Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

CYLD

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Immunity, Innate immunity, Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-5357786. TNFR1-induced proapoptotic signaling.
R-BTA-5357905. Regulation of TNFR1 signaling.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5689880. Ub-specific processing proteases.
R-BTA-936440. Negative regulators of RIG-I/MDA5 signaling.

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 18

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)DescriptionActionsGraphical viewLength
ChainiPRO_00003261471 – 953Ubiquitin carboxyl-terminal hydrolase CYLDAdd BLAST953

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei384PhosphoserineBy similarity1
Modified residuei415PhosphoserineBy similarity1
Modified residuei419PhosphoserineBy similarity1

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

PaxDbiQ1RMU2.
PRIDEiQ1RMU2.

Expressioni

Gene expression databases

BgeeiENSBTAG00000006291.

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

STRINGi9913.ENSBTAP00000008257.

Structurei

3D structure databases

ProteinModelPortaliQ1RMU2.
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
Contains 3 CAP-Gly domains.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3556. Eukaryota.
ENOG410XP6I. LUCA.
GeneTreeiENSGT00390000018123.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ1RMU2.
KOiK08601.
OMAiCTDGTFK.
OrthoDBiEOG091G015D.
TreeFamiTF318734.

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. 2 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.

Q1RMU2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQNI
60 70 80 90 100
QDRSVGLSRI PSAKGKKNQI 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 GLESDYAGPV DTMQVELPPL EINSRVSLKL GETIESGTVI
260 270 280 290 300
FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTILLHIN
310 320 330 340 350
DIIPESVTQE RRPPKLAFMS RGVGDKGSFS HNKPKATGST SDPGTRNRSE
360 370 380 390 400
LFYTLNGSSV DSQPQSKSKN SWYIDEVAED PAKSLTEIPP DFGHASPPLQ
410 420 430 440 450
PPSMNSLSSE NRFHSLPFSL TKMPNTNGSI SHSPLSLSVQ SVMGELNNAP
460 470 480 490 500
VQESPPLAVS SGNSHGLEVG SLAEVKENPP FYGVIRWIGQ PPGLNEVLAG
510 520 530 540 550
LELEDECAGC TDGTFRGTRY FTCALKKALF VKLKSCRPDS RFASLQPVSN
560 570 580 590 600
QIERCNSLAF GGYLSEVVEE NTPPKMEKEG FEIMIGKKKG IQGHYNSCYL
610 620 630 640 650
DSTLFCLFAF SSVLDTVLLR PKEKNDVEYY SETQELLRTE IVNPLRIYGY
660 670 680 690 700
VCATKIMKLR KILEKVEAAS GFTSEEKDPE EFLNILFHHI LRVEPLLKIR
710 720 730 740 750
SAGQKVQDCY FYQIFMEKNE KVGVPTIQQL LECSFINSNL KFAEAPSCLI
760 770 780 790 800
IQMPRFGKDF KLFKKIFPSL ELNITDLLED TPRQCRICGG LAMYECRECY
810 820 830 840 850
DDPDISAGKI KQFCKTCNAQ VHLHPKRLNH KYNPVSLPKD LPDWDWRHGC
860 870 880 890 900
IPCQKMELFA VLCIETSHYV AFVKYGKDDS AWLFFDSMAD RDGGQNGFNI
910 920 930 940 950
PQVTPCPEVG EYLKMSLDDL HSLDSRRIQG CARRLLCDAY MCMYQSPTMS

LYK
Length:953
Mass (Da):106,805
Last modified:May 16, 2006 - v1
Checksum:iF478EBCB7D52863E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC114710 mRNA. Translation: AAI14711.1.
RefSeqiNP_001039882.1. NM_001046417.1.
XP_005218741.1. XM_005218684.2.
XP_010812839.1. XM_010814537.2.
UniGeneiBt.58637.

Genome annotation databases

EnsembliENSBTAT00000008257; ENSBTAP00000008257; ENSBTAG00000006291.
GeneIDi536421.
KEGGibta:536421.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC114710 mRNA. Translation: AAI14711.1.
RefSeqiNP_001039882.1. NM_001046417.1.
XP_005218741.1. XM_005218684.2.
XP_010812839.1. XM_010814537.2.
UniGeneiBt.58637.

3D structure databases

ProteinModelPortaliQ1RMU2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000008257.

Protein family/group databases

MEROPSiC67.001.

Proteomic databases

PaxDbiQ1RMU2.
PRIDEiQ1RMU2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000008257; ENSBTAP00000008257; ENSBTAG00000006291.
GeneIDi536421.
KEGGibta:536421.

Organism-specific databases

CTDi1540.

Phylogenomic databases

eggNOGiKOG3556. Eukaryota.
ENOG410XP6I. LUCA.
GeneTreeiENSGT00390000018123.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ1RMU2.
KOiK08601.
OMAiCTDGTFK.
OrthoDBiEOG091G015D.
TreeFamiTF318734.

Enzyme and pathway databases

ReactomeiR-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-5357786. TNFR1-induced proapoptotic signaling.
R-BTA-5357905. Regulation of TNFR1 signaling.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5689880. Ub-specific processing proteases.
R-BTA-936440. Negative regulators of RIG-I/MDA5 signaling.

Gene expression databases

BgeeiENSBTAG00000006291.

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. 2 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...

Entry informationi

Entry nameiCYLD_BOVIN
AccessioniPrimary (citable) accession number: Q1RMU2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: May 16, 2006
Last modified: November 30, 2016
This is version 86 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

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 one 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.