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Q66H62 (CYLD_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 80. 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length953 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

innate immune response

Inferred from Biological aspect of Ancestor. Source: RefGenome

necroptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

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

positive regulation of extrinsic apoptotic signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein K63-linked deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mitotic cell cycle

Inferred from Biological aspect of Ancestor. Source: RefGenome

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 thiolesterase activity

Inferred from electronic annotation. Source: InterPro

ubiquitin-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 – 953953Ubiquitin carboxyl-terminal hydrolase CYLD
PRO_0000326149

Regions

Domain153 – 19846CAP-Gly 1
Domain253 – 28634CAP-Gly 2
Domain489 – 53244CAP-Gly 3
Domain589 – 947359USP
Region106 – 590485Interaction with TRIP By similarity
Region391 – 46676Interaction with TRAF2 By similarity
Region467 – 681215Interaction with IKBKG/NEMO By similarity

Sites

Active site5981Nucleophile By similarity
Active site8681Proton acceptor By similarity
Metal binding7851Zinc 1 By similarity
Metal binding7881Zinc 1 By similarity
Metal binding7961Zinc 2 By similarity
Metal binding7991Zinc 2 By similarity
Metal binding8141Zinc 1 By similarity
Metal binding8171Zinc 1 By similarity
Metal binding8221Zinc 2 By similarity
Metal binding8301Zinc 2 By similarity

Amino acid modifications

Modified residue4151Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q66H62 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: 573B59E9BD795252

FASTA953106,713
        10         20         30         40         50         60 
MSSGLWNQEK VTSPYWEERL FYLLLQECSV TDKQTQKLLR VPKGSIGQYI QDRSVGHSRV 

        70         80         90        100        110        120 
PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERL SLFRNRIRLS 

       130        140        150        160        170        180 
KGLQVDVGSP VRVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 

       190        200        210        220        230        240 
YQGKQLFQCD EDCGVFVALD KLELIEDDDN GLESDFAGPG DTVQVEPPPL EINSRVSLKV 

       250        260        270        280        290        300 
GESTESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTVLLHIN 

       310        320        330        340        350        360 
DIIPDSVTQE RRPPKLAFMS RGVGDKGSSS HNKPKVTGST SDPGSRNRSE LFYTLNGSSV 

       370        380        390        400        410        420 
DSQQQSKSKN PWYIDEVAED PAKSLTEMSS DFGHSSPPPQ PPSMNSLSSE NRFHSLPFSL 

       430        440        450        460        470        480 
TKMPNTNGSM AHSPLSLSVQ SVMGELNSTP VQESPPMPSS SGNAHGLEVG SLAEVKENPP 

       490        500        510        520        530        540 
FYGVIRWIGQ PPGLSDVLAG LELEDECAGC TDGTFRGTRY FTCALKKALF VKLKSCRPDS 

       550        560        570        580        590        600 
RFASLQPVSN QIERCNSLAF GGYLSEVVEE NTPPKMEKEG LEIMIGKKKG IQGHYNSCYL 

       610        620        630        640        650        660 
DSTLFCLFAF SSALDTVLLR PKEKNDVEYY SETQELLRTE IVNPLRIYGY VCATKIMKLR 

       670        680        690        700        710        720 
KILEKVEAAS GFTSEEKDPE EFLNILFHDI LRVEPLLKIR SAGQKVQDCN FYQIFMEKNE 

       730        740        750        760        770        780 
KVGVPTIQQL LEWSFINSNL KFAEAPSCLI IQMPRFGKDF KLFKKIFPSL ELNITDLLED 

       790        800        810        820        830        840 
TPRQCRICGG LAMYECRECY DDPDISAGKI KQFCKTCSTQ VHLHPRRLNH TYHPVSLPKD 

       850        860        870        880        890        900 
LPDWDWRHGC IPCQKMELFA VLCIETSHYV AFVKYGKDDS AWLFFDSMAD RDGGQNGFNI 

       910        920        930        940        950 
PQVTPCPEVG EYLKMSLEDL HSLDSRRIQG CARRLLCDAY MCMYQSPTMS LYK 

« Hide

References

[1]"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].
Tissue: Testis.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC082001 mRNA. Translation: AAH82001.1.
RefSeqNP_001017380.1. NM_001017380.1.
UniGeneRn.128760.
Rn.168938.

3D structure databases

ProteinModelPortalQ66H62.
SMRQ66H62. Positions 125-206, 228-306, 462-547, 580-953.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid260280. 1 interaction.
STRING10116.ENSRNOP00000057517.

Protein family/group databases

MEROPSC67.001.

Proteomic databases

PaxDbQ66H62.
PRIDEQ66H62.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID312937.
KEGGrno:312937.

Organism-specific databases

CTD1540.
RGD1308346. Cyld.

Phylogenomic databases

eggNOGNOG313578.
HOGENOMHOG000006796.
HOVERGENHBG051281.
KOK08601.

Gene expression databases

GenevestigatorQ66H62.

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...

Other

NextBio665399.

Entry information

Entry nameCYLD_RAT
AccessionPrimary (citable) accession number: Q66H62
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: October 11, 2004
Last modified: February 19, 2014
This is version 80 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