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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

Cyld

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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 (By similarity). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (By similarity). Negative regulator of Wnt signaling (By similarity). Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules (By similarity). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (By similarity). Required for normal cell cycle progress and normal cytokinesis (By similarity). 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 (By similarity). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (By similarity). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (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 sitei598 – 5981NucleophilePROSITE-ProRule annotation
Metal bindingi785 – 7851Zinc 1By similarity
Metal bindingi788 – 7881Zinc 1By similarity
Metal bindingi796 – 7961Zinc 2By similarity
Metal bindingi799 – 7991Zinc 2By similarity
Metal bindingi814 – 8141Zinc 1By similarity
Metal bindingi817 – 8171Zinc 1By similarity
Metal bindingi822 – 8221Zinc 2By similarity
Metal bindingi830 – 8301Zinc 2By similarity
Active sitei868 – 8681Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  1. necroptotic process Source: GO_Central
  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: GO_Central
  6. protein K63-linked deubiquitination Source: UniProtKB
  7. regulation of cilium assembly Source: UniProtKB
  8. regulation of intrinsic apoptotic signaling pathway Source: GO_Central
  9. regulation of mitotic cell cycle Source: GO_Central
  10. ubiquitin-dependent protein catabolic process Source: InterPro
  11. 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 Componenti: Unplaced

Organism-specific databases

RGDi1308346. Cyld.

Subcellular locationi

Cytoplasm. Cytoplasmperinuclear region. Cytoplasmcytoskeleton. Cell membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmcytoskeletonspindle By similarity. Cytoplasmcytoskeletoncilium basal body By similarity
Note: Detected at the microtubule cytoskeleton during interphase (By similarity). Detected at the midbody during telophase (By similarity). During metaphase, it remains localized to the centrosome but is also present along the spindle (By similarity).By similarity

GO - Cellular componenti

  1. centrosome Source: UniProtKB
  2. ciliary basal body Source: UniProtKB
  3. ciliary tip Source: UniProtKB
  4. cytosol Source: UniProtKB
  5. microtubule Source: UniProtKB-KW
  6. perinuclear region of cytoplasm Source: UniProtKB-SubCell
  7. plasma membrane Source: UniProtKB-SubCell
  8. spindle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, 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 residuei384 – 3841PhosphoserineBy similarity
Modified residuei415 – 4151PhosphoserineBy 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

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) (By similarity). Interacts with TRAF2 and TRIP (By similarity). Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and DDX58 (By similarity). Interacts (via CAP-Gly domain) with microtubules (By similarity). Interacts with HDAC6 and BCL3 (By similarity). Interacts with SQSTM1 and MAP3K7 (By similarity). Identified in a complex with TRAF6 and SQSTM1 (By similarity). Interacts with CEP350 (By similarity).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.
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
Domaini489 – 53244CAP-Gly 3PROSITE-ProRule annotationAdd
BLAST
Domaini589 – 947359USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni106 – 590485Interaction with TRIPBy similarityAdd
BLAST
Regioni391 – 46676Interaction with TRAF2By similarityAdd
BLAST
Regioni467 – 681215Interaction with IKBKG/NEMOBy similarityAdd
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

eggNOGiNOG313578.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ66H62.
KOiK08601.
PhylomeDBiQ66H62.

Family and domain databases

Gene3Di2.30.30.190. 3 hits.
InterProiIPR000938. CAP-Gly_domain.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[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

« Hide

        10         20         30         40         50
MSSGLWNQEK VTSPYWEERL FYLLLQECSV TDKQTQKLLR VPKGSIGQYI
60 70 80 90 100
QDRSVGHSRV PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL
110 120 130 140 150
LAITNCEERL SLFRNRIRLS KGLQVDVGSP VRVQLRSGEE KFPGVVRFRG
160 170 180 190 200
PLLAERTVSG IFFGVELLEE GRGQGFTDGV YQGKQLFQCD EDCGVFVALD
210 220 230 240 250
KLELIEDDDN GLESDFAGPG DTVQVEPPPL EINSRVSLKV GESTESGTVI
260 270 280 290 300
FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTVLLHIN
310 320 330 340 350
DIIPDSVTQE RRPPKLAFMS RGVGDKGSSS HNKPKVTGST SDPGSRNRSE
360 370 380 390 400
LFYTLNGSSV DSQQQSKSKN PWYIDEVAED PAKSLTEMSS DFGHSSPPPQ
410 420 430 440 450
PPSMNSLSSE NRFHSLPFSL TKMPNTNGSM AHSPLSLSVQ SVMGELNSTP
460 470 480 490 500
VQESPPMPSS SGNAHGLEVG SLAEVKENPP FYGVIRWIGQ PPGLSDVLAG
510 520 530 540 550
LELEDECAGC TDGTFRGTRY FTCALKKALF VKLKSCRPDS RFASLQPVSN
560 570 580 590 600
QIERCNSLAF GGYLSEVVEE NTPPKMEKEG LEIMIGKKKG IQGHYNSCYL
610 620 630 640 650
DSTLFCLFAF SSALDTVLLR PKEKNDVEYY SETQELLRTE IVNPLRIYGY
660 670 680 690 700
VCATKIMKLR KILEKVEAAS GFTSEEKDPE EFLNILFHDI LRVEPLLKIR
710 720 730 740 750
SAGQKVQDCN FYQIFMEKNE KVGVPTIQQL LEWSFINSNL KFAEAPSCLI
760 770 780 790 800
IQMPRFGKDF KLFKKIFPSL ELNITDLLED TPRQCRICGG LAMYECRECY
810 820 830 840 850
DDPDISAGKI KQFCKTCSTQ VHLHPRRLNH TYHPVSLPKD LPDWDWRHGC
860 870 880 890 900
IPCQKMELFA VLCIETSHYV AFVKYGKDDS AWLFFDSMAD RDGGQNGFNI
910 920 930 940 950
PQVTPCPEVG EYLKMSLEDL HSLDSRRIQG CARRLLCDAY MCMYQSPTMS

LYK
Length:953
Mass (Da):106,713
Last modified:October 11, 2004 - v1
Checksum:i573B59E9BD795252
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
BC082001 mRNA. Translation: AAH82001.1.
RefSeqiNP_001017380.1. NM_001017380.1.
UniGeneiRn.128760.
Rn.168938.

3D structure databases

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

Protein-protein interaction databases

BioGridi260280. 1 interaction.
STRINGi10116.ENSRNOP00000057517.

Protein family/group databases

MEROPSiC67.001.

Proteomic databases

PaxDbiQ66H62.
PRIDEiQ66H62.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi312937.
KEGGirno:312937.

Organism-specific databases

CTDi1540.
RGDi1308346. Cyld.

Phylogenomic databases

eggNOGiNOG313578.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ66H62.
KOiK08601.
PhylomeDBiQ66H62.

Miscellaneous databases

NextBioi665399.

Gene expression databases

GenevestigatoriQ66H62.

Family and domain databases

Gene3Di2.30.30.190. 3 hits.
InterProiIPR000938. CAP-Gly_domain.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[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]
ProtoNetiSearch...

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(2003) [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: March 4, 2015
This is version 87 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.