CYLD
entrez
1540
canonical
uniprot
Q9NQC7
canonical
ensembl
ENSG00000083799
resolver
ensp
ENSP00000308928
resolver
ensp
ENSP00000381574
resolver
ensp
ENSP00000392025
resolver
ensp
ENSP00000454515
resolver
ensp
ENSP00000456488
resolver
ensp
ENSP00000457576
resolver
ensp
ENSP00000542894
resolver
ensp
ENSP00000542895
resolver
ensp
ENSP00000542896
resolver
ensp
ENSP00000542900
resolver
ensp
ENSP00000542905
resolver
ensp
ENSP00000542908
resolver
ensp
ENSP00000542909
resolver
ensp
ENSP00000542913
resolver
ensp
ENSP00000542914
resolver
ensp
ENSP00000590671
resolver
ensp
ENSP00000590672
resolver
ensp
ENSP00000637742
resolver
ensp
ENSP00000637747
resolver
ensp
ENSP00000646731
resolver
ensp
ENSP00000793369
resolver
genesymbol
CYLD
resolver
genesymbol_syn
CYLD1
resolver
genesymbol_syn
KIAA0849
resolver
hgnc
HGNC:2584
resolver
uniprot
O94934
resolver
uniprot
Q7L3N6
resolver
uniprot
Q96EH0
resolver
uniprot
Q9NZX9
resolver
uniprot_entry
CYLD_HUMAN
resolver
uniprot_sec
O94934
resolver
uniprot_sec
Q7L3N6
resolver
uniprot_sec
Q96EH0
resolver
uniprot_sec
Q9NZX9
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by phosphorylation at serine residues. {ECO:0000269|PubMed:15870263}.
uniprot
proteins
amino_acid_sequence
MSSGLWSQEKVTSPYWEERIFYLLLQECSVTDKQTQKLLKVPKGSIGQYIQDRSVGHSRIPSAKGKKNQIGLKILEQPHAVLFVDEKDVVEINEKFTELLLAITNCEERFSLFKNRNRLSKGLQIDVGCPVKVQLRSGEEKFPGVVRFRGPLLAERTVSGIFFGVELLEEGRGQGFTDGVYQGKQLFQCDEDCGVFVALDKLELIEDDDTALESDYAGPGDTMQVELPPLEINSRVSLKVGETIESGTVIFCDVLPGKESLGYFVGVDMDNPIGNWDGRFDGVQLCSFACVESTILLHINDIIPALSESVTQERRPPKLAFMSRGVGDKGSSSHNKPKATGSTSDPGNRNRSELFYTLNGSSVDSQPQSKSKNTWYIDEVAEDPAKSLTEISTDFDRSSPPLQPPPVNSLTTENRFHSLPFSLTKMPNTNGSIGHSPLSLSAQSVMEELNTAPVQESPPLAMPPGNSHGLEVGSLAEVKENPPFYGVIRWIGQPPGLNEVLAGLELEDECAGCTDGTFRGTRYFTCALKKALFVKLKSCRPDSRFASLQPVSNQIERCNSLAFGGYLSEVVEENTPPKMEKEGLEIMIGKKKGIQGHYNSCYLDSTLFCLFAFSSVLDTVLLRPKEKNDVEYYSETQELLRTEIVNPLRIYGYVCATKIMKLRKILEKVEAASGFTSEEKDPEEFLNILFHHILRVEPLLKIRSAGQKVQDCYFYQIFMEKNEKVGVPTIQQLLEWSFINSNLKFAEAPSCLIIQMPRFGKDFKLFKKIFPSLELNITDLLEDTPRQCRICGGLAMYECRECYDDPDISAGKIKQFCKTCNTQVHLHPKRLNHKYNPVSLPKDLPDWDWRHGCIPCQNMELFAVLCIETSHYVAFVKYGKDDSAWLFFDSMADRDGGQNGFNIPQVTPCPEVGEYLKMSLEDLHSLDSRRIQGCARRLLCDAYMCMYQSPTMSLYK
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:12190880, ECO:0000269|PubMed:16922728}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Trichoepithelioma, multiple familial, 1 (MFT1) [MIM:601606]: An 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. {ECO:0000269|PubMed:14632188, ECO:0000269|PubMed:16307661, ECO:0000269|PubMed:16922728}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:12190880, ECO:0000269|PubMed:12950348, ECO:0000269|PubMed:14632188, ECO:0000269|PubMed:15854031}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 8 (FTDALS8) [MIM:619132]: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS8 is an autosomal dominant form. {ECO:0000269|PubMed:23338750, ECO:0000269|PubMed:32185393, ECO:0000269|PubMed:32666117}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.19.12
uniprot
proteins
function
FUNCTION: Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-induced necroptosis (PubMed:18313383, PubMed:18636086, PubMed:19481526, PubMed:26670046, PubMed:26997266, PubMed:27458237, PubMed:27591049, PubMed:27746020, PubMed:29291351, PubMed:32185393). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:12917689, PubMed:12917691, PubMed:19481526, PubMed:32185393). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (PubMed:12917690). Negative regulator of Wnt signaling (PubMed:20227366). Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules (PubMed:19893491). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (PubMed:18222923, PubMed:20194890). Required for normal cell cycle progress and normal cytokinesis (PubMed:17495026, PubMed:19893491). Inhibits nuclear translocation of NF-kappa-B (PubMed:18636086). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (PubMed:18636086). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (By similarity). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (By similarity). Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins (PubMed:26670046, PubMed:26997266, PubMed:27458237, PubMed:27591049). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (PubMed:26997266). Involved in TNF-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (By similarity). Negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chain of NLRP6, thereby reducing the interaction between NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome (By similarity). Does not catalyze deubiquitination of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains (PubMed:27746020). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:29291351). Also removes 'Lys-63'-linked polyubiquitin chains of MAP3K1 and MA3P3K3, which inhibit their interaction with MAP2K1 and MAP2K2 (PubMed:34497368). {ECO:0000250|UniProtKB:Q80TQ2, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:12917690, ECO:0000269|PubMed:12917691, ECO:0000269|PubMed:17495026, ECO:0000269|PubMed:18222923, ECO:0000269|PubMed:18313383, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19481526, ECO:0000269|PubMed:19893491, ECO:0000269|PubMed:20194890, ECO:0000269|PubMed:20227366, ECO:0000269|PubMed:26670046, ECO:0000269|PubMed:26997266, ECO:0000269|PubMed:27458237, ECO:0000269|PubMed:27591049, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:29291351, ECO:0000269|PubMed:32185393, ECO:0000269|PubMed:34497368}.
uniprot
proteins
mass_dalton
107316
uniprot
proteins
mutagenesis
MUTAGEN 418; /note="S->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. Abolished phosphorylation by IKKE/IKBKE."; /evidence="ECO:0000269|PubMed:15870263, ECO:0000269|PubMed:19481526"; MUTAGEN 418; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-422; E-432; E-436; E-439; E-441 and E-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 422; /note="S->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."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 422; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-432; E-436; E-439; E-441 and E-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 432; /note="S->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."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 432; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-436; E-439; E-441 and E-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 436; /note="S->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."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 436; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-439; E-441 and E-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 439; /note="S->A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-441 and A-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 439; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-441 and E-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 441; /note="S->A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 441; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-444."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 444; /note="S->A: Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-441."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 444; /note="S->E: Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-441."; /evidence="ECO:0000269|PubMed:15870263"; MUTAGEN 457; /note="S->A: Abolishes binding to TRAF2."; /evidence="ECO:0000269|PubMed:12917691"; MUTAGEN 601; /note="C->A,S: Loss of deubiquitinating activity."; /evidence="ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:12917690, ECO:0000269|PubMed:17495026, ECO:0000269|PubMed:18313383, ECO:0000269|PubMed:27458237"; MUTAGEN 622; /note="L->D: Impaired interaction with SPATA2."; /evidence="ECO:0000269|PubMed:27591049"; MUTAGEN 871; /note="H->N: Loss of deubiquitinating activity."; /evidence="ECO:0000269|PubMed:12917691
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated. Polyubiquitinated in hepatocytes treated with palmitic acid. Ubiquitination is mediated by E3 ligase TRIM47 and leads to proteasomal degradation. {ECO:0000269|PubMed:29291351}.; PTM: Phosphorylated on several serine residues by IKKA and/or IKKB in response to immune stimuli (PubMed:15870263). Phosphorylation requires IKBKG (PubMed:15870263). Phosphorylation abolishes TRAF2 deubiquitination, interferes with the activation of Jun kinases, and strongly reduces CD40-dependent gene activation by NF-kappa-B (PubMed:15870263). Phosphorylation at Ser-418 by IKKE/IKBKE inhibits the deubiquitinase activity, leading to activation by NF-kappa-B (PubMed:19481526). {ECO:0000269|PubMed:15870263, ECO:0000269|PubMed:19481526}.
uniprot
proteins
protein_family
Peptidase C19 family
uniprot
proteins
pubmed
10048485
uniprot
proteins
pubmed
10835629
uniprot
proteins
pubmed
11042152
uniprot
proteins
pubmed
12168954
uniprot
proteins
pubmed
12190880
uniprot
proteins
pubmed
12917689
uniprot
proteins
pubmed
12917690
uniprot
proteins
pubmed
12917691
uniprot
proteins
pubmed
12950348
uniprot
proteins
pubmed
14632188
uniprot
proteins
pubmed
14676304
uniprot
proteins
pubmed
15341735
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15854031
uniprot
proteins
pubmed
15870263
uniprot
proteins
pubmed
16307661
uniprot
proteins
pubmed
16922728
uniprot
proteins
pubmed
17495026
uniprot
proteins
pubmed
18222923
uniprot
proteins
pubmed
18313383
uniprot
proteins
pubmed
18636086
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19481526
uniprot
proteins
pubmed
19893491
uniprot
proteins
pubmed
20194890
uniprot
proteins
pubmed
20227366
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23338750
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25134987
uniprot
proteins
pubmed
26670046
uniprot
proteins
pubmed
26997266
uniprot
proteins
pubmed
27307491
uniprot
proteins
pubmed
27458237
uniprot
proteins
pubmed
27545878
uniprot
proteins
pubmed
27591049
uniprot
proteins
pubmed
27746020
uniprot
proteins
pubmed
29291351
uniprot
proteins
pubmed
32185393
uniprot
proteins
pubmed
32666117
uniprot
proteins
pubmed
34497368
uniprot
proteins
sequence_length
956
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18313383, ECO:0000269|PubMed:32185393}. Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:25134987}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:25134987}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q80TQ2}. Note=Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase. During metaphase, it remains localized to the centrosome but is also present along the spindle (PubMed:25134987). {ECO:0000250|UniProtKB:Q80TQ2, ECO:0000269|PubMed:25134987}.
uniprot
proteins