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Q5RED8

- CYLD_PONAB

UniProt

Q5RED8 - CYLD_PONAB

Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

CYLD

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 64 (01 Oct 2014)
      Sequence version 1 (21 Dec 2004)
      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 By similarity. 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).

    Sites

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

    GO - Molecular functioni

    1. ubiquitin-specific protease activity Source: UniProtKB
    2. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
    2. negative regulation of NF-kappaB import into nucleus Source: UniProtKB
    3. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    4. protein K63-linked deubiquitination Source: UniProtKB
    5. ubiquitin-dependent protein catabolic process Source: InterPro
    6. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Ubl conjugation pathway, Wnt signaling pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    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
    OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
    Taxonomic identifieri9601 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
    ProteomesiUP000001595: Unplaced

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. microtubule Source: UniProtKB-KW
    3. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    4. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Microtubule

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 956956Ubiquitin carboxyl-terminal hydrolase CYLDPRO_0000326148Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei418 – 4181PhosphoserineBy similarity

    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 By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    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

    Structurei

    3D structure databases

    ProteinModelPortaliQ5RED8.
    SMRiQ5RED8. Positions 125-206, 228-307, 457-550, 583-956.
    ModBaseiSearch...
    MobiDBiSearch...

    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 – 684215Interaction 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

    HOGENOMiHOG000006796.
    HOVERGENiHBG051281.
    InParanoidiQ5RED8.
    KOiK08601.

    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]

    Sequencei

    Sequence statusi: Complete.

    Q5RED8-1 [UniParc]FASTAAdd to Basket

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    MSSGLWSQDK VTSPYWEERV FYLLLQECSV TDKQTQKLLK VPKGSIGQYI    50
    QDRSVGHSRI PSAKGKKNRI 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 STENRFHSLP 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):107,302
    Last modified:December 21, 2004 - v1
    Checksum:iADDCE3C7241D828B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CR857591 mRNA. Translation: CAH89869.1.
    RefSeqiNP_001124871.1. NM_001131399.1.
    UniGeneiPab.1922.

    Genome annotation databases

    GeneIDi100171734.
    KEGGipon:100171734.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CR857591 mRNA. Translation: CAH89869.1 .
    RefSeqi NP_001124871.1. NM_001131399.1.
    UniGenei Pab.1922.

    3D structure databases

    ProteinModelPortali Q5RED8.
    SMRi Q5RED8. Positions 125-206, 228-307, 457-550, 583-956.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi C67.001.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100171734.
    KEGGi pon:100171734.

    Organism-specific databases

    CTDi 1540.

    Phylogenomic databases

    HOGENOMi HOG000006796.
    HOVERGENi HBG051281.
    InParanoidi Q5RED8.
    KOi K08601.

    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. The German cDNA consortium
      Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain cortex.

    Entry informationi

    Entry nameiCYLD_PONAB
    AccessioniPrimary (citable) accession number: Q5RED8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 18, 2008
    Last sequence update: December 21, 2004
    Last modified: October 1, 2014
    This is version 64 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Peptidase families
      Classification of peptidase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3