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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

CYLD

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
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 sitei601 – 6011NucleophilePROSITE-ProRule annotation
Metal bindingi788 – 7881Zinc 1By similarity
Metal bindingi791 – 7911Zinc 1By similarity
Metal bindingi799 – 7991Zinc 2By similarity
Metal bindingi802 – 8021Zinc 2By similarity
Metal bindingi817 – 8171Zinc 1By similarity
Metal bindingi820 – 8201Zinc 1By similarity
Metal bindingi825 – 8251Zinc 2By similarity
Metal bindingi833 – 8331Zinc 2By similarity
Active sitei871 – 8711Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
ProteomesiUP000001595 Componenti: Unplaced

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

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 – 956956Ubiquitin carboxyl-terminal hydrolase CYLDPRO_0000326148Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei387 – 3871PhosphoserineBy similarity
Modified residuei418 – 4181PhosphoserineBy 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

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

STRINGi9601.ENSPPYP00000024661.

Structurei

3D structure databases

ProteinModelPortaliQ5RED8.
SMRiQ5RED8. Positions 125-206, 228-307, 457-550, 583-956.
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
Domaini492 – 53544CAP-Gly 3PROSITE-ProRule annotationAdd
BLAST
Domaini592 – 950359USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni106 – 593488Interaction with TRIPAdd
BLAST
Regioni394 – 46976Interaction with TRAF2Add
BLAST
Regioni470 – 684215Interaction with IKBKG/NEMOAdd
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

HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ5RED8.
KOiK08601.

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.

Q5RED8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSGLWSQDK VTSPYWEERV FYLLLQECSV TDKQTQKLLK VPKGSIGQYI
60 70 80 90 100
QDRSVGHSRI PSAKGKKNRI GLKILEQPHA VLFVDEKDVV EINEKFTELL
110 120 130 140 150
LAITNCEERF SLFKNRNRLS KGLQIDVGCP VKVQLRSGEE KFPGVVRFRG
160 170 180 190 200
PLLAERTVSG IFFGVELLEE GRGQGFTDGV YQGKQLFQCD EDCGVFVALD
210 220 230 240 250
KLELIEDDDT ALESDYAGPG DTMQVELPPL EINSRVSLKV GETIESGTVI
260 270 280 290 300
FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAC VESTILLHIN
310 320 330 340 350
DIIPALSESV TQERRPPKLA FMSRGVGDKG SSSHNKPKAT GSTSDPGNRN
360 370 380 390 400
RSELFYTLNG SSVDSQPQSK SKNTWYIDEV AEDPAKSLTE ISTDFDRSSP
410 420 430 440 450
PLQPPPVNSL STENRFHSLP FSLTKMPNTN GSIGHSPLSL SAQSVMEELN
460 470 480 490 500
TAPVQESPPL AMPPGNSHGL EVGSLAEVKE NPPFYGVIRW IGQPPGLNEV
510 520 530 540 550
LAGLELEDEC AGCTDGTFRG TRYFTCALKK ALFVKLKSCR PDSRFASLQP
560 570 580 590 600
VSNQIERCNS LAFGGYLSEV VEENTPPKME KEGLEIMIGK KKGIQGHYNS
610 620 630 640 650
CYLDSTLFCL FAFSSVLDTV LLRPKEKNDV EYYSETQELL RTEIVNPLRI
660 670 680 690 700
YGYVCATKIM KLRKILEKVE AASGFTSEEK DPEEFLNILF HHILRVEPLL
710 720 730 740 750
KIRSAGQKVQ DCYFYQIFME KNEKVGVPTI QQLLEWSFIN SNLKFAEAPS
760 770 780 790 800
CLIIQMPRFG KDFKLFKKIF PSLELNITDL LEDTPRQCRI CGGLAMYECR
810 820 830 840 850
ECYDDPDISA GKIKQFCKTC NTQVHLHPKR LNHKYNPVSL PKDLPDWDWR
860 870 880 890 900
HGCIPCQNME LFAVLCIETS HYVAFVKYGK DDSAWLFFDS MADRDGGQNG
910 920 930 940 950
FNIPQVTPCP EVGEYLKMSL EDLHSLDSRR IQGCARRLLC DAYMCMYQSP

TMSLYK
Length:956
Mass (Da):107,302
Last modified:December 21, 2004 - v1
Checksum:iADDCE3C7241D828B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857591 mRNA. Translation: CAH89869.1.
RefSeqiNP_001124871.1. NM_001131399.1.
UniGeneiPab.1922.

Genome annotation databases

GeneIDi100171734.
KEGGipon:100171734.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857591 mRNA. Translation: CAH89869.1.
RefSeqiNP_001124871.1. NM_001131399.1.
UniGeneiPab.1922.

3D structure databases

ProteinModelPortaliQ5RED8.
SMRiQ5RED8. Positions 125-206, 228-307, 457-550, 583-956.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000024661.

Protein family/group databases

MEROPSiC67.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100171734.
KEGGipon:100171734.

Organism-specific databases

CTDi1540.

Phylogenomic databases

HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ5RED8.
KOiK08601.

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

Entry informationi

Entry nameiCYLD_PONAB
AccessioniPrimary (citable) accession number: Q5RED8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 21, 2004
Last modified: June 24, 2015
This is version 69 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.