CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022009
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase CYLD 
Protein Synonyms/Alias
 Deubiquitinating enzyme CYLD; Ubiquitin thioesterase CYLD; Ubiquitin-specific-processing protease CYLD 
Gene Name
 CYLD 
Gene Synonyms/Alias
 CYLD1; KIAA0849; HSPC057 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
121KNRNRLSKGLQIDVGubiquitination[1]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 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. 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). 
Sequence Annotation
 DOMAIN 153 198 CAP-Gly 1.
 DOMAIN 253 286 CAP-Gly 2.
 DOMAIN 492 535 CAP-Gly 3.
 REGION 106 593 Interaction with TRIP.
 REGION 394 469 Interaction with TRAF2.
 REGION 470 554 Interaction with IKBKG/NEMO.
 ACT_SITE 601 601 Nucleophile.
 ACT_SITE 871 871 Proton acceptor (Probable).
 METAL 788 788 Zinc 1.
 METAL 791 791 Zinc 1.
 METAL 799 799 Zinc 2.
 METAL 802 802 Zinc 2.
 METAL 817 817 Zinc 1.
 METAL 820 820 Zinc 1.
 METAL 825 825 Zinc 2.
 METAL 833 833 Zinc 2.
 MOD_RES 418 418 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Cell cycle; Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; Disease mutation; Hydrolase; Membrane; Metal-binding; Microtubule; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Tumor suppressor; Ubl conjugation pathway; Wnt signaling pathway; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 956 AA 
Protein Sequence
MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRI 60
PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERF SLFKNRNRLS 120
KGLQIDVGCP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 180
YQGKQLFQCD EDCGVFVALD KLELIEDDDT ALESDYAGPG DTMQVELPPL EINSRVSLKV 240
GETIESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAC VESTILLHIN 300
DIIPALSESV TQERRPPKLA FMSRGVGDKG SSSHNKPKAT GSTSDPGNRN RSELFYTLNG 360
SSVDSQPQSK SKNTWYIDEV AEDPAKSLTE ISTDFDRSSP PLQPPPVNSL TTENRFHSLP 420
FSLTKMPNTN GSIGHSPLSL SAQSVMEELN TAPVQESPPL AMPPGNSHGL EVGSLAEVKE 480
NPPFYGVIRW IGQPPGLNEV LAGLELEDEC AGCTDGTFRG TRYFTCALKK ALFVKLKSCR 540
PDSRFASLQP VSNQIERCNS LAFGGYLSEV VEENTPPKME KEGLEIMIGK KKGIQGHYNS 600
CYLDSTLFCL FAFSSVLDTV LLRPKEKNDV EYYSETQELL RTEIVNPLRI YGYVCATKIM 660
KLRKILEKVE AASGFTSEEK DPEEFLNILF HHILRVEPLL KIRSAGQKVQ DCYFYQIFME 720
KNEKVGVPTI QQLLEWSFIN SNLKFAEAPS CLIIQMPRFG KDFKLFKKIF PSLELNITDL 780
LEDTPRQCRI CGGLAMYECR ECYDDPDISA GKIKQFCKTC NTQVHLHPKR LNHKYNPVSL 840
PKDLPDWDWR HGCIPCQNME LFAVLCIETS HYVAFVKYGK DDSAWLFFDS MADRDGGQNG 900
FNIPQVTPCP EVGEYLKMSL EDLHSLDSRR IQGCARRLLC DAYMCMYQSP TMSLYK 956 
Gene Ontology
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0031234; C:extrinsic to internal side of plasma membrane; IDA:UniProtKB.
 GO:0005874; C:microtubule; IEA:UniProtKB-KW.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0006917; P:induction of apoptosis; IDA:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IMP:UniProtKB.
 GO:0042347; P:negative regulation of NF-kappaB import into nucleus; IDA:UniProtKB.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
 GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
 GO:0070507; P:regulation of microtubule cytoskeleton organization; IMP:UniProtKB.
 GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
Interpro
 IPR000938; CAP-Gly_domain.
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19. 
Pfam
 PF01302; CAP_GLY
 PF00443; UCH 
SMART
 SM01052; CAP_GLY 
PROSITE
 PS00845; CAP_GLY_1
 PS50245; CAP_GLY_2
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3 
PRINTS