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nicastrin (human)

Overview nicastrin 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 (beta- amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist. Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Constitutively expressed in neural cells. Widely expressed. Belongs to the nicastrin family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB. Protein type: Membrane protein, integral Cellular Component: Golgi apparatus; integral to plasma membrane; endoplasmic reticulum; lysosomal membrane; melanosome; plasma membrane; integral to membrane Molecular Function: protein binding; endopeptidase activity Biological Process: positive regulation of catalytic activity; Notch signaling pathway; membrane protein intracellular domain proteolysis; nerve growth factor receptor signaling pathway; apoptosis; myeloid cell homeostasis; membrane protein ectodomain proteolysis; Notch receptor processing; proteolysis; T cell proliferation; epithelial cell proliferation; amyloid precursor protein catabolic process; beta-amyloid metabolic process; protein processing Reference #:  Q92542 (UniProtKB) Alt. Names/Synonyms: anterior pharynx-defective 2; APH2; ATAG1874; KIAA0253; NCSTN; NICA; Nicastrin Gene Symbols: NCSTN Molecular weight: 78,411 Da Basal Isoelectric point: 5.67  Predict pI for various phosphorylation states CST Pathways:  Alzheimer's Disease  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  Notch Signaling Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below nicastrin

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	Sites Implicated In
molecular association, regulation: S437‑p protein degradation: S437‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		K110-a	FTRDLMEkLkGRTSR
0	1		K112-a	RDLMEkLkGRTSRIA
0	1		S241	SSIQSTFSINPEIVC
0	1		K349-a	RMVYDMEkGkFPVQL
0	7		K351-u	VYDMEkGkFPVQLEN
0	6		K403-u	DLLATLEkSGAGVPA
0	1		S425-p	QSQPLPPssLQRFLR
0	1		S426-p	SQPLPPssLQRFLRA
0	1		R434-m1	LQRFLRArNIsGVVL
1	0		S437-p	FLRArNIsGVVLADH
0	2		T672-p	SKELELItLtVGFGI
0	2		T674-p	ELELItLtVGFGILI

	mouse
K109	FTRDVMEKLKGTTSR
K111	RDVMEKLKGTTSRIA
S240-p	SFIQSTFsINPEIVC
N348	RMVYDMENGKFPVRL
K350	VYDMENGKFPVRLEN
K402	DLLATLEKSGAGVPE
S424	QSQALPPSSLQRFLR
S425	SQALPPSSLQRFLRA
R433	LQRFLRARNISGVVL
S436	FLRARNISGVVLADH
T671	SKELEFITLIVGFST
I673	ELEFITLIVGFSTLV

	rat
K109	FTRDIMEKLKGETSR
K111	RDIMEKLKGETSRIA
S240	SFIQSTFSINPEIVC
N348	RMVYDMENGKFPVRL
K350	VYDMENGKFPVRLEN
Q402	DLLVTLEQSGADTPQ
S424	QSQALPPSSLQRFLR
S425	SQALPPSSLQRFLRA
R433	LQRFLRARNISGVVL
S436	FLRARNISGVVLADH
T671	SKELEFITLIVGFSI
I673	ELEFITLIVGFSILV

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