Tbio NCSTN Nicastrin

Protein Summary

Description

Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]

Uniprot Accession IDs

• Q92542
• Q5T207
• Q5T208
• Q86VV5

Gene Name

• NCSTN

Ensembl ID

• ENST00000294785
• ENSP00000294785
• ENSG00000162736

Symbol

• KIAA0253
• ATAG1874

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	0.96
protein complex	0.94
histone modification site profile	0.86
cellular component	0.78
transcription factor perturbation	0.74

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: 147.87   (req: < 5)

Gene RIFs: 81   (req: <= 3)

Antibodies: 448   (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: 147.87   (req: >= 5)

Gene RIFs: 81   (req: > 3)

Antibodies: 448   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

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

Active Ligand: 0

Tclin

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

Active Drug: 0

Protein Data Bank (8)

1 – 5 of 8

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

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (51)

Reactome (37)

KEGG (2)

PathwayCommons (9)

WikiPathways (3)

Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)

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Items per page:

5

1 – 5 of 37

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activated NOTCH1 Transmits Signal to the Nucleus	31 targets	R-HSA-2122948
Reactome	Amyloid fiber formation	79 targets	R-HSA-977225
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Cell death signalling via NRAGE, NRIF and NADE	76 targets	R-HSA-204998
Reactome	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	58 targets	R-HSA-2894862

Name	Explore in Pharos	Explore in Source
Activated NOTCH1 Transmits Signal to the Nucleus	31 targets	R-HSA-2122948
Amyloid fiber formation	79 targets	R-HSA-977225
Axon guidance	533 targets	R-HSA-422475
Cell death signalling via NRAGE, NRIF and NADE	76 targets	R-HSA-204998
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	58 targets	R-HSA-2894862

Gene Ontology Terms (29)

Functions (1)

Components (15)

Processes (13)

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Items per page:

10

1 – 1 of 1

GO Term	Evidence	Assigned by
endopeptidase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Protein-Protein Interactions (177)

Explore Interacting Targets

1 – 10 of 177

• See Interactions on String-DB

ACTA1

Tbio

Novelty: 0.00147233

p_int: 0.999999871

p_ni: 1.29e-7

Score: 0.177

Data Source: BioPlex,STRINGDB

ALOX5

Tclin

Family: Enzyme

Novelty: 0.00071056

p_int: 0.999845316

p_ni: 0.000154684

Score: 0.334

Data Source: BioPlex,STRINGDB

MICAL1

Tbio

Family: Enzyme

Novelty: 0.01559445

p_int: 0.994293887

p_ni: 0.005658908

p_wrong: 0.000047205

Score: 0.175

Data Source: BioPlex,STRINGDB

RRAS

Tbio

Family: Enzyme

Novelty: 0.00229703

p_int: 0.982687581

p_ni: 0.016975526

p_wrong: 0.000336893

Score: 0.208

Data Source: BioPlex,STRINGDB

SRC

Tclin

Family: Kinase

Novelty: 0.00009742

p_int: 0.974903452

p_ni: 0.025094795

p_wrong: 0.000001753

Score: 0.205

Data Source: BioPlex,STRINGDB

PAG1

Tbio

Novelty: 0.0206299

p_int: 0.945469639

p_ni: 0.05451726

p_wrong: 0.000013101

Data Source: BioPlex

EEF1A2

Tchem

Novelty: 0.0002261

p_int: 0.914109812

p_ni: 0.085890188

Data Source: BioPlex

EEPD1

Tbio

Family: Enzyme

Novelty: 0.33802817

p_int: 0.904822289

p_ni: 0.08506369

p_wrong: 0.01011402

Score: 0.179

Data Source: BioPlex,STRINGDB

PTPRG

Tchem

Family: Enzyme

Novelty: 0.02045926

p_int: 0.893194732

p_ni: 0.106805267

p_wrong: 1e-9

Score: 0.15

Data Source: BioPlex,STRINGDB

VASN

Tbio

Novelty: 0.04337164

p_int: 0.883486142

p_ni: 0.116513858

Score: 0.416

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  147.87

PubMed score by year

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PubTator Score  84.75

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Complete proteome
Cytoplasmic vesicle
Disease mutation
Disulfide bond
Glycoprotein
Membrane
Notch signaling pathway
Polymorphism

GWAS Trait Find Similar Targets

multiple sclerosis

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
integument phenotype
mortality/aging