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Q9NQC7

- CYLD_HUMAN

UniProt

Q9NQC7 - CYLD_HUMAN

Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

CYLD

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 Oct 2000)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

    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).1 Publication

    Enzyme regulationi

    Inhibited by phosphorylation at serine residues.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei601 – 6011Nucleophile1 PublicationPROSITE-ProRule annotation
    Metal bindingi788 – 7881Zinc 1
    Metal bindingi791 – 7911Zinc 1
    Metal bindingi799 – 7991Zinc 2
    Metal bindingi802 – 8021Zinc 2
    Metal bindingi817 – 8171Zinc 1
    Metal bindingi820 – 8201Zinc 1
    Metal bindingi825 – 8251Zinc 2
    Metal bindingi833 – 8331Zinc 2
    Active sitei871 – 8711Proton acceptor1 Publication

    GO - Molecular functioni

    1. Lys63-specific deubiquitinase activity Source: UniProtKB
    2. proline-rich region binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein kinase binding Source: UniProtKB
    5. ubiquitin-specific protease activity Source: UniProtKB
    6. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. innate immune response Source: Reactome
    3. necroptotic process Source: RefGenome
    4. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
    5. negative regulation of NF-kappaB import into nucleus Source: UniProtKB
    6. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    7. negative regulation of type I interferon production Source: Reactome
    8. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
    9. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
    10. positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
    11. protein K63-linked deubiquitination Source: UniProtKB
    12. regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    13. regulation of microtubule cytoskeleton organization Source: UniProtKB
    14. regulation of mitotic cell cycle Source: UniProtKB
    15. ubiquitin-dependent protein catabolic process Source: InterPro
    16. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Cell cycle, Ubl conjugation pathway, Wnt signaling pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_75776. NOD1/2 Signaling Pathway.

    Protein family/group databases

    MEROPSiC67.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase CYLD (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme CYLD
    Ubiquitin thioesterase CYLD
    Ubiquitin-specific-processing protease CYLD
    Gene namesi
    Name:CYLD
    Synonyms:CYLD1, KIAA0849
    ORF Names:HSPC057
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:2584. CYLD.

    Subcellular locationi

    Cytoplasm. Cytoplasmperinuclear region. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side
    Note: Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase.

    GO - Cellular componenti

    1. centrosome Source: HPA
    2. cytosol Source: UniProtKB
    3. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
    4. microtubule Source: UniProtKB-KW
    5. nucleus Source: HPA
    6. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Microtubule

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti747 – 7471E → G in MFT1 and BRSS. 1 Publication
    VAR_045967
    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.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti747 – 7471E → G in MFT1 and BRSS. 1 Publication
    VAR_045967

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi418 – 4181S → A: Reduced phosphorylation; when associated with A-422; A-432 and A-436. Loss of phosphorylation; when associated with A-422; A-432; A-436; A-439; A-441 and A-444. 1 Publication
    Mutagenesisi418 – 4181S → E: Abolishes deubiquitination of TRAF2; when associated with E-422; E-432; E-436; E-439; E-441 and E-444. 1 Publication
    Mutagenesisi422 – 4221S → A: Reduced phosphorylation; when associated with A-418; A-432 and A-436. Loss of phosphorylation; when associated with A-418; A-432; A-436; A-439; A-441 and A-444. 1 Publication
    Mutagenesisi422 – 4221S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-432; E-436; E-439; E-441 and E-444. 1 Publication
    Mutagenesisi432 – 4321S → A: Slightly reduced phosphorylation; when associated with A-436. Reduced phosphorylation; when associated with A-418; A-422 and A-436. Loss of phosphorylation; when associated with A-418; A-422; A-436; A-439; A-441 and A-444. 1 Publication
    Mutagenesisi432 – 4321S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-436; E-439; E-441 and E-444. 1 Publication
    Mutagenesisi436 – 4361S → A: Slightly reduced phosphorylation; when associated with A-432. Reduced phosphorylation; when associated with A-418; A-422 and A-432. Loss of phosphorylation; when associated with A-418; A-422; A-432; A-439; A-441 and A-444. 1 Publication
    Mutagenesisi436 – 4361S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-439; E-441 and E-444. 1 Publication
    Mutagenesisi439 – 4391S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-441 and A-444. 1 Publication
    Mutagenesisi439 – 4391S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-441 and E-444. 1 Publication
    Mutagenesisi441 – 4411S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-444. 1 Publication
    Mutagenesisi441 – 4411S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-444. 1 Publication
    Mutagenesisi444 – 4441S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-441. 1 Publication
    Mutagenesisi444 – 4441S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-441. 1 Publication
    Mutagenesisi457 – 4571S → A: Abolishes binding to TRAF2. 1 Publication
    Mutagenesisi601 – 6011C → A or S: Loss of deubiquitinating activity. 4 Publications
    Mutagenesisi871 – 8711H → N: Loss of deubiquitinating activity. 1 Publication

    Keywords - Diseasei

    Disease mutation, Tumor suppressor

    Organism-specific databases

    MIMi132700. phenotype.
    601606. phenotype.
    605041. phenotype.
    Orphaneti211. Familial cylindromatosis.
    867. Familial multiple trichoepithelioma.
    PharmGKBiPA27084.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 956956Ubiquitin carboxyl-terminal hydrolase CYLDPRO_0000080698Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei418 – 4181Phosphoserine1 Publication

    Post-translational modificationi

    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-B.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9NQC7.
    PaxDbiQ9NQC7.
    PRIDEiQ9NQC7.

    PTM databases

    PhosphoSiteiQ9NQC7.

    Expressioni

    Tissue specificityi

    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.1 Publication

    Gene expression databases

    ArrayExpressiQ9NQC7.
    BgeeiQ9NQC7.
    CleanExiHS_CYLD.
    GenevestigatoriQ9NQC7.

    Organism-specific databases

    HPAiCAB011713.
    HPA050095.

    Interactioni

    Subunit structurei

    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.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DDX58O957862EBI-2117940,EBI-995350
    HDAC6Q9UBN74EBI-2117940,EBI-301697
    ITCHQ96J023EBI-2117940,EBI-1564678
    ITCHQ96J02-22EBI-2117940,EBI-6672198
    TUBA1AQ71U366EBI-2117940,EBI-302552

    Protein-protein interaction databases

    BioGridi107920. 40 interactions.
    IntActiQ9NQC7. 23 interactions.
    MINTiMINT-6804518.
    STRINGi9606.ENSP00000308928.

    Structurei

    Secondary structure

    1
    956
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi130 – 1345
    Beta strandi136 – 1394
    Beta strandi141 – 1499
    Beta strandi154 – 1574
    Beta strandi163 – 1675
    Beta strandi169 – 1713
    Turni191 – 1933
    Beta strandi194 – 1974
    Helixi199 – 2013
    Beta strandi202 – 2043
    Beta strandi235 – 2406
    Beta strandi243 – 25311
    Turni259 – 2613
    Beta strandi264 – 2729
    Beta strandi278 – 2803
    Beta strandi283 – 2853
    Beta strandi293 – 2986
    Helixi299 – 3013
    Beta strandi302 – 3043
    Turni463 – 4653
    Beta strandi466 – 4683
    Beta strandi474 – 4785
    Beta strandi480 – 4823
    Beta strandi486 – 4927
    Beta strandi495 – 4973
    Beta strandi501 – 5088
    Beta strandi514 – 5185
    Beta strandi531 – 5355
    Helixi536 – 5383
    Beta strandi539 – 5413
    Helixi584 – 5863
    Beta strandi588 – 5914
    Helixi601 – 61111
    Beta strandi612 – 6143
    Helixi615 – 6173
    Helixi618 – 6225
    Helixi633 – 64210
    Helixi645 – 6506
    Beta strandi652 – 6543
    Helixi656 – 66914
    Helixi682 – 6909
    Turni691 – 6944
    Beta strandi699 – 7046
    Beta strandi710 – 7134
    Helixi730 – 74112
    Beta strandi743 – 7475
    Beta strandi750 – 7556
    Beta strandi760 – 7645
    Beta strandi773 – 7753
    Helixi778 – 7803
    Beta strandi781 – 7844
    Turni789 – 7913
    Helixi800 – 8023
    Turni806 – 8116
    Helixi818 – 8247
    Helixi828 – 8303
    Beta strandi859 – 86810
    Beta strandi871 – 8777
    Beta strandi879 – 8813
    Beta strandi885 – 8895
    Beta strandi905 – 9084
    Helixi911 – 9144
    Helixi920 – 9256
    Helixi928 – 9303
    Helixi935 – 9406
    Beta strandi944 – 9485
    Helixi950 – 9523

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IXDNMR-A460-550[»]
    1WHLNMR-A125-206[»]
    1WHMNMR-A228-304[»]
    2VHFX-ray2.80A/B583-956[»]
    ProteinModelPortaliQ9NQC7.
    SMRiQ9NQC7. Positions 125-206, 228-307, 457-550, 583-956.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NQC7.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini153 – 19846CAP-Gly 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini253 – 28634CAP-Gly 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini492 – 53544CAP-Gly 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini592 – 950359USPAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni106 – 593488Interaction with TRIPAdd
    BLAST
    Regioni394 – 46976Interaction with TRAF2Add
    BLAST
    Regioni470 – 55485Interaction with IKBKG/NEMOAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C19 family.Curated
    Contains 3 CAP-Gly domains.PROSITE-ProRule annotation
    Contains 1 USP domain.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG313578.
    HOGENOMiHOG000006796.
    HOVERGENiHBG051281.
    InParanoidiQ9NQC7.
    KOiK08601.
    OrthoDBiEOG72ZCDM.
    PhylomeDBiQ9NQC7.
    TreeFamiTF318734.

    Family and domain databases

    Gene3Di2.30.30.190. 3 hits.
    InterProiIPR000938. CAP-Gly_domain.
    IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    [Graphical view]
    PfamiPF01302. CAP_GLY. 3 hits.
    PF00443. UCH. 1 hit.
    [Graphical view]
    SMARTiSM01052. CAP_GLY. 3 hits.
    [Graphical view]
    SUPFAMiSSF74924. SSF74924. 3 hits.
    PROSITEiPS00845. CAP_GLY_1. 1 hit.
    PS50245. CAP_GLY_2. 2 hits.
    PS00972. USP_1. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9NQC7-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI    50
    QDRSVGHSRI PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL 100
    LAITNCEERF SLFKNRNRLS KGLQIDVGCP VKVQLRSGEE KFPGVVRFRG 150
    PLLAERTVSG IFFGVELLEE GRGQGFTDGV YQGKQLFQCD EDCGVFVALD 200
    KLELIEDDDT ALESDYAGPG DTMQVELPPL EINSRVSLKV GETIESGTVI 250
    FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAC VESTILLHIN 300
    DIIPALSESV TQERRPPKLA FMSRGVGDKG SSSHNKPKAT GSTSDPGNRN 350
    RSELFYTLNG SSVDSQPQSK SKNTWYIDEV AEDPAKSLTE ISTDFDRSSP 400
    PLQPPPVNSL TTENRFHSLP FSLTKMPNTN GSIGHSPLSL SAQSVMEELN 450
    TAPVQESPPL AMPPGNSHGL EVGSLAEVKE NPPFYGVIRW IGQPPGLNEV 500
    LAGLELEDEC AGCTDGTFRG TRYFTCALKK ALFVKLKSCR PDSRFASLQP 550
    VSNQIERCNS LAFGGYLSEV VEENTPPKME KEGLEIMIGK KKGIQGHYNS 600
    CYLDSTLFCL FAFSSVLDTV LLRPKEKNDV EYYSETQELL RTEIVNPLRI 650
    YGYVCATKIM KLRKILEKVE AASGFTSEEK DPEEFLNILF HHILRVEPLL 700
    KIRSAGQKVQ DCYFYQIFME KNEKVGVPTI QQLLEWSFIN SNLKFAEAPS 750
    CLIIQMPRFG KDFKLFKKIF PSLELNITDL LEDTPRQCRI CGGLAMYECR 800
    ECYDDPDISA GKIKQFCKTC NTQVHLHPKR LNHKYNPVSL PKDLPDWDWR 850
    HGCIPCQNME LFAVLCIETS HYVAFVKYGK DDSAWLFFDS MADRDGGQNG 900
    FNIPQVTPCP EVGEYLKMSL EDLHSLDSRR IQGCARRLLC DAYMCMYQSP 950
    TMSLYK 956
    Length:956
    Mass (Da):107,316
    Last modified:October 1, 2000 - v1
    Checksum:i01831F9A83424631
    GO
    Isoform 2 (identifier: Q9NQC7-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         305-307: Missing.

    Show »
    Length:953
    Mass (Da):107,044
    Checksum:i0CCB3D21E2FF8851
    GO

    Sequence cautioni

    The sequence AAF29029.1 differs from that shown. Reason: Frameshift at positions 776, 808 and 932.
    The sequence BAA74872.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti747 – 7471E → G in MFT1 and BRSS. 1 Publication
    VAR_045967

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei305 – 3073Missing in isoform 2. 2 PublicationsVSP_011277

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ250014 mRNA. Translation: CAB93533.1.
    AB020656 mRNA. Translation: BAA74872.2. Different initiation.
    BC012342 mRNA. Translation: AAH12342.1.
    AF161542 mRNA. Translation: AAF29029.1. Frameshift.
    CCDSiCCDS42164.1. [Q9NQC7-2]
    CCDS45482.1. [Q9NQC7-1]
    RefSeqiNP_001035814.1. NM_001042355.1. [Q9NQC7-2]
    NP_001035877.1. NM_001042412.1. [Q9NQC7-2]
    NP_056062.1. NM_015247.2. [Q9NQC7-1]
    XP_005255869.1. XM_005255812.2. [Q9NQC7-2]
    XP_006721211.1. XM_006721148.1. [Q9NQC7-2]
    XP_006721212.1. XM_006721149.1. [Q9NQC7-2]
    XP_006721213.1. XM_006721150.1. [Q9NQC7-2]
    XP_006721214.1. XM_006721151.1. [Q9NQC7-2]
    UniGeneiHs.578973.

    Genome annotation databases

    GeneIDi1540.
    KEGGihsa:1540.
    UCSCiuc002egp.1. human. [Q9NQC7-1]
    uc002egq.1. human. [Q9NQC7-2]

    Polymorphism databases

    DMDMi51316104.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ250014 mRNA. Translation: CAB93533.1 .
    AB020656 mRNA. Translation: BAA74872.2 . Different initiation.
    BC012342 mRNA. Translation: AAH12342.1 .
    AF161542 mRNA. Translation: AAF29029.1 . Frameshift.
    CCDSi CCDS42164.1. [Q9NQC7-2 ]
    CCDS45482.1. [Q9NQC7-1 ]
    RefSeqi NP_001035814.1. NM_001042355.1. [Q9NQC7-2 ]
    NP_001035877.1. NM_001042412.1. [Q9NQC7-2 ]
    NP_056062.1. NM_015247.2. [Q9NQC7-1 ]
    XP_005255869.1. XM_005255812.2. [Q9NQC7-2 ]
    XP_006721211.1. XM_006721148.1. [Q9NQC7-2 ]
    XP_006721212.1. XM_006721149.1. [Q9NQC7-2 ]
    XP_006721213.1. XM_006721150.1. [Q9NQC7-2 ]
    XP_006721214.1. XM_006721151.1. [Q9NQC7-2 ]
    UniGenei Hs.578973.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IXD NMR - A 460-550 [» ]
    1WHL NMR - A 125-206 [» ]
    1WHM NMR - A 228-304 [» ]
    2VHF X-ray 2.80 A/B 583-956 [» ]
    ProteinModelPortali Q9NQC7.
    SMRi Q9NQC7. Positions 125-206, 228-307, 457-550, 583-956.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107920. 40 interactions.
    IntActi Q9NQC7. 23 interactions.
    MINTi MINT-6804518.
    STRINGi 9606.ENSP00000308928.

    Protein family/group databases

    MEROPSi C67.001.

    PTM databases

    PhosphoSitei Q9NQC7.

    Polymorphism databases

    DMDMi 51316104.

    Proteomic databases

    MaxQBi Q9NQC7.
    PaxDbi Q9NQC7.
    PRIDEi Q9NQC7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 1540.
    KEGGi hsa:1540.
    UCSCi uc002egp.1. human. [Q9NQC7-1 ]
    uc002egq.1. human. [Q9NQC7-2 ]

    Organism-specific databases

    CTDi 1540.
    GeneCardsi GC16P050775.
    HGNCi HGNC:2584. CYLD.
    HPAi CAB011713.
    HPA050095.
    MIMi 132700. phenotype.
    601606. phenotype.
    605018. gene.
    605041. phenotype.
    neXtProti NX_Q9NQC7.
    Orphaneti 211. Familial cylindromatosis.
    867. Familial multiple trichoepithelioma.
    PharmGKBi PA27084.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG313578.
    HOGENOMi HOG000006796.
    HOVERGENi HBG051281.
    InParanoidi Q9NQC7.
    KOi K08601.
    OrthoDBi EOG72ZCDM.
    PhylomeDBi Q9NQC7.
    TreeFami TF318734.

    Enzyme and pathway databases

    Reactomei REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_75776. NOD1/2 Signaling Pathway.

    Miscellaneous databases

    EvolutionaryTracei Q9NQC7.
    GeneWikii CYLD_(gene).
    GenomeRNAii 1540.
    NextBioi 6377.
    PROi Q9NQC7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9NQC7.
    Bgeei Q9NQC7.
    CleanExi HS_CYLD.
    Genevestigatori Q9NQC7.

    Family and domain databases

    Gene3Di 2.30.30.190. 3 hits.
    InterProi IPR000938. CAP-Gly_domain.
    IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    [Graphical view ]
    Pfami PF01302. CAP_GLY. 3 hits.
    PF00443. UCH. 1 hit.
    [Graphical view ]
    SMARTi SM01052. CAP_GLY. 3 hits.
    [Graphical view ]
    SUPFAMi SSF74924. SSF74924. 3 hits.
    PROSITEi PS00845. CAP_GLY_1. 1 hit.
    PS50245. CAP_GLY_2. 2 hits.
    PS00972. USP_1. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INVOLVEMENT IN FAMILIAL CYLINDROMATOSIS.
    2. "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Brain.
    3. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
      Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
      DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Uterus.
    5. "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
      Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X.
      , Gu J., Chen S.-J., Chen Z.
      Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 397-956.
      Tissue: Umbilical cord blood.
    6. "CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members."
      Trompouki E., Hatzivassiliou E., Tsichritzis T., Farmer H., Ashworth A., Mosialos G.
      Nature 424:793-796(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IKBKG/NEMO, MUTAGENESIS OF CYS-601.
    7. "Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB."
      Brummelkamp T.R., Nijman S.M.B., Dirac A.M.G., Bernards R.
      Nature 424:797-801(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IKBKG/NEMO, MUTAGENESIS OF CYS-601.
    8. "The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination."
      Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D., Courtois G.
      Nature 424:801-805(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IKBKG/NEMO AND TRAF2, MUTAGENESIS OF SER-457 AND HIS-871.
    9. "The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor kappaB activation by tumor necrosis factor."
      Regamey A., Hohl D., Liu J.W., Roger T., Kogerman P., Toftgaard R., Huber M.
      J. Exp. Med. 198:1959-1964(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TRIP.
    10. "Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation."
      Reiley W., Zhang M., Wu X., Granger E., Sun S.C.
      Mol. Cell. Biol. 25:3886-3895(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TRAF2, ENZYME REGULATION, MUTAGENESIS OF SER-418; SER-422; SER-432; SER-436; SER-439; SER-441 AND SER-444, PHOSPHORYLATION AT SER-418.
    11. Cited for: FUNCTION, MUTAGENESIS OF CYS-601, INTERACTION WITH PLK1, SUBCELLULAR LOCATION.
    12. Cited for: FUNCTION, SUBUNIT, INTERACTION WITH DDX58; MAVS; TBK1 AND IKKE.
    13. "The tumor suppressor CYLD regulates microtubule dynamics and plays a role in cell migration."
      Gao J., Huo L., Sun X., Liu M., Li D., Dong J.T., Zhou J.
      J. Biol. Chem. 283:8802-8809(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    15. "CYLD regulates angiogenesis by mediating vascular endothelial cell migration."
      Gao J., Sun L., Huo L., Liu M., Li D., Zhou J.
      Blood 115:4130-4137(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    16. "CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin."
      Wickstrom S.A., Masoumi K.C., Khochbin S., Fassler R., Massoumi R.
      EMBO J. 29:131-144(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HDAC6; BCL3 AND MICROTUBULES, SUBCELLULAR LOCATION.
    17. "Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl."
      Tauriello D.V., Haegebarth A., Kuper I., Edelmann M.J., Henraat M., Canninga-van Dijk M.R., Kessler B.M., Clevers H., Maurice M.M.
      Mol. Cell 37:607-619(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH DVL1 AND DVL3.
    18. Cited for: STRUCTURE BY NMR OF 460-550, INTERACTION WITH IKBKG.
    19. "Solution structure of the 1st and 2nd CAP-Gly domains in human cylindromatosis tumor suppressor CYLD."
      RIKEN structural genomics initiative (RSGI)
      Submitted (NOV-2004) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 125-304.
    20. "Phenotype diversity in familial cylindromatosis: a frameshift mutation in the tumor suppressor gene CYLD underlies different tumors of skin appendages."
      Poblete Gutierrez P., Eggermann T., Hoeller D., Jugert F.K., Beermann T., Grussendorf-Conen E.-I., Zerres K., Merk H.F., Frank J.
      J. Invest. Dermatol. 119:527-531(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN FCYL, INVOLVEMENT IN BRSS.
    21. "Identification of a recurrent mutation in the CYLD gene in Brooke-Spiegler syndrome."
      Scheinfeld N., Hu G., Gill M., Austin C., Celebi J.T.
      Clin. Exp. Dermatol. 28:539-541(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN BRSS.
    22. "The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module."
      Komander D., Lord C.J., Scheel H., Swift S., Hofmann K., Ashworth A., Barford D.
      Mol. Cell 29:451-464(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 583-956 IN COMPLEX WITH ZINC IONS, FUNCTION, ACTIVE SITE, MUTAGENESIS OF CYS-601, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
    23. "A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome."
      Hu G., Oender M., Gill M., Aksakal B., Oeztas M., Guerer M.A., Celebi J.T.
      J. Invest. Dermatol. 121:732-734(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MFT1 GLY-747, VARIANT BRSS GLY-747.
    24. "Two novel CYLD gene mutations in Chinese families with trichoepithelioma and a literature review of 16 families with trichoepithelioma reported in China."
      Liang Y.H., Gao M., Sun L.D., Liu L.J., Cui Y., Yang S., Fan X., Wang J., Xiao F.L., Zhang X.J.
      Br. J. Dermatol. 153:1213-1215(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN MFT1.
    25. "Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation."
      Bowen S., Gill M., Lee D.A., Fisher G., Geronemus R.G., Vazquez M.E., Celebi J.T.
      J. Invest. Dermatol. 124:919-920(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN BRSS.
    26. "CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes."
      Young A.L., Kellermayer R., Szigeti R., Teszas A., Azmi S., Celebi J.T.
      Clin. Genet. 70:246-249(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN FCYL, INVOLVEMENT IN MFT1.

    Entry informationi

    Entry nameiCYLD_HUMAN
    AccessioniPrimary (citable) accession number: Q9NQC7
    Secondary accession number(s): O94934
    , Q7L3N6, Q96EH0, Q9NZX9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2004
    Last sequence update: October 1, 2000
    Last modified: October 1, 2014
    This is version 130 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

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