PMADS

Id:	acc1900
Group:	2sens
Protein:	CUL4A
Gene Symbol:	CUL4A
Protein Id:	Q13619
Protein Name:	CUL4A_HUMAN
PTM:	neddylation
Site:	unclear
Site Sequence:
Disease Category:	Cancer
Disease:	Lung Cancer
Disease Subtype:
Disease Cellline:	H1299?
Disease Info:
Drug:	MLN4924
Drug Info:	"MLN4924 (Pevonedistat) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor with an IC50 of 4.7 nM, primarily investigated for its anticancer activity by blocking cullin-RING ubiquitin ligase (CRL)-mediated protein degradation."
Effect:	resist
Effect Info:	Knockout of UBC12 inhibits the neddylation of Cullin and suppresses the growth of lung cancer cells resistant to MLN4924.
Note:
Score:	5.0
Pubmed(PMID):	31208947
Sentence Index:	31208947_13-14
Sentence:	"Further mechanistical studies revealed that UBC12 knockdown inhibited Cullin neddylation, led to the inactivation of CRL E3 ligases and induced the accumulation of tumor-suppressive CRL substrates (p21, p27 and Wee1) to induce cell cycle arrest and suppress the malignant phenotypes of lung cancer cells. Finally, UBC12 knockdown effectively inhibited the growth of MLN4924-resistant lung cancer cells."

Sequence & Structure:

MADEAPRKGSFSALVGRTNGLTKPAALAAAPAKPGGAGGSKKLVIKNFRDRPRLPDNYTQDTWRKLHEAVRAVQSSTSIRYNLEELYQAVENLCSHKVSPMLYKQLRQACEDHVQAQILPFREDSLDSVLFLKKINTCWQDHCRQMIMIRSIFLFLDRTYVLQNSTLPSIWDMGLELFRTHIISDKMVQSKTIDGILLLIERERSGEAVDRSLLRSLLGMLSDLQVYKDSFELKFLEETNCLYAAEGQRLMQEREVPEYLNHVSKRLEEEGDRVITYLDHSTQKPLIACVEKQLLGEHLTAILQKGLDHLLDENRVPDLAQMYQLFSRVRGGQQALLQHWSEYIKTFGTAIVINPEKDKDMVQDLLDFKDKVDHVIEVCFQKNERFVNLMKESFETFINKRPNKPAELIAKHVDSKLRAGNKEATDEELERTLDKIMILFRFIHGKDVFEAFYKKDLAKRLLVGKSASVDAEKSMLSKLKHECGAAFTSKLEGMFKDMELSKDIMVHFKQHMQNQSDSGPIDLTVNILTMGYWPTYTPMEVHLTPEMIKLQEVFKAFYLGKHSGRKLQWQTTLGHAVLKAEFKEGKKEFQVSLFQTLVLLMFNEGDGFSFEEIKMATGIEDSELRRTLQSLACGKARVLIKSPKGKEVEDGDKFIFNGEFKHKLFRIKINQIQMKETVEEQVSTTERVFQDRQYQIDAAIVRIMKMRKTLGHNLLVSELYNQLKFPVKPGDLKKRIESLIDRDYMERDKDNPNQYHYVA

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	myelodysplastic syndrome	EMA DailyMed
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Not yet recruiting	myelodysplastic syndrome	ClinicalTrials
CUL4A	POMALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	immune system disease	ATC
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	immune system disease	ATC
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	immune system disease	ATC
CUL4A	POMALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	multiple myeloma	EMA DailyMed
CUL4A	POMALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Not yet recruiting	multiple myeloma	ClinicalTrials
CUL4A	POMALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Withdrawn	multiple myeloma	ClinicalTrials
CUL4A	POMALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Recruiting	multiple myeloma	ClinicalTrials
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	multiple myeloma	DailyMed EMA
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Completed	multiple myeloma	ClinicalTrials
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Unknown status	multiple myeloma	ClinicalTrials ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	multiple myeloma	DailyMed EMA
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Active, not recruiting	multiple myeloma	ClinicalTrials ClinicalTrials ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Completed	multiple myeloma	ClinicalTrials ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Recruiting	multiple myeloma	ClinicalTrials ClinicalTrials ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	Withdrawn	multiple myeloma	ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	Mantle cell lymphoma	EMA DailyMed
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	4	-	anemia	DailyMed
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	3	Unknown status	hepatocellular carcinoma	ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	3	Completed	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials ClinicalTrials
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	3	Terminated	hepatocellular carcinoma	ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	3	Completed	myelodysplastic syndrome	ClinicalTrials ClinicalTrials
CUL4A	THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	3	Completed	myelodysplastic syndrome	ClinicalTrials
CUL4A	LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase inhibitor	3	Active, not recruiting	myelodysplastic syndrome	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

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 data.

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