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Q9NQC7

- CYLD_HUMAN

UniProt

Q9NQC7 - CYLD_HUMAN

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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene
CYLD, CYLD1, KIAA0849, HSPC057
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.12 Publications

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).1 Publication

Enzyme regulationi

Inhibited by phosphorylation at serine residues.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei601 – 6011Nucleophile1 Publication
Metal bindingi788 – 7881Zinc 1
Metal bindingi791 – 7911Zinc 1
Metal bindingi799 – 7991Zinc 2
Metal bindingi802 – 8021Zinc 2
Metal bindingi817 – 8171Zinc 1
Metal bindingi820 – 8201Zinc 1
Metal bindingi825 – 8251Zinc 2
Metal bindingi833 – 8331Zinc 2
Active sitei871 – 8711Proton acceptor Inferred

GO - Molecular functioni

  1. Lys63-specific deubiquitinase activity Source: UniProtKB
  2. proline-rich region binding Source: UniProtKB
  3. protein binding Source: UniProtKB
  4. protein kinase binding Source: UniProtKB
  5. ubiquitin-specific protease activity Source: UniProtKB
  6. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. innate immune response Source: Reactome
  3. necroptotic process Source: RefGenome
  4. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  5. negative regulation of NF-kappaB import into nucleus Source: UniProtKB
  6. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  7. negative regulation of type I interferon production Source: Reactome
  8. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
  9. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  10. positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  11. protein K63-linked deubiquitination Source: UniProtKB
  12. regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  13. regulation of microtubule cytoskeleton organization Source: UniProtKB
  14. regulation of mitotic cell cycle Source: UniProtKB
  15. ubiquitin-dependent protein catabolic process Source: InterPro
  16. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Cell cycle, Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_75776. NOD1/2 Signaling Pathway.

Protein family/group databases

MEROPSiC67.001.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CYLD
Synonyms:CYLD1, KIAA0849
ORF Names:HSPC057
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:2584. CYLD.

Subcellular locationi

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.6 Publications

GO - Cellular componenti

  1. centrosome Source: HPA
  2. cytosol Source: UniProtKB
  3. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  4. microtubule Source: UniProtKB-KW
  5. nucleus Source: HPA
  6. perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Microtubule

Pathology & Biotechi

Involvement in diseasei

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.2 Publications
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.3 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti747 – 7471E → G in MFT1 and BRSS. 1 Publication
VAR_045967
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.4 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti747 – 7471E → G in MFT1 and BRSS. 1 Publication
VAR_045967

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi418 – 4181S → 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. 1 Publication
Mutagenesisi418 – 4181S → E: Abolishes deubiquitination of TRAF2; when associated with E-422; E-432; E-436; E-439; E-441 and E-444. 1 Publication
Mutagenesisi422 – 4221S → 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. 1 Publication
Mutagenesisi422 – 4221S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-432; E-436; E-439; E-441 and E-444. 1 Publication
Mutagenesisi432 – 4321S → 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. 1 Publication
Mutagenesisi432 – 4321S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-436; E-439; E-441 and E-444. 1 Publication
Mutagenesisi436 – 4361S → 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. 1 Publication
Mutagenesisi436 – 4361S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-439; E-441 and E-444. 1 Publication
Mutagenesisi439 – 4391S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-441 and A-444. 1 Publication
Mutagenesisi439 – 4391S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-441 and E-444. 1 Publication
Mutagenesisi441 – 4411S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-444. 1 Publication
Mutagenesisi441 – 4411S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-444. 1 Publication
Mutagenesisi444 – 4441S → A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-441. 1 Publication
Mutagenesisi444 – 4441S → E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-441. 1 Publication
Mutagenesisi457 – 4571S → A: Abolishes binding to TRAF2. 1 Publication
Mutagenesisi601 – 6011C → A or S: Loss of deubiquitinating activity. 4 Publications
Mutagenesisi871 – 8711H → N: Loss of deubiquitinating activity. 1 Publication

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

MIMi132700. phenotype.
601606. phenotype.
605041. phenotype.
Orphaneti211. Familial cylindromatosis.
867. Familial multiple trichoepithelioma.
PharmGKBiPA27084.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 956956Ubiquitin carboxyl-terminal hydrolase CYLDPRO_0000080698Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei418 – 4181Phosphoserine1 Publication

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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NQC7.
PaxDbiQ9NQC7.
PRIDEiQ9NQC7.

PTM databases

PhosphoSiteiQ9NQC7.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

ArrayExpressiQ9NQC7.
BgeeiQ9NQC7.
CleanExiHS_CYLD.
GenevestigatoriQ9NQC7.

Organism-specific databases

HPAiCAB011713.
HPA050095.

Interactioni

Subunit structurei

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.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DDX58O957862EBI-2117940,EBI-995350
HDAC6Q9UBN74EBI-2117940,EBI-301697
ITCHQ96J023EBI-2117940,EBI-1564678
ITCHQ96J02-22EBI-2117940,EBI-6672198
TUBA1AQ71U366EBI-2117940,EBI-302552

Protein-protein interaction databases

BioGridi107920. 40 interactions.
IntActiQ9NQC7. 23 interactions.
MINTiMINT-6804518.
STRINGi9606.ENSP00000308928.

Structurei

Secondary structure

1
956
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi130 – 1345
Beta strandi136 – 1394
Beta strandi141 – 1499
Beta strandi154 – 1574
Beta strandi163 – 1675
Beta strandi169 – 1713
Turni191 – 1933
Beta strandi194 – 1974
Helixi199 – 2013
Beta strandi202 – 2043
Beta strandi235 – 2406
Beta strandi243 – 25311
Turni259 – 2613
Beta strandi264 – 2729
Beta strandi278 – 2803
Beta strandi283 – 2853
Beta strandi293 – 2986
Helixi299 – 3013
Beta strandi302 – 3043
Turni463 – 4653
Beta strandi466 – 4683
Beta strandi474 – 4785
Beta strandi480 – 4823
Beta strandi486 – 4927
Beta strandi495 – 4973
Beta strandi501 – 5088
Beta strandi514 – 5185
Beta strandi531 – 5355
Helixi536 – 5383
Beta strandi539 – 5413
Helixi584 – 5863
Beta strandi588 – 5914
Helixi601 – 61111
Beta strandi612 – 6143
Helixi615 – 6173
Helixi618 – 6225
Helixi633 – 64210
Helixi645 – 6506
Beta strandi652 – 6543
Helixi656 – 66914
Helixi682 – 6909
Turni691 – 6944
Beta strandi699 – 7046
Beta strandi710 – 7134
Helixi730 – 74112
Beta strandi743 – 7475
Beta strandi750 – 7556
Beta strandi760 – 7645
Beta strandi773 – 7753
Helixi778 – 7803
Beta strandi781 – 7844
Turni789 – 7913
Helixi800 – 8023
Turni806 – 8116
Helixi818 – 8247
Helixi828 – 8303
Beta strandi859 – 86810
Beta strandi871 – 8777
Beta strandi879 – 8813
Beta strandi885 – 8895
Beta strandi905 – 9084
Helixi911 – 9144
Helixi920 – 9256
Helixi928 – 9303
Helixi935 – 9406
Beta strandi944 – 9485
Helixi950 – 9523

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IXDNMR-A460-550[»]
1WHLNMR-A125-206[»]
1WHMNMR-A228-304[»]
2VHFX-ray2.80A/B583-956[»]
ProteinModelPortaliQ9NQC7.
SMRiQ9NQC7. Positions 125-206, 228-307, 457-550, 583-956.

Miscellaneous databases

EvolutionaryTraceiQ9NQC7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini153 – 19846CAP-Gly 1Add
BLAST
Domaini253 – 28634CAP-Gly 2Add
BLAST
Domaini492 – 53544CAP-Gly 3Add
BLAST
Domaini592 – 950359USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni106 – 593488Interaction with TRIPAdd
BLAST
Regioni394 – 46976Interaction with TRAF2Add
BLAST
Regioni470 – 55485Interaction with IKBKG/NEMOAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C19 family.
Contains 3 CAP-Gly domains.
Contains 1 USP domain.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG313578.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ9NQC7.
KOiK08601.
OrthoDBiEOG72ZCDM.
PhylomeDBiQ9NQC7.
TreeFamiTF318734.

Family and domain databases

Gene3Di2.30.30.190. 3 hits.
InterProiIPR000938. CAP-Gly_domain.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamiPF01302. CAP_GLY. 3 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NQC7-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI    50
QDRSVGHSRI PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL 100
LAITNCEERF SLFKNRNRLS KGLQIDVGCP VKVQLRSGEE KFPGVVRFRG 150
PLLAERTVSG IFFGVELLEE GRGQGFTDGV YQGKQLFQCD EDCGVFVALD 200
KLELIEDDDT ALESDYAGPG DTMQVELPPL EINSRVSLKV GETIESGTVI 250
FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAC VESTILLHIN 300
DIIPALSESV TQERRPPKLA FMSRGVGDKG SSSHNKPKAT GSTSDPGNRN 350
RSELFYTLNG SSVDSQPQSK SKNTWYIDEV AEDPAKSLTE ISTDFDRSSP 400
PLQPPPVNSL TTENRFHSLP FSLTKMPNTN GSIGHSPLSL SAQSVMEELN 450
TAPVQESPPL AMPPGNSHGL EVGSLAEVKE NPPFYGVIRW IGQPPGLNEV 500
LAGLELEDEC AGCTDGTFRG TRYFTCALKK ALFVKLKSCR PDSRFASLQP 550
VSNQIERCNS LAFGGYLSEV VEENTPPKME KEGLEIMIGK KKGIQGHYNS 600
CYLDSTLFCL FAFSSVLDTV LLRPKEKNDV EYYSETQELL RTEIVNPLRI 650
YGYVCATKIM KLRKILEKVE AASGFTSEEK DPEEFLNILF HHILRVEPLL 700
KIRSAGQKVQ DCYFYQIFME KNEKVGVPTI QQLLEWSFIN SNLKFAEAPS 750
CLIIQMPRFG KDFKLFKKIF PSLELNITDL LEDTPRQCRI CGGLAMYECR 800
ECYDDPDISA GKIKQFCKTC NTQVHLHPKR LNHKYNPVSL PKDLPDWDWR 850
HGCIPCQNME LFAVLCIETS HYVAFVKYGK DDSAWLFFDS MADRDGGQNG 900
FNIPQVTPCP EVGEYLKMSL EDLHSLDSRR IQGCARRLLC DAYMCMYQSP 950
TMSLYK 956
Length:956
Mass (Da):107,316
Last modified:October 1, 2000 - v1
Checksum:i01831F9A83424631
GO
Isoform 2 (identifier: Q9NQC7-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:953
Mass (Da):107,044
Checksum:i0CCB3D21E2FF8851
GO

Sequence cautioni

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti747 – 7471E → G in MFT1 and BRSS. 1 Publication
VAR_045967

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei305 – 3073Missing in isoform 2. VSP_011277

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ250014 mRNA. Translation: CAB93533.1.
AB020656 mRNA. Translation: BAA74872.2. Different initiation.
BC012342 mRNA. Translation: AAH12342.1.
AF161542 mRNA. Translation: AAF29029.1. Frameshift.
CCDSiCCDS42164.1. [Q9NQC7-2]
CCDS45482.1. [Q9NQC7-1]
RefSeqiNP_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]
UniGeneiHs.578973.

Genome annotation databases

EnsembliENST00000311559; ENSP00000308928; ENSG00000083799. [Q9NQC7-1]
ENST00000398568; ENSP00000381574; ENSG00000083799. [Q9NQC7-2]
ENST00000427738; ENSP00000392025; ENSG00000083799. [Q9NQC7-1]
ENST00000564326; ENSP00000454515; ENSG00000083799. [Q9NQC7-2]
ENST00000569418; ENSP00000457576; ENSG00000083799. [Q9NQC7-2]
GeneIDi1540.
KEGGihsa:1540.
UCSCiuc002egp.1. human. [Q9NQC7-1]
uc002egq.1. human. [Q9NQC7-2]

Polymorphism databases

DMDMi51316104.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ250014 mRNA. Translation: CAB93533.1 .
AB020656 mRNA. Translation: BAA74872.2 . Different initiation.
BC012342 mRNA. Translation: AAH12342.1 .
AF161542 mRNA. Translation: AAF29029.1 . Frameshift.
CCDSi CCDS42164.1. [Q9NQC7-2 ]
CCDS45482.1. [Q9NQC7-1 ]
RefSeqi NP_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 ]
UniGenei Hs.578973.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1IXD NMR - A 460-550 [» ]
1WHL NMR - A 125-206 [» ]
1WHM NMR - A 228-304 [» ]
2VHF X-ray 2.80 A/B 583-956 [» ]
ProteinModelPortali Q9NQC7.
SMRi Q9NQC7. Positions 125-206, 228-307, 457-550, 583-956.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107920. 40 interactions.
IntActi Q9NQC7. 23 interactions.
MINTi MINT-6804518.
STRINGi 9606.ENSP00000308928.

Protein family/group databases

MEROPSi C67.001.

PTM databases

PhosphoSitei Q9NQC7.

Polymorphism databases

DMDMi 51316104.

Proteomic databases

MaxQBi Q9NQC7.
PaxDbi Q9NQC7.
PRIDEi Q9NQC7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000311559 ; ENSP00000308928 ; ENSG00000083799 . [Q9NQC7-1 ]
ENST00000398568 ; ENSP00000381574 ; ENSG00000083799 . [Q9NQC7-2 ]
ENST00000427738 ; ENSP00000392025 ; ENSG00000083799 . [Q9NQC7-1 ]
ENST00000564326 ; ENSP00000454515 ; ENSG00000083799 . [Q9NQC7-2 ]
ENST00000569418 ; ENSP00000457576 ; ENSG00000083799 . [Q9NQC7-2 ]
GeneIDi 1540.
KEGGi hsa:1540.
UCSCi uc002egp.1. human. [Q9NQC7-1 ]
uc002egq.1. human. [Q9NQC7-2 ]

Organism-specific databases

CTDi 1540.
GeneCardsi GC16P050775.
HGNCi HGNC:2584. CYLD.
HPAi CAB011713.
HPA050095.
MIMi 132700. phenotype.
601606. phenotype.
605018. gene.
605041. phenotype.
neXtProti NX_Q9NQC7.
Orphaneti 211. Familial cylindromatosis.
867. Familial multiple trichoepithelioma.
PharmGKBi PA27084.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG313578.
HOGENOMi HOG000006796.
HOVERGENi HBG051281.
InParanoidi Q9NQC7.
KOi K08601.
OrthoDBi EOG72ZCDM.
PhylomeDBi Q9NQC7.
TreeFami TF318734.

Enzyme and pathway databases

Reactomei REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_75776. NOD1/2 Signaling Pathway.

Miscellaneous databases

EvolutionaryTracei Q9NQC7.
GeneWikii CYLD_(gene).
GenomeRNAii 1540.
NextBioi 6377.
PROi Q9NQC7.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9NQC7.
Bgeei Q9NQC7.
CleanExi HS_CYLD.
Genevestigatori Q9NQC7.

Family and domain databases

Gene3Di 2.30.30.190. 3 hits.
InterProi IPR000938. CAP-Gly_domain.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view ]
Pfami PF01302. CAP_GLY. 3 hits.
PF00443. UCH. 1 hit.
[Graphical view ]
SMARTi SM01052. CAP_GLY. 3 hits.
[Graphical view ]
SUPFAMi SSF74924. SSF74924. 3 hits.
PROSITEi PS00845. CAP_GLY_1. 1 hit.
PS50245. CAP_GLY_2. 2 hits.
PS00972. USP_1. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. Cited for: FUNCTION, MUTAGENESIS OF CYS-601, INTERACTION WITH PLK1, SUBCELLULAR LOCATION.
  12. 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. 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. 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.

Entry informationi

Entry nameiCYLD_HUMAN
AccessioniPrimary (citable) accession number: Q9NQC7
Secondary accession number(s): O94934
, Q7L3N6, Q96EH0, Q9NZX9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: October 1, 2000
Last modified: September 3, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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