Tchem NOTCH3 Neurogenic locus notch homolog protein 3

Protein Summary

Description

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9UM47
• Q9UEB3
• Q9UPL3
• Q9Y6L8
• Notch 3

Gene Name

• NOTCH3

Ensembl ID

• ENST00000263388
• ENSP00000263388
• ENSG00000074181

Symbol

• IMF2
• LMNS
• CASIL
• CADASIL
• CADASIL1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
biological term	0.98
disease perturbation	0.93
cell type or tissue	0.81
PubMedID	0.8

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 848.79   (req: < 5)

Gene RIFs: 305   (req: <= 3)

Antibodies: 655   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 848.79   (req: >= 5)

Gene RIFs: 305   (req: > 3)

Antibodies: 655   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 54

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (54)

Explore Active Ligands

1 – 10 of 54

CHEMBL3913200

NOTCH3Tchem

IC50: 8.43

CHEMBL3960841

NOTCH3Tchem

IC50: 8.38

CHEMBL3410161

NOTCH3Tchem

IC50: 8.4

CHEMBL3410156

NOTCH3Tchem

IC50: 6.79

CHEMBL3410158

NOTCH3Tchem

IC50: 6.92

CHEMBL3410159

NOTCH3Tchem

IC50: 7.21

CHEMBL3410157

NOTCH3Tchem

IC50: 7.54

CHEMBL3410154

NOTCH3Tchem

IC50: 7.62

CHEMBL3971963

NOTCH3Tchem

IC50: 8.52

CHEMBL3410166

NOTCH3Tchem

IC50: 8.22

Protein Data Bank (3)

1 – 3 of 3

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (47)

Reactome (18)

KEGG (9)

PathwayCommons (12)

WikiPathways (8)

Defective LFNG causes SCDO3 (R-HSA-5083630)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 18

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Defective LFNG causes SCDO3	5 targets	R-HSA-5083630
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases associated with O-glycosylation of proteins	71 targets	R-HSA-3906995
Reactome	Diseases of glycosylation	146 targets	R-HSA-3781865
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160

Name	Explore in Pharos	Explore in Source
Defective LFNG causes SCDO3	5 targets	R-HSA-5083630
Disease	1105 targets	R-HSA-1643685
Diseases associated with O-glycosylation of proteins	71 targets	R-HSA-3906995
Diseases of glycosylation	146 targets	R-HSA-3781865
Gene expression (Transcription)	1452 targets	R-HSA-74160

Gene Ontology Terms (25)

Functions (5)

Components (9)

Processes (11)

Find Similar Targets

Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
signaling receptor activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
cadherin binding	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
calcium ion binding	Inferred from Electronic Annotation (IEA)	InterPro
enzyme binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (208)

Explore Interacting Targets

1 – 10 of 208

• See Interactions on String-DB

HIF1AN

Tbio

Novelty: 0.01079184

p_int: 0.999999305

p_ni: 6.95e-7

p_wrong: 1e-9

Score: 0.375

Data Source: BioPlex,STRINGDB

ANKRD44

Tdark

Family: Enzyme

Novelty: 0.9

p_int: 0.999915535

p_ni: 0.000084458

p_wrong: 7e-9

Score: 0.347

Data Source: BioPlex,STRINGDB

PPP1R12B

Tbio

Family: Enzyme

Novelty: 0.06135268

p_int: 0.994802865

p_ni: 0.005197131

p_wrong: 4e-9

Score: 0.176

Data Source: BioPlex,STRINGDB

RBPJ

Tbio

Family: TF

Novelty: 0.00198074

p_int: 0.994284286

p_ni: 0.005715431

p_wrong: 2.83e-7

Score: 0.995

Data Source: BioPlex,Reactome,STRINGDB

DLK2

Tbio

Novelty: 0.14332684

p_int: 0.992306434

p_ni: 0.007692187

p_wrong: 0.000001379

Score: 0.189

Data Source: BioPlex,STRINGDB

ADAM33

Tchem

Family: Enzyme

Novelty: 0.00627958

p_int: 0.987737007

p_ni: 0.012262985

p_wrong: 8e-9

Score: 0.224

Data Source: BioPlex,STRINGDB

ADAM32

Tdark

Family: Enzyme

Novelty: 0.57613169

p_int: 0.982284194

p_ni: 0.017715798

p_wrong: 8e-9

Score: 0.174

Data Source: BioPlex,STRINGDB

DNAJC10

Tbio

Novelty: 0.04696061

p_int: 0.982284194

p_ni: 0.017715798

p_wrong: 8e-9

Data Source: BioPlex

RXFP1

Tchem

Family: GPCR

Novelty: 0.00590091

p_int: 0.977606611

p_ni: 0.022305342

p_wrong: 0.000088047

Data Source: BioPlex

ZNF408

Tbio

Family: TF

Novelty: 0.17075484

p_int: 0.968713905

p_ni: 0.031285885

p_wrong: 2.1e-7

Data Source: BioPlex

Publication Statistics

PubMed Score  848.79

PubMed score by year

Reset Zoom

PubTator Score  776.74

PubTator score by year

Reset Zoom

Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

ProtVista Viewer

Find similar targets by:

UniProt Keyword Find Similar Targets

3D-structure
Activator
ANK repeat
Cell membrane
Complete proteome
Developmental protein
Differentiation
Disease mutation
Disulfide bond
EGF-like domain

GWAS Trait Find Similar Targets

platelet crit

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype