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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

Cyld

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Deubiquitinase 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). Also able to remove linear ('Met-1'-linked) polyubiquitin chains to regulate innate immunity: recruited to the LUBAC complex and, together with OTULIN, restricts linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei598NucleophilePROSITE-ProRule annotation1
Metal bindingi785Zinc 1By similarity1
Metal bindingi788Zinc 1By similarity1
Metal bindingi796Zinc 2By similarity1
Metal bindingi799Zinc 2By similarity1
Metal bindingi814Zinc 1By similarity1
Metal bindingi817Zinc 1By similarity1
Metal bindingi822Zinc 2By similarity1
Metal bindingi830Zinc 2By similarity1
Active sitei868Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processImmunity, Innate immunity, Ubl conjugation pathway, Wnt signaling pathway
LigandMetal-binding, Zinc

Protein family/group databases

MEROPSiC67.001

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase CYLD (EC:3.4.19.12By similarity)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1308346 Cyld

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Microtubule

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003261491 – 953Ubiquitin carboxyl-terminal hydrolase CYLDAdd BLAST953

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei384PhosphoserineBy similarity1
Modified residuei415PhosphoserineCombined sources1
Modified residuei419PhosphoserineCombined sources1

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

PTM databases

iPTMnetiQ66H62
PhosphoSitePlusiQ66H62

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). Interacts with RNF31 (By similarity).By similarity

Protein-protein interaction databases

BioGridi260280, 2 interactors
STRINGi10116.ENSRNOP00000018888

Structurei

3D structure databases

ProteinModelPortaliQ66H62
SMRiQ66H62
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini153 – 198CAP-Gly 1PROSITE-ProRule annotationAdd BLAST46
Domaini253 – 286CAP-Gly 2PROSITE-ProRule annotationAdd BLAST34
Domaini489 – 532CAP-Gly 3PROSITE-ProRule annotationAdd BLAST44
Domaini589 – 947USPAdd BLAST359

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni106 – 590Interaction with TRIPBy similarityAdd BLAST485
Regioni391 – 466Interaction with TRAF2By similarityAdd BLAST76
Regioni467 – 681Interaction with IKBKG/NEMOBy similarityAdd BLAST215

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3556 Eukaryota
ENOG410XP6I LUCA
HOGENOMiHOG000006796
HOVERGENiHBG051281
InParanoidiQ66H62
KOiK08601
PhylomeDBiQ66H62

Family and domain databases

Gene3Di2.30.30.190, 3 hits
InterProiView protein in InterPro
IPR036859 CAP-Gly_dom_sf
IPR000938 CAP-Gly_domain
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF01302 CAP_GLY, 2 hits
PF00443 UCH, 1 hit
SMARTiView protein in SMART
SM01052 CAP_GLY, 3 hits
SUPFAMiSSF54001 SSF54001, 1 hit
SSF74924 SSF74924, 3 hits
PROSITEiView protein in PROSITE
PS00845 CAP_GLY_1, 1 hit
PS50245 CAP_GLY_2, 2 hits
PS00972 USP_1, 1 hit
PS50235 USP_3, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiCYLD_RAT
AccessioniPrimary (citable) accession number: Q66H62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: October 11, 2004
Last modified: June 20, 2018
This is version 108 of the entry and version 1 of the sequence. See 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

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