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Protein Page:
nicastrin (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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; lysosomal membrane; endoplasmic reticulum; integral to membrane; melanosome; plasma membrane
Molecular Function: protein binding; endopeptidase activity
Biological Process: positive regulation of catalytic activity; Notch signaling pathway; extracellular matrix organization and biogenesis; membrane protein intracellular domain proteolysis; nerve growth factor receptor signaling pathway; positive regulation of apoptosis; membrane protein ectodomain proteolysis; myeloid cell homeostasis; Notch receptor processing; proteolysis; T cell proliferation; extracellular matrix disassembly; 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® Total Proteins
Select Structure to View Below

nicastrin

Protein Structure Not Found.


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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
 

Show Multiple Sequence Alignment


 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-ac FTRDLMEkLkGRTSR
0 1 K112-ac RDLMEkLkGRTSRIA
0 1 S241 SSIQSTFSINPEIVC
0 1 K349-ac RMVYDMEkGkFPVQL
0 7 K351-ub VYDMEkGkFPVQLEN
0 6 K403-ub DLLATLEkSGAGVPA
0 1 S425-p QSQPLPPssLQRFLR
0 1 S426-p SQPLPPssLQRFLRA
0 1 R434-m1 LQRFLRArNIsGVVL
1 0 S437-p FLRArNIsGVVLADH
0 1 S638-p LSPAFELsQWSSTEY
0 1 T647-p WSSTEYStWtESRWK
0 1 T649-p STEYStWtESRWKDI
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
S637 LSPAFELSQWSSTEY
T646 WSSTEYSTWAESRWK
A648 STEYSTWAESRWKDI
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
S637 LSPAFELSQWSSTEY
T646 WSSTEYSTWAESRWK
A648 STEYSTWAESRWKDI
T671 SKELEFITLIVGFSI
I673 ELEFITLIVGFSILV
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