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Q9NQC7 (CYLD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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, KIAA0849
ORF Names:HSPC057
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length956 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. 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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.22

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). Ref.22

Enzyme regulation

Inhibited by phosphorylation at serine residues. Ref.10

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18

Subcellular location

Cytoplasm. Cytoplasmperinuclear region. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase. Ref.9 Ref.11 Ref.13 Ref.15 Ref.16 Ref.22

Tissue specificity

Detected in fetal brain, testis, and skeletal muscle, and at a lower level in adult brain, leukocytes, liver, heart, kidney, spleen, ovary and lung. Isoform 2 is found in all tissues except kidney. Ref.1

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. Ref.10

Involvement in disease

Cylindromatosis, familial (FCYL) [MIM:132700]: A disorder characterized by multiple skin tumors that develop from skin appendages, such as hair follicles and sweat glands. Affected individuals typically develop large numbers of tumors called cylindromas that arise predominantly in hairy parts of the body with approximately 90% on the head and neck. In severely affected individuals, cylindromas may combine into a confluent mass which may ulcerate or become infected (turban tumor syndrome). Individuals with familial cylindromatosis occasionally develop other types of tumors including spiradenomas that begin in sweat glands, and trichoepitheliomas arising from hair follicles.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.26

Multiple familial trichoepithelioma 1 (MFT1) [MIM:601606]: Autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24 Ref.26

Brooke-Spiegler syndrome (BRSS) [MIM:605041]: An autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.21 Ref.23 Ref.25

Sequence similarities

Belongs to the peptidase C19 family.

Contains 3 CAP-Gly domains.

Contains 1 USP domain.

Sequence caution

The sequence AAF29029.1 differs from that shown. Reason: Frameshift at positions 776, 808 and 932.

The sequence BAA74872.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processCell cycle
Ubl conjugation pathway
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Microtubule
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Tumor suppressor
   DomainRepeat
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Protease
Thiol protease
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

necroptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of NF-kappaB import into nucleus

Inferred from direct assay Ref.22. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.22. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype Ref.17. Source: UniProtKB

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of extrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 21525013. Source: UniProtKB

protein K63-linked deubiquitination

Inferred from direct assay Ref.22Ref.12. Source: UniProtKB

regulation of intrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 21525013. Source: UniProtKB

regulation of microtubule cytoskeleton organization

Inferred from mutant phenotype Ref.15. Source: UniProtKB

regulation of mitotic cell cycle

Inferred from mutant phenotype Ref.11. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcentrosome

Inferred from direct assay. Source: HPA

cytosol

Inferred from direct assay Ref.22. Source: UniProtKB

extrinsic component of cytoplasmic side of plasma membrane

Inferred from direct assay Ref.15. Source: UniProtKB

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay. Source: HPA

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionLys63-specific deubiquitinase activity

Inferred from direct assay Ref.22. Source: UniProtKB

proline-rich region binding

Inferred from physical interaction Ref.18. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.12Ref.17. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.11Ref.12. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.22Ref.12. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.22. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NQC7-1)

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 2 (identifier: Q9NQC7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     305-307: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 956956Ubiquitin carboxyl-terminal hydrolase CYLD
PRO_0000080698

Regions

Domain153 – 19846CAP-Gly 1
Domain253 – 28634CAP-Gly 2
Domain492 – 53544CAP-Gly 3
Domain592 – 950359USP
Region106 – 593488Interaction with TRIP
Region394 – 46976Interaction with TRAF2
Region470 – 55485Interaction with IKBKG/NEMO

Sites

Active site6011Nucleophile Ref.22
Active site8711Proton acceptor Probable
Metal binding7881Zinc 1
Metal binding7911Zinc 1
Metal binding7991Zinc 2
Metal binding8021Zinc 2
Metal binding8171Zinc 1
Metal binding8201Zinc 1
Metal binding8251Zinc 2
Metal binding8331Zinc 2

Amino acid modifications

Modified residue4181Phosphoserine Ref.10

Natural variations

Alternative sequence305 – 3073Missing in isoform 2.
VSP_011277
Natural variant7471E → G in MFT1 and BRSS. Ref.23
VAR_045967

Experimental info

Mutagenesis4181S → A: Reduced phosphorylation; when associated with A-422; A-432 and A-436. Loss of phosphorylation; when associated with A-422; A-432; A-436; A-439; A-441 and A-444. Ref.10
Mutagenesis4181S → E: Abolishes deubiquitination of TRAF2; when associated with E-422; E-432; E-436; E-439; E-441 and E-444. Ref.10
Mutagenesis4221S → A: Reduced phosphorylation; when associated with A-418; A-432 and A-436. Loss of phosphorylation; when associated with A-418; A-432; A-436; A-439; A-441 and A-444. Ref.10
Mutagenesis4221S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-432; E-436; E-439; E-441 and E-444. Ref.10
Mutagenesis4321S → A: Slightly reduced phosphorylation; when associated with A-436. Reduced phosphorylation; when associated with A-418; A-422 and A-436. Loss of phosphorylation; when associated with A-418; A-422; A-436; A-439; A-441 and A-444. Ref.10
Mutagenesis4321S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-436; E-439; E-441 and E-444. Ref.10
Mutagenesis4361S → A: Slightly reduced phosphorylation; when associated with A-432. Reduced phosphorylation; when associated with A-418; A-422 and A-432. Loss of phosphorylation; when associated with A-418; A-422; A-432; A-439; A-441 and A-444. Ref.10
Mutagenesis4361S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-439; E-441 and E-444. Ref.10
Mutagenesis4391S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-441 and A-444. Ref.10
Mutagenesis4391S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-441 and E-444. Ref.10
Mutagenesis4411S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-444. Ref.10
Mutagenesis4411S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-444. Ref.10
Mutagenesis4441S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-441. Ref.10
Mutagenesis4441S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-441. Ref.10
Mutagenesis4571S → A: Abolishes binding to TRAF2. Ref.8
Mutagenesis6011C → A or S: Loss of deubiquitinating activity. Ref.6 Ref.7 Ref.11 Ref.22
Mutagenesis8711H → N: Loss of deubiquitinating activity. Ref.8

Secondary structure

........................................................................................................................... 956
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 01831F9A83424631

FASTA956107,316
        10         20         30         40         50         60 
MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRI 

        70         80         90        100        110        120 
PSAKGKKNQI 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 TTENRFHSLP 

       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 

« Hide

Isoform 2 [UniParc].

Checksum: 0CCB3D21E2FF8851
Show »

FASTA953107,044

References

« Hide 'large scale' references
[1]"Identification of the familial cylindromatosis tumor suppressor gene."
Bignell G.R., Brown C., Biggs P.J., Lakhani S.R., Jones C., Hansen J., Blair E., Hofmann B., Siebert R., Turner G., Evans D.G., Schrander-Stumpel C., Beemer F.A., Van Den Ouweland A., Halley D., Delpech B., Cleveland M.G., Leigh I. expand/collapse author list , Leisti J., Rasmussen S., Wallace M.R., Fenske C., Banerjee P., Oiso N., Chaggar R., Merrett S., Leonard N., Huber M., Hohl D., Chapman P., Burn J., Swift S., Smith A., Ashworth A., Stratton M.R.
Nat. Genet. 25:160-165(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INVOLVEMENT IN FAMILIAL CYLINDROMATOSIS.
[2]"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Uterus.
[5]"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. expand/collapse author list , Gu J., Chen S.-J., Chen Z.
Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 397-956.
Tissue: Umbilical cord blood.
[6]"CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members."
Trompouki E., Hatzivassiliou E., Tsichritzis T., Farmer H., Ashworth A., Mosialos G.
Nature 424:793-796(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IKBKG/NEMO, MUTAGENESIS OF CYS-601.
[7]"Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB."
Brummelkamp T.R., Nijman S.M.B., Dirac A.M.G., Bernards R.
Nature 424:797-801(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IKBKG/NEMO, MUTAGENESIS OF CYS-601.
[8]"The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination."
Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D., Courtois G.
Nature 424:801-805(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IKBKG/NEMO AND TRAF2, MUTAGENESIS OF SER-457 AND HIS-871.
[9]"The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor kappaB activation by tumor necrosis factor."
Regamey A., Hohl D., Liu J.W., Roger T., Kogerman P., Toftgaard R., Huber M.
J. Exp. Med. 198:1959-1964(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TRIP.
[10]"Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation."
Reiley W., Zhang M., Wu X., Granger E., Sun S.C.
Mol. Cell. Biol. 25:3886-3895(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TRAF2, ENZYME REGULATION, MUTAGENESIS OF SER-418; SER-422; SER-432; SER-436; SER-439; SER-441 AND SER-444, PHOSPHORYLATION AT SER-418.
[11]"The tumor suppressor CYLD regulates entry into mitosis."
Stegmeier F., Sowa M.E., Nalepa G., Gygi S.P., Harper J.W., Elledge S.J.
Proc. Natl. Acad. Sci. U.S.A. 104:8869-8874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-601, INTERACTION WITH PLK1, SUBCELLULAR LOCATION.
[12]"The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response."
Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A., Cardenas W.B., Yount J.S., Moran T.M., Basler C.F., Komuro A., Horvath C.M., Xavier R., Ting A.T.
EMBO Rep. 9:930-936(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH DDX58; MAVS; TBK1 AND IKKE.
[13]"The tumor suppressor CYLD regulates microtubule dynamics and plays a role in cell migration."
Gao J., Huo L., Sun X., Liu M., Li D., Dong J.T., Zhou J.
J. Biol. Chem. 283:8802-8809(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"CYLD regulates angiogenesis by mediating vascular endothelial cell migration."
Gao J., Sun L., Huo L., Liu M., Li D., Zhou J.
Blood 115:4130-4137(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[16]"CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin."
Wickstrom S.A., Masoumi K.C., Khochbin S., Fassler R., Massoumi R.
EMBO J. 29:131-144(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HDAC6; BCL3 AND MICROTUBULES, SUBCELLULAR LOCATION.
[17]"Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl."
Tauriello D.V., Haegebarth A., Kuper I., Edelmann M.J., Henraat M., Canninga-van Dijk M.R., Kessler B.M., Clevers H., Maurice M.M.
Mol. Cell 37:607-619(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DVL1 AND DVL3.
[18]"The CAP-Gly domain of CYLD associates with the proline-rich sequence in NEMO/IKKgamma."
Saito K., Kigawa T., Koshiba S., Sato K., Matsuo Y., Sakamoto A., Takagi T., Shirouzu M., Yabuki T., Nunokawa E., Seki E., Matsuda T., Aoki M., Miyata Y., Hirakawa N., Inoue M., Terada T., Nagase T. expand/collapse author list , Kikuno R., Nakayama M., Ohara O., Tanaka A., Yokoyama S.
Structure 12:1719-1728(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 460-550, INTERACTION WITH IKBKG.
[19]"Solution structure of the 1st and 2nd CAP-Gly domains in human cylindromatosis tumor suppressor CYLD."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2004) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 125-304.
[20]"Phenotype diversity in familial cylindromatosis: a frameshift mutation in the tumor suppressor gene CYLD underlies different tumors of skin appendages."
Poblete Gutierrez P., Eggermann T., Hoeller D., Jugert F.K., Beermann T., Grussendorf-Conen E.-I., Zerres K., Merk H.F., Frank J.
J. Invest. Dermatol. 119:527-531(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FCYL, INVOLVEMENT IN BRSS.
[21]"Identification of a recurrent mutation in the CYLD gene in Brooke-Spiegler syndrome."
Scheinfeld N., Hu G., Gill M., Austin C., Celebi J.T.
Clin. Exp. Dermatol. 28:539-541(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BRSS.
[22]"The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module."
Komander D., Lord C.J., Scheel H., Swift S., Hofmann K., Ashworth A., Barford D.
Mol. Cell 29:451-464(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 583-956 IN COMPLEX WITH ZINC IONS, FUNCTION, ACTIVE SITE, MUTAGENESIS OF CYS-601, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[23]"A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome."
Hu G., Oender M., Gill M., Aksakal B., Oeztas M., Guerer M.A., Celebi J.T.
J. Invest. Dermatol. 121:732-734(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MFT1 GLY-747, VARIANT BRSS GLY-747.
[24]"Two novel CYLD gene mutations in Chinese families with trichoepithelioma and a literature review of 16 families with trichoepithelioma reported in China."
Liang Y.H., Gao M., Sun L.D., Liu L.J., Cui Y., Yang S., Fan X., Wang J., Xiao F.L., Zhang X.J.
Br. J. Dermatol. 153:1213-1215(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MFT1.
[25]"Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation."
Bowen S., Gill M., Lee D.A., Fisher G., Geronemus R.G., Vazquez M.E., Celebi J.T.
J. Invest. Dermatol. 124:919-920(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BRSS.
[26]"CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes."
Young A.L., Kellermayer R., Szigeti R., Teszas A., Azmi S., Celebi J.T.
Clin. Genet. 70:246-249(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FCYL, INVOLVEMENT IN MFT1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ250014 mRNA. Translation: CAB93533.1.
AB020656 mRNA. Translation: BAA74872.2. Different initiation.
BC012342 mRNA. Translation: AAH12342.1.
AF161542 mRNA. Translation: AAF29029.1. Frameshift.
CCDSCCDS42164.1. [Q9NQC7-2]
CCDS45482.1. [Q9NQC7-1]
RefSeqNP_001035814.1. NM_001042355.1. [Q9NQC7-2]
NP_001035877.1. NM_001042412.1. [Q9NQC7-2]
NP_056062.1. NM_015247.2. [Q9NQC7-1]
XP_005255869.1. XM_005255812.2. [Q9NQC7-2]
XP_006721211.1. XM_006721148.1. [Q9NQC7-2]
XP_006721212.1. XM_006721149.1. [Q9NQC7-2]
XP_006721213.1. XM_006721150.1. [Q9NQC7-2]
XP_006721214.1. XM_006721151.1. [Q9NQC7-2]
UniGeneHs.578973.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IXDNMR-A460-550[»]
1WHLNMR-A125-206[»]
1WHMNMR-A228-304[»]
2VHFX-ray2.80A/B583-956[»]
ProteinModelPortalQ9NQC7.
SMRQ9NQC7. Positions 125-206, 228-307, 457-550, 583-956.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107920. 40 interactions.
IntActQ9NQC7. 23 interactions.
MINTMINT-6804518.
STRING9606.ENSP00000308928.

Protein family/group databases

MEROPSC67.001.

PTM databases

PhosphoSiteQ9NQC7.

Polymorphism databases

DMDM51316104.

Proteomic databases

MaxQBQ9NQC7.
PaxDbQ9NQC7.
PRIDEQ9NQC7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311559; ENSP00000308928; ENSG00000083799. [Q9NQC7-1]
ENST00000398568; ENSP00000381574; ENSG00000083799. [Q9NQC7-2]
ENST00000427738; ENSP00000392025; ENSG00000083799. [Q9NQC7-1]
ENST00000564326; ENSP00000454515; ENSG00000083799. [Q9NQC7-2]
ENST00000569418; ENSP00000457576; ENSG00000083799. [Q9NQC7-2]
GeneID1540.
KEGGhsa:1540.
UCSCuc002egp.1. human. [Q9NQC7-1]
uc002egq.1. human. [Q9NQC7-2]

Organism-specific databases

CTD1540.
GeneCardsGC16P050775.
HGNCHGNC:2584. CYLD.
HPACAB011713.
HPA050095.
MIM132700. phenotype.
601606. phenotype.
605018. gene.
605041. phenotype.
neXtProtNX_Q9NQC7.
Orphanet211. Familial cylindromatosis.
867. Familial multiple trichoepithelioma.
PharmGKBPA27084.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG313578.
HOGENOMHOG000006796.
HOVERGENHBG051281.
InParanoidQ9NQC7.
KOK08601.
OrthoDBEOG72ZCDM.
PhylomeDBQ9NQC7.
TreeFamTF318734.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9NQC7.
BgeeQ9NQC7.
CleanExHS_CYLD.
GenevestigatorQ9NQC7.

Family and domain databases

Gene3D2.30.30.190. 3 hits.
InterProIPR000938. CAP-Gly_domain.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF01302. CAP_GLY. 3 hits.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTSM01052. CAP_GLY. 3 hits.
[Graphical view]
SUPFAMSSF74924. SSF74924. 3 hits.
PROSITEPS00845. CAP_GLY_1. 1 hit.
PS50245. CAP_GLY_2. 2 hits.
PS00972. USP_1. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9NQC7.
GeneWikiCYLD_(gene).
GenomeRNAi1540.
NextBio6377.
PROQ9NQC7.
SOURCESearch...

Entry information

Entry nameCYLD_HUMAN
AccessionPrimary (citable) accession number: Q9NQC7
Secondary accession number(s): O94934 expand/collapse secondary AC list , Q7L3N6, Q96EH0, Q9NZX9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM