Reviewed, UniProtKB/Swiss-Prot Q80TQ2 (CYLD_MOUSE)

Names and origin

Protein names

Recommended name:
    Probable ubiquitin carboxyl-terminal hydrolase CYLD
    EC=3.1.2.15
Alternative name(s):
    Ubiquitin thioesterase CYLD
    Ubiquitin-specific-processing protease CYLD
    Deubiquitinating enzyme CYLD

Gene names

Name:	Cyld
Synonyms:	Cyld1, Kiaa0849

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	952 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Negative regulator of TRAF2 and NF-kappa-B signaling pathway. Has deubiquitinating activity that is directed towards non-'Lys-48'-linked polyubiquitin chains. The inhibition of NF-kappa-B activation is mediated at least in part, by the deubiquitination and inactivation of TRAF2 and, to a lesser extent, TRAF6 By similarity.
Catalytic activity	Ubiquitin C-terminal thioester + H2O = ubiquitin + a thiol.
Subunit structure	Interacts with NEMO, TRAF2 and TRIP By similarity.
Subcellular location	Cytoplasm › perinuclear region By similarity.
Sequence similarities	Belongs to the peptidase C67 family. Contains 2 CAP-Gly domains.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	translation Inferred from electronic annotation. Source: InterPro ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell ribosome Inferred from electronic annotation. Source: InterPro
Molecular function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct structural constituent of ribosome Inferred from electronic annotation. Source: InterPro ubiquitin thiolesterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Bcl3	Q9Z2F6	1	EBI-943859,EBI-943884

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q80TQ2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: Q80TQ2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     304-304: P → PALS

Isoform 3 (identifier: Q80TQ2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     305-318: DSVTQERRPPKLAF → GTSKNILDQQLKGK
     319-952: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 952	952	Probable ubiquitin carboxyl-terminal hydrolase CYLD		PRO_0000080699
Regions
	Domain	153 – 198	46	CAP-Gly 1
	Domain	488 – 531	44	CAP-Gly 2
	Region	106 – 589	484	Interaction with TRIP By similarity
	Region	390 – 465	76	Interaction with TRAF2 By similarity
	Region	466 – 680	215	Interaction with NEMO By similarity
Sites
	Active site	597	1	By similarity
	Active site	867	1	By similarity
Amino acid modifications
	Modified residue	395	1	Phosphoserine By similarity
	Modified residue	414	1	Phosphoserine Ref.4
Natural variations
	Alternative sequence	304	1	P → PALS in isoform 1.		VSP_011278
	Alternative sequence	305 – 318	14	DSVTQ…PKLAF → GTSKNILDQQLKGK in isoform 3.		VSP_011279
	Alternative sequence	319 – 952	634	Missing in isoform 3.		VSP_011280
Experimental info
	Sequence conflict	403	1	M → V in BAC30222. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 0AC0C7D4FF215A9C	FASTA	952	106,586
	10 20 30 40 50 60 MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRV 70 80 90 100 110 120 PSTKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERL SLFRNRLRLS 130 140 150 160 170 180 KGLQVDVGSP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 190 200 210 220 230 240 YQGKQLFQCD EDCGVFVALD KLELIEDDDN GLESDFAGPG DTMQVEPPPL EINSRVSLKV 250 260 270 280 290 300 GESTESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTILLHIN 310 320 330 340 350 360 DIIPDSVTQE RRPPKLAFMS RGVGDKGSSS HNKPKVTGST SDPGSRNRSE LFYTLNGSSV 370 380 390 400 410 420 DSQQSKSKNP WYIDEVAEDP AKSLTEMSSD FGHSSPPPQP PSMNSLSSEN RFHSLPFSLT 430 440 450 460 470 480 KMPNTNGSMA HSPLSLSVQS VMGELNSTPV QESPPLPISS GNAHGLEVGS LAEVKENPPF 490 500 510 520 530 540 YGVIRWIGQP PGLSDVLAGL ELEDECAGCT DGTFRGTRYF TCALKKALFV KLKSCRPDSR 550 560 570 580 590 600 FASLQPVSNQ IERCNSLAFG GYLSEVVEEN TPPKMEKEGL EIMIGKKKGI QGHYNSCYLD 610 620 630 640 650 660 STLFCLFAFS SALDTVLLRP KEKNDIEYYS ETQELLRTEI VNPLRIYGYV CATKIMKLRK 670 680 690 700 710 720 ILEKVEAASG FTSEEKDPEE FLNILFHDIL RVEPLLKIRS AGQKVQDCNF YQIFMEKNEK 730 740 750 760 770 780 VGVPTIQQLL EWSFINSNLK FAEAPSCLII QMPRFGKDFK LFKKIFPSLE LNITDLLEDT 790 800 810 820 830 840 PRQCRICGGL AMYECRECYD DPDISAGKIK QFCKTCSTQV HLHPRRLNHS YHPVSLPKDL 850 860 870 880 890 900 PDWDWRHGCI PCQKMELFAV LCIETSHYVA FVKYGKDDSA WLFFDSMADR DGGQNGFNIP 910 920 930 940 950 QVTPCPEVGE YLKMSLEDLH SLDSRRIQGC ARRLLCDAYM CMYQSPTMSL YK
	Isoform 1. Checksum: E8D55AE26D90241F	FASTA	955	106,857
	10 20 30 40 50 60 MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRV 70 80 90 100 110 120 PSTKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERL SLFRNRLRLS 130 140 150 160 170 180 KGLQVDVGSP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 190 200 210 220 230 240 YQGKQLFQCD EDCGVFVALD KLELIEDDDN GLESDFAGPG DTMQVEPPPL EINSRVSLKV 250 260 270 280 290 300 GESTESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTILLHIN 310 320 330 340 350 360 DIIPALSDSV TQERRPPKLA FMSRGVGDKG SSSHNKPKVT GSTSDPGSRN RSELFYTLNG 370 380 390 400 410 420 SSVDSQQSKS KNPWYIDEVA EDPAKSLTEM SSDFGHSSPP PQPPSMNSLS SENRFHSLPF 430 440 450 460 470 480 SLTKMPNTNG SMAHSPLSLS VQSVMGELNS TPVQESPPLP ISSGNAHGLE VGSLAEVKEN 490 500 510 520 530 540 PPFYGVIRWI GQPPGLSDVL AGLELEDECA GCTDGTFRGT RYFTCALKKA LFVKLKSCRP 550 560 570 580 590 600 DSRFASLQPV SNQIERCNSL AFGGYLSEVV EENTPPKMEK EGLEIMIGKK KGIQGHYNSC 610 620 630 640 650 660 YLDSTLFCLF AFSSALDTVL LRPKEKNDIE YYSETQELLR TEIVNPLRIY GYVCATKIMK 670 680 690 700 710 720 LRKILEKVEA ASGFTSEEKD PEEFLNILFH DILRVEPLLK IRSAGQKVQD CNFYQIFMEK 730 740 750 760 770 780 NEKVGVPTIQ QLLEWSFINS NLKFAEAPSC LIIQMPRFGK DFKLFKKIFP SLELNITDLL 790 800 810 820 830 840 EDTPRQCRIC GGLAMYECRE CYDDPDISAG KIKQFCKTCS TQVHLHPRRL NHSYHPVSLP 850 860 870 880 890 900 KDLPDWDWRH GCIPCQKMEL FAVLCIETSH YVAFVKYGKD DSAWLFFDSM ADRDGGQNGF 910 920 930 940 950 NIPQVTPCPE VGEYLKMSLE DLHSLDSRRI QGCARRLLCD AYMCMYQSPT MSLYK
	Isoform 3. Checksum: 23465D36304356BF	FASTA	318	35,288
	10 20 30 40 50 60 MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRV 70 80 90 100 110 120 PSTKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERL SLFRNRLRLS 130 140 150 160 170 180 KGLQVDVGSP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV 190 200 210 220 230 240 YQGKQLFQCD EDCGVFVALD KLELIEDDDN GLESDFAGPG DTMQVEPPPL EINSRVSLKV 250 260 270 280 290 300 GESTESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTILLHIN 310 DIIPGTSKNI LDQQLKGK

References

[1]	"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H. DNA Res. 10:35-48(2003) [PubMed: 12693553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-620 (ISOFORM 1). Strain: C57BL/6J. Tissue: Cerebellum and Hypothalamus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Mammary gland.
[4]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 18973353] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK122389 mRNA. Translation: BAC65671.1. Different initiation. AK039054 mRNA. Translation: BAC30222.1. AK042764 mRNA. Translation: BAC31357.1. BC042438 mRNA. Translation: AAH42438.1. BC049879 mRNA. Translation: AAH49879.1.
IPI	IPI00277703. IPI00463126. IPI00875098.
RefSeq	NP_001121641.1. NP_001121642.1. NP_001121643.1. NP_775545.1.
UniGene	Mm.24282
3D structure databases
SMR	Q80TQ2. Positions 125-206, 228-306, 453-546.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q80TQ2. 1 interaction.
STRING	Q80TQ2.
PTM databases
PhosphoSite	Q80TQ2.
Proteomic databases
PRIDE	Q80TQ2.
Genome annotation databases
Ensembl	ENSMUST00000043526; ENSMUSP00000039834; ENSMUSG00000036712; Mus musculus. [Genome view] ENSMUST00000109622; ENSMUSP00000105251; ENSMUSG00000036712; Mus musculus. [Genome view] ENSMUST00000109626; ENSMUSP00000105254; ENSMUSG00000036712; Mus musculus. [Genome view]
GeneID	74256.
KEGG	mmu:74256.
UCSC	uc009mrt.1. mouse. uc009mrw.1. mouse.
Organism-specific databases
CTD	74256.
MGI	MGI:1921506. Cyld.
Rouge	Search...
Phylogenomic databases
HOGENOM	Q80TQ2.
HOVERGEN	Q80TQ2.
OMA	GVQLCSF.
Enzyme and pathway databases
BRENDA	3.1.2.15. 244.
Gene expression databases
ArrayExpress	Q80TQ2.
Bgee	Q80TQ2.
CleanEx	MM_CYLD.
Genevestigator	Q80TQ2.
GermOnline	ENSMUSG00000036712. Mus musculus.
Family and domain databases
InterPro	IPR000938. Cytoskel-assoc-prot_CAP-Gly. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR001593. Ribosomal_S3Ae. [Graphical view]
PANTHER	PTHR11830. Ribosomal_S3AE. 1 hit.
Pfam	PF01302. CAP_GLY. 3 hits. PF00443. UCH. 1 hit. [Graphical view]
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...
Other Resources
NextBio	340262.
SOURCE	Search...

Entry information

Entry name

CYLD_MOUSE

Accession

Primary (citable) accession number: Q80TQ2
Secondary accession number(s): Q80VB3 , Q8BXZ3, Q8BYL9, Q8CGB0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	August 16, 2004
Last modified:	November 3, 2009
This is version 62 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)