NCSTN

Protein identityUniProt · HPA

UniProt accession

Q92542

Gene

NCSTN

Ensembl

ENSG00000162736

Chromosome

1

Canonical length

709 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

709 residues, UniProt reviewed canonical sequence.

>Q92542|NCSTN
     1  MATAGGGSGA DPGSRGLLRL LSFCVLLAGL CRGNSVERKI YIPLNKTAPC VRLLNATHQI
    61  GCQSSISGDT GVIHVVEKEE DLQWVLTDGP NPPYMVLLES KHFTRDLMEK LKGRTSRIAG
   121  LAVSLTKPSP ASGFSPSVQC PNDGFGVYSN SYGPEFAHCR EIQWNSLGNG LAYEDFSFPI
   181  FLLEDENETK VIKQCYQDHN LSQNGSAPTF PLCAMQLFSH MHAVISTATC MRRSSIQSTF
   241  SINPEIVCDP LSDYNVWSML KPINTTGTLK PDDRVVVAAT RLDSRSFFWN VAPGAESAVA
   301  SFVTQLAAAE ALQKAPDVTT LPRNVMFVFF QGETFDYIGS SRMVYDMEKG KFPVQLENVD
   361  SFVELGQVAL RTSLELWMHT DPVSQKNESV RNQVEDLLAT LEKSGAGVPA VILRRPNQSQ
   421  PLPPSSLQRF LRARNISGVV LADHSGAFHN KYYQSIYDTA ENINVSYPEW LSPEEDLNFV
   481  TDTAKALADV ATVLGRALYE LAGGTNFSDT VQADPQTVTR LLYGFLIKAN NSWFQSILRQ
   541  DLRSYLGDGP LQHYIAVSSP TNTTYVVQYA LANLTGTVVN LTREQCQDPS KVPSENKDLY
   601  EYSWVQGPLH SNETDRLPRC VRSTARLARA LSPAFELSQW SSTEYSTWTE SRWKDIRARI
   661  FLIASKELEL ITLTVGFGIL IFSLIVTYCI NAKADVLFIA PREPGAVSY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NCSTN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

85 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NCSTN.

Disease | AllUniProt

Conditions NCSTN is implicated in, by any mechanism.

• Acne inversa, familial, 1 (ACNINV1) MIM:142690

Disease | GeneticClinVar

23 pathogenic / likely-pathogenic of 573 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Acne inversa, familial, 1
• Abnormality of the skin

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.23

gnomAD pLI

1

gnomAD missense Z

1.43

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 15% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult behavior
• amyloid precursor protein catabolic process
• amyloid precursor protein metabolic process
• amyloid-beta formation
• cellular response to calcium ion
• central nervous system myelination
• cerebellum development
• epithelial cell proliferation
• G protein-coupled dopamine receptor signaling pathway
• glutamate receptor signaling pathway
• learning or memory
• membrane protein ectodomain proteolysis
• membrane protein intracellular domain proteolysis
• myeloid cell homeostasis
• neuron apoptotic process
• Notch receptor processing
• Notch signaling pathway
• positive regulation of amyloid precursor protein biosynthetic process
• protein processing
• proteolysis
• regulation of long-term synaptic potentiation
• short-term synaptic potentiation
• T cell proliferation
• amyloid precursor protein biosynthetic process

Molecular functions

• aspartic endopeptidase activity, intramembrane cleaving
• ATPase binding
• endopeptidase activator activity
• growth factor receptor binding
• protein-macromolecule adaptor activity

Cellular components

• azurophil granule membrane
• early endosome
• endoplasmic reticulum
• endoplasmic reticulum membrane
• endosome membrane
• extracellular exosome
• focal adhesion
• gamma-secretase complex
• Golgi apparatus
• Golgi membrane
• lysosomal membrane
• melanosome
• membrane
• plasma membrane
• presynaptic membrane
• sarcolemma
• synaptic vesicle

Protein domainsUniProt · Pfam · InterPro

• Nicastrin
• Nicastrin, small lobe
• Nicastrin large lobe
• Nicastrin small lobe

KeywordsUniProt

• Cytoplasmic vesicle
• Disulfide bond
• Glycoprotein
• Membrane
• Notch signaling pathway
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NCSTN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PSEN1
• PSEN2
• OSTC
• KRTCAP2
• APH1A
• CANX
• PSENEN