Q5RED8 (CYLD_PONAB) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CYLD
Synonyms:	CYLD1

Organism

Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]

Taxonomic identifier

9601 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Ponginae › Pongo

Protein attributes

Sequence length	956 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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 By similarity. 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.
Catalytic activity	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).
Subunit structure	Interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-rich C-terminal region). Interacts with TRAF2 and TRIP. Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and DDX58. Interacts (via CAP-Gly domain) with microtubules. Interacts with HDAC6 and BCL3. Interacts with SQSTM1 and MAP3K7. Identified in a complex with TRAF6 and SQSTM1 By similarity.
Subcellular location	Cytoplasm By similarity. Cytoplasm › perinuclear region By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase By similarity.
Post-translational modification	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.
Sequence similarities	Belongs to the peptidase C67 family. Contains 3 CAP-Gly domains.

Ontologies

Keywords
Biological process	Ubl conjugation pathway Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Microtubule
Domain	Repeat
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of NF-kappaB import into nucleus Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of canonical Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB protein K63-linked deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB microtubule Inferred from electronic annotation. Source: UniProtKB-KW perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 956	956	Ubiquitin carboxyl-terminal hydrolase CYLD		PRO_0000326148
Regions
	Domain	153 – 198	46	CAP-Gly 1
	Domain	253 – 286	34	CAP-Gly 2
	Domain	492 – 535	44	CAP-Gly 3
	Region	106 – 593	488	Interaction with TRIP
	Region	394 – 469	76	Interaction with TRAF2
	Region	470 – 684	215	Interaction with IKBKG/NEMO
Sites
	Active site	601	1	Nucleophile By similarity
	Active site	871	1	Proton acceptor By similarity
	Metal binding	788	1	Zinc 1 By similarity
	Metal binding	791	1	Zinc 1 By similarity
	Metal binding	799	1	Zinc 2 By similarity
	Metal binding	802	1	Zinc 2 By similarity
	Metal binding	817	1	Zinc 1 By similarity
	Metal binding	820	1	Zinc 1 By similarity
	Metal binding	825	1	Zinc 2 By similarity
	Metal binding	833	1	Zinc 2 By similarity
Amino acid modifications
	Modified residue	418	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q5RED8 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: ADDCE3C7241D828B	FASTA	956	107,302
	10 20 30 40 50 60 MSSGLWSQDK VTSPYWEERV FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRI 70 80 90 100 110 120 PSAKGKKNRI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERF SLFKNRNRLS 130 140 150 160 170 180 KGLQIDVGCP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 190 200 210 220 230 240 YQGKQLFQCD EDCGVFVALD KLELIEDDDT ALESDYAGPG DTMQVELPPL EINSRVSLKV 250 260 270 280 290 300 GETIESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAC VESTILLHIN 310 320 330 340 350 360 DIIPALSESV TQERRPPKLA FMSRGVGDKG SSSHNKPKAT GSTSDPGNRN RSELFYTLNG 370 380 390 400 410 420 SSVDSQPQSK SKNTWYIDEV AEDPAKSLTE ISTDFDRSSP PLQPPPVNSL STENRFHSLP 430 440 450 460 470 480 FSLTKMPNTN GSIGHSPLSL SAQSVMEELN TAPVQESPPL AMPPGNSHGL EVGSLAEVKE 490 500 510 520 530 540 NPPFYGVIRW IGQPPGLNEV LAGLELEDEC AGCTDGTFRG TRYFTCALKK ALFVKLKSCR 550 560 570 580 590 600 PDSRFASLQP VSNQIERCNS LAFGGYLSEV VEENTPPKME KEGLEIMIGK KKGIQGHYNS 610 620 630 640 650 660 CYLDSTLFCL FAFSSVLDTV LLRPKEKNDV EYYSETQELL RTEIVNPLRI YGYVCATKIM 670 680 690 700 710 720 KLRKILEKVE AASGFTSEEK DPEEFLNILF HHILRVEPLL KIRSAGQKVQ DCYFYQIFME 730 740 750 760 770 780 KNEKVGVPTI QQLLEWSFIN SNLKFAEAPS CLIIQMPRFG KDFKLFKKIF PSLELNITDL 790 800 810 820 830 840 LEDTPRQCRI CGGLAMYECR ECYDDPDISA GKIKQFCKTC NTQVHLHPKR LNHKYNPVSL 850 860 870 880 890 900 PKDLPDWDWR HGCIPCQNME LFAVLCIETS HYVAFVKYGK DDSAWLFFDS MADRDGGQNG 910 920 930 940 950 FNIPQVTPCP EVGEYLKMSL EDLHSLDSRR IQGCARRLLC DAYMCMYQSP TMSLYK

References

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

Cross-references

Sequence databases
EMBL GenBank DDBJ	CR857591 mRNA. Translation: CAH89869.1.
RefSeq	NP_001124871.1. NM_001131399.1.
UniGene	Pab.1922.
3D structure databases
HSSP	HSSP built from PDB template 1IXD based on UniProtKB Q9NQC7.
ProteinModelPortal	Q5RED8.
SMR	Q5RED8. Positions 125-206, 228-307, 457-550, 583-956.
ModBase	Search...
Protein family/group databases
MEROPS	C67.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100171734.
KEGG	pon:100171734.
Organism-specific databases
CTD	1540.
Phylogenomic databases
HOGENOM	HOG000006796.
HOVERGEN	HBG051281.
InParanoid	Q5RED8.
KO	K08601.
Family and domain databases
Gene3D	2.30.30.190. 3 hits.
InterPro	IPR000938. CAP-Gly_domain. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
Pfam	PF01302. CAP_GLY. 3 hits. PF00443. UCH. 1 hit. [Graphical view]
SMART	SM01052. CAP_GLY. 3 hits. [Graphical view]
SUPFAM	SSF74924. CAP-Gly_domain. 3 hits.
PROSITE	PS00845. CAP_GLY_1. 1 hit. PS50245. CAP_GLY_2. 2 hits. PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. False negative. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

CYLD_PONAB

Accession

Primary (citable) accession number: Q5RED8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	December 21, 2004
Last modified:	April 3, 2013
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program