Nicastrin Antibody [H21H1] | Primary Antibodies

Application: Reactivity: Human, Mouse, Rat, Monkey

Lane 1: Hela, Lane 2: 3T3, Lane 3: C6, Lane 4: COS-7

Usage Information

Dilution
WB1:1000 IP1:50 IF1:200

Application
WB, IP, IF

Reactivity
Human, Mouse, Rat, Monkey

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
110 kDa, 120 kDa

Positive Control	Mouse cerebellum; Mouse retina; Mouse liver; Mouse small intestine; HeLa cells; 3T3 cells; C6 cells; COS-7 cells
Negative Control

Datasheet & SDS

Biological Description

Specificity
Nicastrin Antibody [H21H1] detects endogenous levels of total Nicastrin protein.

Clone
H21H1

Synonym(s)
NCSTN; Nicastrin; KIAA0253; UNQ1874/PRO4317

Background
Nicastrin is an essential type I transmembrane glycoprotein and a core subunit of the γ-secretase complex, acting as the substrate receptor that recognizes and presents ectodomain-shed stubs of proteins like APP and Notch for intramembrane cleavage, which generates signaling peptides such as amyloid-β and the Notch intracellular domain implicated in Alzheimer's disease and developmental processes. It features a large, heavily glycosylated extracellular domain with a central β-sandwich core stabilized by disulfide bonds, a dynamic N-terminal lobe containing a substrate-binding pocket (including key residues in the DYIGS motif that capture free N-termini after ectodomain shedding), a single C-terminal transmembrane helix that interacts with presenilin, Aph1, and Pen2 to form the horseshoe-shaped γ-secretase complex, and a short cytoplasmic tail. The extracellular domain of nicastrin binds short hydrophilic N-terminal stubs of substrates through electrostatic interactions, positioning their transmembrane segments precisely above presenilin's catalytic aspartate residues for sequential γ-cleavage, while also stabilizing complex assembly and directing its trafficking to plasma and endosomal membranes. Mutations that disrupt the extracellular binding pocket can abolish substrate recognition without affecting complex formation.

Background

Nicastrin is an essential type I transmembrane glycoprotein and a core subunit of the γ-secretase complex, acting as the substrate receptor that recognizes and presents ectodomain-shed stubs of proteins like APP and Notch for intramembrane cleavage, which generates signaling peptides such as amyloid-β and the Notch intracellular domain implicated in Alzheimer's disease and developmental processes. It features a large, heavily glycosylated extracellular domain with a central β-sandwich core stabilized by disulfide bonds, a dynamic N-terminal lobe containing a substrate-binding pocket (including key residues in the DYIGS motif that capture free N-termini after ectodomain shedding), a single C-terminal transmembrane helix that interacts with presenilin, Aph1, and Pen2 to form the horseshoe-shaped γ-secretase complex, and a short cytoplasmic tail. The extracellular domain of nicastrin binds short hydrophilic N-terminal stubs of substrates through electrostatic interactions, positioning their transmembrane segments precisely above presenilin's catalytic aspartate residues for sequential γ-cleavage, while also stabilizing complex assembly and directing its trafficking to plasma and endosomal membranes. Mutations that disrupt the extracellular binding pocket can abolish substrate recognition without affecting complex formation.

References
https://pubmed.ncbi.nlm.nih.gov/16096062/ https://pubmed.ncbi.nlm.nih.gov/25565961/

Reference Table for Selecting PVDF Membrane Pore Size Specifications

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%