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Q66H62

- CYLD_RAT

UniProt

Q66H62 - CYLD_RAT

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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene
Cyld, Cyld1
Organism
Rattus norvegicus (Rat)
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 sitei598 – 5981Nucleophile By similarity
Metal bindingi785 – 7851Zinc 1 By similarity
Metal bindingi788 – 7881Zinc 1 By similarity
Metal bindingi796 – 7961Zinc 2 By similarity
Metal bindingi799 – 7991Zinc 2 By similarity
Metal bindingi814 – 8141Zinc 1 By similarity
Metal bindingi817 – 8171Zinc 1 By similarity
Metal bindingi822 – 8221Zinc 2 By similarity
Metal bindingi830 – 8301Zinc 2 By similarity
Active sitei868 – 8681Proton acceptor By similarity

GO - Molecular functioni

  1. Lys63-specific deubiquitinase activity Source: RefGenome
  2. ubiquitin-specific protease activity Source: UniProtKB
  3. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. necroptotic process Source: RefGenome
  2. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  3. negative regulation of NF-kappaB import into nucleus Source: UniProtKB
  4. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  5. positive regulation of extrinsic apoptotic signaling pathway Source: RefGenome
  6. protein K63-linked deubiquitination Source: UniProtKB
  7. regulation of intrinsic apoptotic signaling pathway Source: RefGenome
  8. regulation of mitotic cell cycle Source: RefGenome
  9. ubiquitin-dependent protein catabolic process Source: InterPro
  10. 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi1308346. Cyld.

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 – 953953Ubiquitin carboxyl-terminal hydrolase CYLDPRO_0000326149Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei415 – 4151Phosphoserine 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

Proteomic databases

PaxDbiQ66H62.
PRIDEiQ66H62.

Expressioni

Gene expression databases

GenevestigatoriQ66H62.

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.

Protein-protein interaction databases

BioGridi260280. 1 interaction.
STRINGi10116.ENSRNOP00000057517.

Structurei

3D structure databases

ProteinModelPortaliQ66H62.
SMRiQ66H62. Positions 125-206, 228-306, 462-547, 580-953.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini153 – 19846CAP-Gly 1Add
BLAST
Domaini253 – 28634CAP-Gly 2Add
BLAST
Domaini489 – 53244CAP-Gly 3Add
BLAST
Domaini589 – 947359USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni106 – 590485Interaction with TRIP By similarityAdd
BLAST
Regioni391 – 46676Interaction with TRAF2 By similarityAdd
BLAST
Regioni467 – 681215Interaction with IKBKG/NEMO By similarityAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG313578.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
KOiK08601.
PhylomeDBiQ66H62.

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.

Q66H62-1 [UniParc]FASTAAdd to Basket

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MSSGLWNQEK VTSPYWEERL FYLLLQECSV TDKQTQKLLR VPKGSIGQYI    50
QDRSVGHSRV PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL 100
LAITNCEERL SLFRNRIRLS KGLQVDVGSP VRVQLRSGEE KFPGVVRFRG 150
PLLAERTVSG IFFGVELLEE GRGQGFTDGV YQGKQLFQCD EDCGVFVALD 200
KLELIEDDDN GLESDFAGPG DTVQVEPPPL EINSRVSLKV GESTESGTVI 250
FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTVLLHIN 300
DIIPDSVTQE RRPPKLAFMS RGVGDKGSSS HNKPKVTGST SDPGSRNRSE 350
LFYTLNGSSV DSQQQSKSKN PWYIDEVAED PAKSLTEMSS DFGHSSPPPQ 400
PPSMNSLSSE NRFHSLPFSL TKMPNTNGSM AHSPLSLSVQ SVMGELNSTP 450
VQESPPMPSS SGNAHGLEVG SLAEVKENPP FYGVIRWIGQ PPGLSDVLAG 500
LELEDECAGC TDGTFRGTRY FTCALKKALF VKLKSCRPDS RFASLQPVSN 550
QIERCNSLAF GGYLSEVVEE NTPPKMEKEG LEIMIGKKKG IQGHYNSCYL 600
DSTLFCLFAF SSALDTVLLR PKEKNDVEYY SETQELLRTE IVNPLRIYGY 650
VCATKIMKLR KILEKVEAAS GFTSEEKDPE EFLNILFHDI LRVEPLLKIR 700
SAGQKVQDCN FYQIFMEKNE KVGVPTIQQL LEWSFINSNL KFAEAPSCLI 750
IQMPRFGKDF KLFKKIFPSL ELNITDLLED TPRQCRICGG LAMYECRECY 800
DDPDISAGKI KQFCKTCSTQ VHLHPRRLNH TYHPVSLPKD LPDWDWRHGC 850
IPCQKMELFA VLCIETSHYV AFVKYGKDDS AWLFFDSMAD RDGGQNGFNI 900
PQVTPCPEVG EYLKMSLEDL HSLDSRRIQG CARRLLCDAY MCMYQSPTMS 950
LYK 953
Length:953
Mass (Da):106,713
Last modified:October 11, 2004 - v1
Checksum:i573B59E9BD795252
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC082001 mRNA. Translation: AAH82001.1.
RefSeqiNP_001017380.1. NM_001017380.1.
UniGeneiRn.128760.
Rn.168938.

Genome annotation databases

GeneIDi312937.
KEGGirno:312937.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC082001 mRNA. Translation: AAH82001.1 .
RefSeqi NP_001017380.1. NM_001017380.1.
UniGenei Rn.128760.
Rn.168938.

3D structure databases

ProteinModelPortali Q66H62.
SMRi Q66H62. Positions 125-206, 228-306, 462-547, 580-953.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 260280. 1 interaction.
STRINGi 10116.ENSRNOP00000057517.

Protein family/group databases

MEROPSi C67.001.

Proteomic databases

PaxDbi Q66H62.
PRIDEi Q66H62.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 312937.
KEGGi rno:312937.

Organism-specific databases

CTDi 1540.
RGDi 1308346. Cyld.

Phylogenomic databases

eggNOGi NOG313578.
HOGENOMi HOG000006796.
HOVERGENi HBG051281.
KOi K08601.
PhylomeDBi Q66H62.

Miscellaneous databases

NextBioi 665399.

Gene expression databases

Genevestigatori Q66H62.

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 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.

Entry informationi

Entry nameiCYLD_RAT
AccessioniPrimary (citable) accession number: Q66H62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: October 11, 2004
Last modified: May 14, 2014
This is version 82 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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