DegronMD - Q9NQC7(CYLD)

FUNCTION: Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis (PubMed:18636086, PubMed:26670046, PubMed:27458237, PubMed:26997266, PubMed:27591049, PubMed:29291351, PubMed:18313383, PubMed:32185393). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:12917689, PubMed:12917691, 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-alpha-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins (PubMed:26997266, PubMed:26670046, PubMed:27458237, PubMed:27591049). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (PubMed:26997266). Involved in TNF-alpha-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). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:29291351). {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: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:29291351, ECO:0000269|PubMed:32185393}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P482L	TCGA-BF-A5EQ	SKCM	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation altering degron motif	0.6471
p.P482L	DO219452	SKCM	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation altering degron motif	0.6471
p.G492S	TCGA-BR-8078	STAD	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.0556
p.G492S	DO38288	STAD	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.0556
p.E471D	TCGA-CD-8529	STAD	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.1389
p.E471D	DO47753	STAD	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.1389
p.P483H	TCGA-DA-A1IB	SKCM	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.3056
p.P483H	DO38033	SKCM	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.3056
p.A476V	TCGA-DU-6392	LGG	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.2778
p.A476V	DO22237	LGG	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.2778
p.E471Q	TCGA-EA-A3HU	CESC	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.1389
p.E471Q	DO6320	CESC	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.1389
p.E480K	TCGA-EB-A4IS	SKCM	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation altering degron motif	0.7022
p.E480K	DO47281	SKCM	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation altering degron motif	0.7022
p.H468P	TCGA-EO-A22R	UCEC	TCGA	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.0556
p.H468P	DO42713	UCEC	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.0556
p.L475V	DO233893	GACA	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.25
p.V472A	DO233865	GACA	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.1667
p.W490C	DO229045	LICA	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.1111
p.P483L	DO229479	SKCA	ICGC	VKENP	DEG_APCC_KENBOX_2	478:482	Mutation rewiring degron network	0.3056

DegronMD: protein-targeted degradation, mutation and drug response to degrons

CYLD

UniProt ID: Q9NQC7

Entrez ID: 1540

Protein name: Ubiquitin carboxyl-terminal hydrolase CYLD (EC 3.4.19.12) (Deubiquitinating enzyme CYLD) (Ubiquitin thioesterase CYLD) (Ubiquitin-specific-processing protease CYLD)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for CYLD in