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Q5RED8 (CYLD_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 63. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CYLD
Synonyms:CYLD1
OrganismPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo

Protein attributes

Sequence length956 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 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 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).

Subunit structure

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 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.

Post-translational modification

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.

Sequence similarities

Belongs to the peptidase C19 family.

Contains 3 CAP-Gly domains.

Contains 1 USP domain.

Ontologies

Keywords
   Biological processUbl conjugation pathway
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Microtubule
   DomainRepeat
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Protease
Thiol protease
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of NF-kappaB import into nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

protein K63-linked deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionubiquitin-specific protease activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 956956Ubiquitin carboxyl-terminal hydrolase CYLD
PRO_0000326148

Regions

Domain153 – 19846CAP-Gly 1
Domain253 – 28634CAP-Gly 2
Domain492 – 53544CAP-Gly 3
Domain592 – 950359USP
Region106 – 593488Interaction with TRIP
Region394 – 46976Interaction with TRAF2
Region470 – 684215Interaction with IKBKG/NEMO

Sites

Active site6011Nucleophile By similarity
Active site8711Proton acceptor By similarity
Metal binding7881Zinc 1 By similarity
Metal binding7911Zinc 1 By similarity
Metal binding7991Zinc 2 By similarity
Metal binding8021Zinc 2 By similarity
Metal binding8171Zinc 1 By similarity
Metal binding8201Zinc 1 By similarity
Metal binding8251Zinc 2 By similarity
Metal binding8331Zinc 2 By similarity

Amino acid modifications

Modified residue4181Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5RED8 [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: ADDCE3C7241D828B

FASTA956107,302
        10         20         30         40         50         60 
MSSGLWSQDK VTSPYWEERV FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRI 

        70         80         90        100        110        120 
PSAKGKKNRI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERF SLFKNRNRLS 

       130        140        150        160        170        180 
KGLQIDVGCP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 

       190        200        210        220        230        240 
YQGKQLFQCD EDCGVFVALD KLELIEDDDT ALESDYAGPG DTMQVELPPL EINSRVSLKV 

       250        260        270        280        290        300 
GETIESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAC VESTILLHIN 

       310        320        330        340        350        360 
DIIPALSESV TQERRPPKLA FMSRGVGDKG SSSHNKPKAT GSTSDPGNRN RSELFYTLNG 

       370        380        390        400        410        420 
SSVDSQPQSK SKNTWYIDEV AEDPAKSLTE ISTDFDRSSP PLQPPPVNSL STENRFHSLP 

       430        440        450        460        470        480 
FSLTKMPNTN GSIGHSPLSL SAQSVMEELN TAPVQESPPL AMPPGNSHGL EVGSLAEVKE 

       490        500        510        520        530        540 
NPPFYGVIRW IGQPPGLNEV LAGLELEDEC AGCTDGTFRG TRYFTCALKK ALFVKLKSCR 

       550        560        570        580        590        600 
PDSRFASLQP VSNQIERCNS LAFGGYLSEV VEENTPPKME KEGLEIMIGK KKGIQGHYNS 

       610        620        630        640        650        660 
CYLDSTLFCL FAFSSVLDTV LLRPKEKNDV EYYSETQELL RTEIVNPLRI YGYVCATKIM 

       670        680        690        700        710        720 
KLRKILEKVE AASGFTSEEK DPEEFLNILF HHILRVEPLL KIRSAGQKVQ DCYFYQIFME 

       730        740        750        760        770        780 
KNEKVGVPTI QQLLEWSFIN SNLKFAEAPS CLIIQMPRFG KDFKLFKKIF PSLELNITDL 

       790        800        810        820        830        840 
LEDTPRQCRI CGGLAMYECR ECYDDPDISA GKIKQFCKTC NTQVHLHPKR LNHKYNPVSL 

       850        860        870        880        890        900 
PKDLPDWDWR HGCIPCQNME LFAVLCIETS HYVAFVKYGK DDSAWLFFDS MADRDGGQNG 

       910        920        930        940        950 
FNIPQVTPCP EVGEYLKMSL EDLHSLDSRR IQGCARRLLC DAYMCMYQSP TMSLYK 

« Hide

References

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CR857591 mRNA. Translation: CAH89869.1.
RefSeqNP_001124871.1. NM_001131399.1.
UniGenePab.1922.

3D structure databases

ProteinModelPortalQ5RED8.
SMRQ5RED8. Positions 125-206, 228-307, 457-550, 583-956.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSC67.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100171734.
KEGGpon:100171734.

Organism-specific databases

CTD1540.

Phylogenomic databases

HOGENOMHOG000006796.
HOVERGENHBG051281.
InParanoidQ5RED8.
KOK08601.

Family and domain databases

Gene3D2.30.30.190. 3 hits.
InterProIPR000938. CAP-Gly_domain.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF01302. CAP_GLY. 3 hits.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTSM01052. CAP_GLY. 3 hits.
[Graphical view]
SUPFAMSSF74924. SSF74924. 3 hits.
PROSITEPS00845. CAP_GLY_1. 1 hit.
PS50245. CAP_GLY_2. 2 hits.
PS00972. USP_1. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameCYLD_PONAB
AccessionPrimary (citable) accession number: Q5RED8
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries