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Q5RED8

- CYLD_PONAB

UniProt

Q5RED8 - CYLD_PONAB

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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene
CYLD, CYLD1
Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

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.

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 – 6011Nucleophile By similarity
Metal bindingi788 – 7881Zinc 1 By similarity
Metal bindingi791 – 7911Zinc 1 By similarity
Metal bindingi799 – 7991Zinc 2 By similarity
Metal bindingi802 – 8021Zinc 2 By similarity
Metal bindingi817 – 8171Zinc 1 By similarity
Metal bindingi820 – 8201Zinc 1 By similarity
Metal bindingi825 – 8251Zinc 2 By similarity
Metal bindingi833 – 8331Zinc 2 By similarity
Active sitei871 – 8711Proton acceptor By similarity

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
Complete GO annotation...

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; Peripheral membrane protein; Cytoplasmic side By similarity
Note: Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase 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
Complete GO annotation...

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 – 4181Phosphoserine By 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.

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.

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini153 – 19846CAP-Gly 1Add
BLAST
Domaini253 – 28634CAP-Gly 2Add
BLAST
Domaini492 – 53544CAP-Gly 3Add
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.
Contains 3 CAP-Gly domains.
Contains 1 USP domain.

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: April 16, 2014
This is version 63 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

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