Nicastrin (NCSTN)
The protein contains 709 amino acids for an estimated molecular weight of 78411 Da.
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) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). 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. (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs12045198 | |
| dbSNP:rs35603924 | |
| ACNINV1 |
Biological Process
Adult behavior
Amyloid fibril formation
Amyloid precursor protein biosynthetic process
Amyloid precursor protein catabolic process
Amyloid precursor protein metabolic process
Amyloid-beta formation
Amyloid-beta metabolic process
Apoptotic signaling pathway
Axon guidance
Cellular protein metabolic process
Cellular response to calcium ion
Central nervous system myelination
Cerebellum development
Dopamine receptor signaling pathway
Ephrin receptor signaling pathway
Epithelial cell proliferation
Extracellular matrix disassembly
Extracellular matrix organization
Glutamate receptor signaling pathway
Learning or memory
Membrane protein ectodomain proteolysis
Membrane protein intracellular domain proteolysis
Myeloid cell homeostasis
Neuron apoptotic process
Neurotrophin TRK receptor signaling pathway
Neutrophil degranulation
Notch receptor processing
Notch receptor processing, ligand-dependent
Notch signaling pathway
Positive regulation of amyloid precursor protein biosynthetic process
Positive regulation of apoptotic process
Positive regulation of catalytic activity
Positive regulation of endopeptidase activity
Protein processing
Proteolysis
Regulation of long-term synaptic potentiation
Short-term synaptic potentiation
T cell proliferation
Cellular Component
Azurophil granule membrane
Early endosome
Endoplasmic reticulum
Endosome membrane
Extracellular exosome
Focal adhesion
Gamma-secretase complex
Golgi apparatus
Integral component of membrane
Integral component of plasma membrane
Integral component of presynaptic membrane
Lysosomal membrane
Melanosome
Membrane
Mitochondrion
Plasma membrane
Sarcolemma
Synaptic vesicle
The reference OMIM entry for this protein is 142690
Acne inversa, familial, 1; acninv1
Acne inversa, familial
Hidradenitis suppurativa, familial
A number sign (#) is used with this entry because familial acne inversa-1 (ACNINV1) is caused by haploinsufficiency for the gene encoding nicastrin (NCSTN; 605254) on chromosome 1q22-q23.
DESCRIPTION
Acne inversa is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses, predominantly in skin folds that carry terminal hairs and apocrine glands. Healing occurs with substantial scarring. The prevalence of acne inversa has been estimated at 1 in 100 to 1 in 600. The female-to-male ratio in most published series is between 2:1 and 5:1 (Jansen et al., 2001). Jansen et al. (2001) provided a detailed history and review of the disorder. - Genetic Heterogeneity of Familial Acne Inversa Familial acne inversa-2 (ACNINV2; 613736) is caused by haploinsufficiency for the PSENEN gene (607632) on chromosome 19q13.1. Familial acne inversa-3 (ACNINV3; 613737) is caused by haploinsufficiency for the PSEN1 gene (104311) on chromosome 14q24.3, making this disorder allelic to early-onset Alzheimer disease (607822).CLINICAL FEATURES
Fitzsimmons et al. (1984) observed chronic hidradenitis suppurativa in a total of 21 members (16 females, 5 males) from 3 English families. In 1 kindred, the condition was associated with acne conglobata (cystic acne) and vertical transmission through 3 generations was documented. In the other families, affected persons had a history of acne vulgaris with comedone formation and 2 generations were affected. No male-to-male transmission was documented; however, the authors stated that the grandfather in their family B was probably affected and, if true, this would mean one instance of father-to-son transmission. Several of the females were obese, but none had diabetes. Fitzsimmons et al. (1985) extended their studies to 23 families in which they found a total of 62 affected persons. Fitzsimmons and Guilbert (1985) reported a series based on 26 probands. 'Single gene transmission' was supported by the findings in 11 of these. In another 3 families, a history of other affected persons was obtained; in 9 families no history of other cases was found. Several of the families included persons with acne conglobata alone or with hidradenitis suppurativa.INHERITANCE
Knaysi et al. (1968) found a positive family history in 3 of 18 patients specifically questioned. In order to test the validity of dominant inheritance in hidradenitis suppurativa, Von der Werth et al. (2000) revisited 14 surviving probands and their families initially reported by Fitzsimmons and Guilbert (1985). Patients were evaluated by a newly devised, strict definition of the disorder. Von der Werth et al. (2000) directly evaluated 132 family members and detected 28 affected relatives, including 27 who were in the group previously labeled as family history-positive. Nine cases had not been detected previously, including 7 who developed symptoms after the previous study had been completed. Eighteen cases were classified as 'possibly affected,' including 2 that were classified as 'definitely affected' in the original study. All new cases in families with positive histories for hidradenitis suppurativa were descended from affected individuals, while none of the unaffected members of these families had affected children. In all, they found that 27% of surviving first-degree relatives were definitely affected, a figure lower than the 50% expected in an autosomal dominant disease. However, if they ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 142690 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed