PMADS

Id:	acc2419
Group:	2sens
Protein:	CYLD
Gene Symbol:	CYLD
Protein Id:	Q9NQC7
Protein Name:	CYLD_HUMAN
PTM:	phosphorylation
Site:	Ser418
Site Sequence:	SLTTENRFHSLPFSLTKMPNT
Disease Category:	Cancer
Disease:	Leukemia
Disease Subtype:	Adult T-cell leukemia/lymphoma
Disease Cellline:	MT4
Disease Info:
Drug:	birinapant
Drug Info:	"Birinapant is a second mitochondrial-derived activator of caspases (SMAC) mimetic and inhibitor of apoptosis (IAP) antagonist that promotes cancer cell death by targeting IAP proteins, currently under clinical evaluation for the treatment of hematologic malignancies and solid tumors."
Effect:	modulate
Effect Info:	"SMAC mimetics or IKK inhibitors can also disrupt the phosphorylation of CYLD and induce the death of ATLL cells by reducing the ubiquitination of RIPK1, which is CYLD-dependent."
Note:
Score:	4.0
Pubmed(PMID):	32024820
Sentence Index:	32024820_13-14
Sentence:	"In the absence of CYLD, RIPK1 ubiquitination remains elevated following IKK blockade and it does not associate with the DISC. SMAC mimetics can similarly disrupt CYLD phosphorylation and lead to ATLL cell death through reduction of RIPK1 ubiquitination, which is CYLD dependent."

Sequence & Structure:

MSSGLWSQEKVTSPYWEERIFYLLLQECSVTDKQTQKLLKVPKGSIGQYIQDRSVGHSRIPSAKGKKNQIGLKILEQPHAVLFVDEKDVVEINEKFTELLLAITNCEERFSLFKNRNRLSKGLQIDVGCPVKVQLRSGEEKFPGVVRFRGPLLAERTVSGIFFGVELLEEGRGQGFTDGVYQGKQLFQCDEDCGVFVALDKLELIEDDDTALESDYAGPGDTMQVELPPLEINSRVSLKVGETIESGTVIFCDVLPGKESLGYFVGVDMDNPIGNWDGRFDGVQLCSFACVESTILLHINDIIPALSESVTQERRPPKLAFMSRGVGDKGSSSHNKPKATGSTSDPGNRNRSELFYTLNGSSVDSQPQSKSKNTWYIDEVAEDPAKSLTEISTDFDRSSPPLQPPPVNSLTTENRFHSLPFSLTKMPNTNGSIGHSPLSLSAQSVMEELNTAPVQESPPLAMPPGNSHGLEVGSLAEVKENPPFYGVIRWIGQPPGLNEVLAGLELEDECAGCTDGTFRGTRYFTCALKKALFVKLKSCRPDSRFASLQPVSNQIERCNSLAFGGYLSEVVEENTPPKMEKEGLEIMIGKKKGIQGHYNSCYLDSTLFCLFAFSSVLDTVLLRPKEKNDVEYYSETQELLRTEIVNPLRIYGYVCATKIMKLRKILEKVEAASGFTSEEKDPEEFLNILFHHILRVEPLLKIRSAGQKVQDCYFYQIFMEKNEKVGVPTIQQLLEWSFINSNLKFAEAPSCLIIQMPRFGKDFKLFKKIFPSLELNITDLLEDTPRQCRICGGLAMYECRECYDDPDISAGKIKQFCKTCNTQVHLHPKRLNHKYNPVSLPKDLPDWDWRHGCIPCQNMELFAVLCIETSHYVAFVKYGKDDSAWLFFDSMADRDGGQNGFNIPQVTPCPEVGEYLKMSLEDLHSLDSRRIQGCARRLLCDAYMCMYQSPTMSLYK

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

No data.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

CYLD-Ser341
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

CYLD-Ser358
Cancer	Intensity
BRCA
COAD	0.411
HGSC
ccRCC	0.723
GBM
HNSC
LUAD	0.346
LUSC
non_ccRCC
PDAC
UCEC	-1.48

CYLD-Ser359
Cancer	Intensity
BRCA	1.125
COAD	0.923
HGSC	-0.341
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC	-1.246
PDAC
UCEC	-0.461

CYLD-Ser362
Cancer	Intensity
BRCA
COAD
HGSC	-1.475
ccRCC	0.331
GBM
HNSC	1.296
LUAD	0.031
LUSC
non_ccRCC
PDAC
UCEC	-0.182

CYLD-Ser366
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-1.414
LUSC	0.122
non_ccRCC	0.921
PDAC
UCEC	0.371

CYLD-Ser384
Cancer	Intensity
BRCA	0.032
COAD
HGSC	-2.649
ccRCC	-0.097
GBM	-0.127
HNSC	0.762
LUAD	0.627
LUSC	0.72
non_ccRCC	0.479
PDAC	0.447
UCEC	-0.192

CYLD-Ser395
Cancer	Intensity
BRCA
COAD	0.333
HGSC	-1.124
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.791

CYLD-Ser396
Cancer	Intensity
BRCA	-0.611
COAD	0.666
HGSC	-1.356
ccRCC	0.15
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	1.15

CYLD-Ser406
Cancer	Intensity
BRCA
COAD	0.707
HGSC
ccRCC
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

CYLD-Ser415
Cancer	Intensity
BRCA	-1.406
COAD	-0.166
HGSC	2.624
ccRCC	-0.197
GBM	-0.067
HNSC	-0.794
LUAD	0.011
LUSC	0.201
non_ccRCC	0.333
PDAC	-0.536
UCEC	-0.003

CYLD-Ser419
Cancer	Intensity
BRCA	-0.105
COAD	-0.524
HGSC	-0.476
ccRCC	0.041
GBM	0.594
HNSC	-1.261
LUAD	0.144
LUSC	-0.15
non_ccRCC	2.656
PDAC	-0.353
UCEC	-0.566

CYLD-Ser544
Cancer	Intensity
BRCA	-0.225
COAD
HGSC	0.077
ccRCC	0.157
GBM	1.198
HNSC	-0.114
LUAD	-1.699
LUSC	-0.391
non_ccRCC	1.969
PDAC	-0.692
UCEC	-0.28

CYLD-Ser549
Cancer	Intensity
BRCA	-0.4
COAD	-0.164
HGSC	0.399
ccRCC	-0.005
GBM	-1.67
HNSC	1.342
LUAD	-0.55
LUSC	-1.005
non_ccRCC	1.098
PDAC	1.499
UCEC	-0.544

CYLD-Ser557
Cancer	Intensity
BRCA	0.69
COAD	0.328
HGSC	-2.601
ccRCC	-0.234
GBM	-0.781
HNSC	0.182
LUAD	0.366
LUSC	0.843
non_ccRCC	0.784
PDAC	0.661
UCEC	-0.238

CYLD-Ser565
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.151
GBM	-1.411
HNSC	0.32
LUAD	0.94
LUSC
non_ccRCC
PDAC
UCEC

CYLD-Ser836
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

CYLD-Tyr15
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

CYLD-Tyr563
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.165
GBM
HNSC	-0.908
LUAD	1.072
LUSC
non_ccRCC
PDAC
UCEC

CYLD-Tyr832
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

No data.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb