P57716 · NICA_MOUSE
- ProteinNicastrin
- GeneNcstn
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids708 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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). 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.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameNicastrin
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP57716
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Cytoplasmic vesicle membrane ; Single-pass type I membrane protein
Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Topological domain | 28-668 | Lumenal | |||
Transmembrane | 669-689 | Helical | |||
Topological domain | 690-708 | Cytoplasmic | |||
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Full embryonic lethality. No embryos survive past 10.d dpc. At 9.5 dpc the embryos display a phenotype similar to that of Notch1-deficient mice, with defects in the development of the caudal part of the embryo and in somite segementation, defective vascular morphogenesis in the yolk sac, and patterning defects in the developing heart and neural tube. Assembly of the gamma-secretase complex and APP processing are disrupted.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 34 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Signal | 1-27 | ||||
Chain | PRO_0000019682 | 28-708 | Nicastrin | ||
Glycosylation | 44 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 49↔61 | ||||
Glycosylation | 54 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 128 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 139↔158 | ||||
Glycosylation | 186 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 194↔212 | ||||
Glycosylation | 203 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 229↔247 | ||||
Glycosylation | 263 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 386 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 434 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 463 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 505 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 529 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 561 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 572 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 579 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 585↔619 | ||||
Glycosylation | 593 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 611 | N-linked (GlcNAc...) asparagine | |||
Post-translational modification
N-glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Component of the gamma-secretase complex. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2 (PubMed:12716934).
Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Interacts with PSEN1 and PSEN2
Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Interacts with PSEN1 and PSEN2
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | IntAct | |
---|---|---|---|---|---|
BINARY | P57716 | Calr P14211 | 2 | EBI-998934, EBI-644340 | |
BINARY | P57716 | Syvn1 Q9DBY1 | 2 | EBI-998934, EBI-644384 |
Complex viewer
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length708
- Mass (Da)78,492
- Last updated2011-07-27 v3
- MD5 ChecksumBAF82D04E52BBCDA8CAE4A8749378F06
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D6RCJ2 | D6RCJ2_MOUSE | Ncstn | 62 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Sequence conflict | 527 | in Ref. 1; AAG11413 and 3; AAH19998 | |||
Sequence conflict | 666 | in Ref. 1; AAG11413 | |||
Sequence conflict | 678-680 | in Ref. 1; AAG11413 and 3; AAH19998 | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF240469 EMBL· GenBank· DDBJ | AAG11413.1 EMBL· GenBank· DDBJ | mRNA | ||
AC158930 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC019998 EMBL· GenBank· DDBJ | AAH19998.1 EMBL· GenBank· DDBJ | mRNA |