounds
    for CYLD gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    CYLD for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    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 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)

    Search CenterWatch for drugs/clinical trials and news about CYLD 

    Transcripts
    for CYLD gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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
    Products:             		 OriGene 3'-UTR Clone (see all 3): CYLD
    Browse OriGene MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CYLD
    8/107 QIAGEN miScript miRNA 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
    Products:             		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CYLD (see all 7)
    OriGene shRNA RFP: CYLD
    Browse OriGene siRNA
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CYLD
    Clone
    Products:             		 OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CYLD (see all 8)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CYLD (see all 4)
    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)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CYLD
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CYLD 
    Primer
    Products:            		 OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for CYLD
    Browse OriGene validated miRNA SYBR primer pairs
    SABiosciences RT2 qPCR Primer Assay in human, mouse, rat CYLD
      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat CYLD
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat CYLD

    Additional cDNA 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 

    24/263 AceView cDNA sequences (see all 263):

    CA447364 CA312385 CA946813 AA761514 AW137063 CA445743 AA150209 AA346448 
    BM719060 AW468254 CF528626 CD723460 AI342250 CD742887 CD673004 BX378855 
    AA731089 BM699035 CD678606 BQ006009 CA447022 AL134294 AW272888 AK024348 

    GeneLoc Exon Structure

    5/8 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

    Expression
    for CYLD gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    CYLD expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: AGAATCTCTT

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    CYLD expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    4 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Gut TubeHindgutHindgut Endoderm CellsEndoderm
    Gut TubeMidgutMidgut Endoderm CellsEndoderm
    Gut TubeHindgutGut Tube
    Gut TubeMidgutGut Tube
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See CYLD Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for CYLD

    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

        SABiosciences Expression via Pathway-Focused 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

    Primer
    Products:    		 OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for CYLD
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    In Situ
    Assay Products:     
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYLD

    Orthologs
    for CYLD gene

    (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)
    About This Section
    This gene was present in the common ancestor of animals.

    Orthologs for CYLD gene from 7/19 species (see all 19)    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_001128169.11  NP_001121641.11 
     886970285 
    chicken
    (Gallus gallus)    		 Aves CYLD1 cylindromatosis (turban tumor syndrome) 81.57(n)
    87.93(a)    		   415725  XM_414091.3  XP_414091.2 
    lizard
    (Anolis carolinensis)    		 Reptilia CYLD6
    		 --
    		 81(a)
    		 1 ↔ 1
    		 GL343227.1(1170436-1189173)
    African clawed frog
    (Xenopus laevis)    		 Amphibia Xl.114462 Xenopus laevis transcribed sequence with weak similarity to protein refNP_056062.1 (H.sapiens) cylindromatosis (turban tumor syndrome); cylindromatosis 1, turban tumor syndrome [Homo sapiens] less 75.46(n)    AW640982.1 
    zebrafish
    (Danio rerio)    		 Actinopterygii Dr.183432 Transcribed sequence with weak similarity to protein refNP_056062.1 (H.sapiens) cylindromatosis (turban tumor syndrome); cylindromatosis 1, turban tumor syndrome [Homo sapiens] less 77.02(n)    BQ260477.1 
    fruit fly
    (Drosophila melanogaster)    		 Insecta CG56033
    CYLD1    		 transcription factor3
    cylindromatosis1    		 45(a)3
    54.29(n)1
    48.28(a)1    		   343801  NM_164911.11  NP_723556.11 
    worm
    (Caenorhabditis elegans)    		 Secernentea F40F12.5a3 Ubiquitin carboxyl-terminal hydrolases
    family 2 less    		 35(a)   III(9970710-9982367)   --


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

    Paralogs
    for CYLD gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    		  --

    Genomic Variants
    for CYLD gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/893 NCBI SNPs in CYLD are shown (see all 893)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 16 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs80607651,2
    		C,--36660981(+) attggC/Ttcatg 2 -- us2k10--------
    rs604552261,2
    		C,--36661016(+) GCTGAC/TGCAGG 3 -- us2k11Minor allele frequency- T:0.50WA 2
    rs753324411,2
    		C,--36661443(+) CAAATA/CTCTCT 3 -- us2k10--------
    rs773687031,2
    		C,--36661587(+) TGAGAA/GCGGTG 3 -- us2k10--------
    rs169487891,2
    		C,F,H,--36661651(+) CTACAG/ACAGTG 3 -- us2k113Minor allele frequency- A:0.02NA NS EA CSA WA 1066
    rs783679501,2
    		F,--36661894(+) TGTGTC/TATGAT 3 -- us2k11Minor allele frequency- T:0.04WA 118
    rs750873171,2
    		C,--36662357(+) TGCCAA/CAATCC 3 -- us2k10--------
    rs769836321,2
    		C,--36663859(+) CGGGGG/TTCTGG 3 -- int10--------
    rs71998421,2
    		C,--36664423(+) CACCCC/TCTCAC 3 -- int12Minor allele frequency- T:0.04CSA WA 119
    rs13626981,2
    		C,F,A,H,--36664528(-) TTCCAG/ACAAAT 3 -- int124Minor allele frequency- A:0.17NA EA MN NS WA CSA 2279

    HapMap Linkage Disequilibrium report for CYLD (50775961 - 50835846 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for CYLD: --
    Human Gene Mutation Database (HGMD): CYLD

    2 SABiosciences Cancer Mutation PCR Assays for CYLD:
    Cosmic IdAA Change
    21988p.R758*
    21989p.Q905*
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing CYLD
    DNA2.0 Custom Variant and Variant Library Synthesis for CYLD

    Disorders / Diseases
    for CYLD gene

    (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.)
    About This Section
    CYLD for disorders           About GeneDecksing

    OMIM gene information: 605018   
    OMIM disorders: 132700  605041  601606  
    UniProtKB/Swiss-Prot: CYLD_HUMAN, Q9NQC7
  • Defects in CYLD are the cause of familial cylindromatosis (FCYL) [MIM:132700]; also known as Ancell-Spiegler
    • cylindromas or turban tumor syndrome or dermal eccrine cylindromatosis. CYLD is an autosomal dominant and highly tumor
    type-specific disorder. The tumors (known as cylindromas because of their characteristic microscopic architecture) are
    believed to arise from or recapitulate the appearance of the eccrine or apocrine cells of the skin that secrete sweat
    and scent respectively. Cylindromas arise predominantly in hairy parts of the body with approximately 90% on the head
    and neck. The development of a confluent mass which may ulcerate or become infected has led to the designation 'turban
    tumor syndrome'. The skin tumors show differentiation in the direction of hair structures, hence the synonym
    trichoepithelioma
  • Defects in CYLD are the cause of multiple familial trichoepithelioma type 1 (MFT1) [MIM:601606]; also known as
    • epithelioma adenoides cysticum of Brooke (EAC) or hereditary multiple benign cystic epithelioma or Brooke-Fordyce
    trichoepitheliomas. MFT1 is an 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
  • Defects in CYLD are the cause of Brooke-Spiegler syndrome (BRSS) [MIM:605041]. BRSS is 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

    20/21 diseases for CYLD (see all 21):    About MalaCards
    brooke-spiegler syndrome    cylindromatosis    multiple familial trichoepithelioma    trichoepithelioma
    regular astigmatism    familial cylindromatosis    haemophilus influenzae    spiradenoma
    basal cell carcinoma    hodgkin's lymphoma    multiple myeloma    influenza
    skin cancer    myeloma    hepatocellular carcinoma    t-cell leukemia
    carcinoma    nephropathy    pneumonia    leukemia

    3 diseases from the University of Copenhagen DISEASES database for CYLD:
    Brooke-Spiegler syndrome     Spiradenoma     Adenoid cystic carcinoma

    6 Novoseek 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

    Publications
    for CYLD gene

    (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)
    About This Section

    PubMed articles for CYLD gene, integrated from 9 sources (see all 138):
    (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 i nactivating HDAC6 and increasing the levels of acetylated tubulin. (PubMed id 19893491)1, 2, 9 WickstrAPm S.A....Massoumi R. (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. (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. (2008)
    4. Loss of the tumor suppressor CYLD enhances Wnt/beta-c atenin signaling through K63-linked ubiquitination of Dvl. (PubMed id 20227366)1, 2, 9 Tauriello D.V....Maurice M.M. (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. (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. (2003)
    7. Identification of the familial cylindromatosis tumor suppressor gene. (PubMed id 10835629)1, 2, 9 Bignell G.R.... Stratton M.R. (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. (2005)
    9. The tumor suppressor CYLD regulates microtubule dynamics and plays a role in cell migration. (PubMed id 18222923)1, 2 Gao J....Zhou J. (2008)
    10. The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module. (PubMed id 18313383)1, 2 Komander D....Barford D. (2008)

    External Searches for CYLD gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing CYLD gene

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

    Other Databases showing CYLD gene

    (According to HUGE)
    About This Section
    HUGE: KIAA0849

    Specialized Databases showing CYLD gene

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

    Intellectual Property
    for CYLD gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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



    Products
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    About This Section

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