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UniProtKB - Q92542 (NICA_HUMAN)

Entry version 186 (16 Oct 2019)
Sequence version 2 (11 Jan 2001)
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Protein

Nicastrin

Gene

NCSTN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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.6 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processNotch signaling pathway

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-193692 Regulated proteolysis of p75NTR
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-6798695 Neutrophil degranulation
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus
R-HSA-9017802 Noncanonical activation of NOTCH3
R-HSA-977225 Amyloid fiber formation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q92542

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q92542

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Nicastrin
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:NCSTN
Synonyms:KIAA0253
ORF Names:UNQ1874/PRO4317
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:17091 NCSTN

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		605254 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q92542

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini34 – 669Extracellular2 PublicationsAdd BLAST636
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei670 – 690Helical2 PublicationsAdd BLAST21
Topological domaini691 – 709Cytoplasmic2 PublicationsAdd BLAST19

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Acne inversa, familial, 1 (ACNINV1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_067756211P → R in ACNINV1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi336 – 337DY → AA: Increases production of amyloid-beta (beta-APP40 and beta-APP42) in APP processing. 1 Publication2
Mutagenesisi653W → A or F: No effect on gamma-secretase activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		23385

MalaCards human disease database

More...MalaCardsi		NCSTN
MIMi142690 phenotype

Open Targets

More...OpenTargetsi		ENSG00000162736

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		387 NON RARE IN EUROPE: Hidradenitis suppurativa

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA142671271

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q92542

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3418

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		NCSTN

Domain mapping of disease mutations (DMDM)

More...DMDMi		12231037

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 33Sequence analysisAdd BLAST33
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001968134 – 709NicastrinAdd BLAST676

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi45N-linked (GlcNAc...) asparagineCombined sources4 Publications1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi50 ↔ 62Combined sources2 Publications4 Publications
Glycosylationi55N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Disulfide bondi140 ↔ 159Combined sources4 Publications
Glycosylationi187N-linked (GlcNAc...) asparagineCombined sources4 Publications1
Disulfide bondi195 ↔ 213Combined sources1 Publication2 Publications
Glycosylationi200N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi204N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi230 ↔ 248Combined sources1 Publication4 Publications
Glycosylationi264N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi387N-linked (GlcNAc...) asparagineCombined sources5 Publications1
Glycosylationi417N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi435N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi464N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi506N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi530N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi562N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi573N-linked (GlcNAc...) asparagineSequence analysisCombined sources3 Publications1
Glycosylationi580N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi586 ↔ 620Combined sources4 Publications
Glycosylationi612N-linked (GlcNAc...) asparagine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N-glycosylated.5 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q92542

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q92542

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q92542

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q92542

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q92542

PeptideAtlas

More...PeptideAtlasi		Q92542

PRoteomics IDEntifications database

More...PRIDEi		Q92542

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		75302 [Q92542-1]
75303 [Q92542-2]

Consortium for Top Down Proteomics

More...TopDownProteomicsi		Q92542-2 [Q92542-2]

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		1567

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q92542

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q92542

SwissPalm database of S-palmitoylation events

More...SwissPalmi		Q92542

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Detected in brain (at protein level) (PubMed:10993067). Widely expressed (PubMed:11396676).2 Publications

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Constitutively expressed in neural cells.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000162736 Expressed in 224 organ(s), highest expression level in placenta

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q92542 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q92542 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB021982
HPA054846
HPA070642

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Component of the gamma-secretase complex (PubMed:10993067, PubMed:30598546, PubMed:30630874). 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 PSENEN/PEN2 (PubMed:12740439, PubMed:25043039, PubMed:26623517, PubMed:26280335, PubMed:25918421, PubMed:30598546, PubMed:30630874). Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP) (PubMed:10993067, PubMed:30630874).

Interacts with PSEN1 and PSEN2 (PubMed:10993067).

8 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		116961, 140 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-2176 Gamma-secretase complex, APH1A-PSEN1 variant
CPX-4231 Gamma-secretase complex, APH1A-PSEN2 variant
CPX-4232 Gamma-secretase complex, APH1B-PSEN2 variant
CPX-4233 Gamma-secretase complex, APH1B-PSEN1 variant

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q92542

Database of interacting proteins

More...DIPi		DIP-36336N

Protein interaction database and analysis system

More...IntActi		Q92542, 86 interactors

Molecular INTeraction database

More...MINTi		Q92542

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000294785

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q92542

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1709
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q92542

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the nicastrin family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2657 Eukaryota
ENOG410XT6X LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00390000014633

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000044212

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q92542

KEGG Orthology (KO)

More...KOi		K06171

Identification of Orthologs from Complete Genome Data

More...OMAi		SYGSEFA

Database of Orthologous Groups

More...OrthoDBi		1166960at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q92542

TreeFam database of animal gene trees

More...TreeFami		TF317086

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR041084 Ncstrn_small
IPR008710 Nicastrin

The PANTHER Classification System

More...PANTHERi		PTHR21092 PTHR21092, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF18266 Ncstrn_small, 1 hit
PF05450 Nicastrin, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q92542-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MATAGGGSGA DPGSRGLLRL LSFCVLLAGL CRGNSVERKI YIPLNKTAPC 
        60         70         80         90        100
VRLLNATHQI GCQSSISGDT GVIHVVEKEE DLQWVLTDGP NPPYMVLLES 
       110        120        130        140        150
KHFTRDLMEK LKGRTSRIAG LAVSLTKPSP ASGFSPSVQC PNDGFGVYSN 
       160        170        180        190        200
SYGPEFAHCR EIQWNSLGNG LAYEDFSFPI FLLEDENETK VIKQCYQDHN 
       210        220        230        240        250
LSQNGSAPTF PLCAMQLFSH MHAVISTATC MRRSSIQSTF SINPEIVCDP 
       260        270        280        290        300
LSDYNVWSML KPINTTGTLK PDDRVVVAAT RLDSRSFFWN VAPGAESAVA 
       310        320        330        340        350
SFVTQLAAAE ALQKAPDVTT LPRNVMFVFF QGETFDYIGS SRMVYDMEKG 
       360        370        380        390        400
KFPVQLENVD SFVELGQVAL RTSLELWMHT DPVSQKNESV RNQVEDLLAT 
       410        420        430        440        450
LEKSGAGVPA VILRRPNQSQ PLPPSSLQRF LRARNISGVV LADHSGAFHN 
       460        470        480        490        500
KYYQSIYDTA ENINVSYPEW LSPEEDLNFV TDTAKALADV ATVLGRALYE 
       510        520        530        540        550
LAGGTNFSDT VQADPQTVTR LLYGFLIKAN NSWFQSILRQ DLRSYLGDGP 
       560        570        580        590        600
LQHYIAVSSP TNTTYVVQYA LANLTGTVVN LTREQCQDPS KVPSENKDLY 
       610        620        630        640        650
EYSWVQGPLH SNETDRLPRC VRSTARLARA LSPAFELSQW SSTEYSTWTE 
       660        670        680        690        700
SRWKDIRARI FLIASKELEL ITLTVGFGIL IFSLIVTYCI NAKADVLFIA 

PREPGAVSY
Length:709
Mass (Da):78,411
Last modified:January 11, 2001 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iC8C0EAEAD89E976A
GO
Isoform 2 (identifier: Q92542-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-29: LSFCVLLAG → MDFNLILES

Note: No experimental confirmation available.
Show »
Length:689
Mass (Da):76,744
Checksum:i58A8EE3F50F93459
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T209Q5T209_HUMAN
Nicastrin
NCSTN
255Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q5T210Q5T210_HUMAN
Nicastrin
NCSTN
232Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q5T211Q5T211_HUMAN
Nicastrin
NCSTN
134Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8YE20A0A2R8YE20_HUMAN
Nicastrin
NCSTN
71Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y6T7H0Y6T7_HUMAN
Nicastrin
NCSTN
275Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q5T205Q5T205_HUMAN
Nicastrin
NCSTN
219Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2U3TZL9A0A2U3TZL9_HUMAN
Nicastrin
NCSTN
69Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y3Z4H0Y3Z4_HUMAN
Nicastrin
NCSTN
316Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8YCK1A0A2R8YCK1_HUMAN
Nicastrin
NCSTN
69Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti657R → H in AAH47621 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05027475V → I. Corresponds to variant dbSNP:rs12045198Ensembl.1
Natural variantiVAR_05027577E → D. Corresponds to variant dbSNP:rs35603924Ensembl.1
Natural variantiVAR_067756211P → R in ACNINV1. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0083851 – 20Missing in isoform 2. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_00838621 – 29LSFCVLLAG → MDFNLILES in isoform 2. 1 Publication9

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF240468 mRNA Translation: AAG11412.1
AY359120 mRNA Translation: AAQ89478.1
AK314764 mRNA Translation: BAG37302.1
AL445230 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52720.1
CH471121 Genomic DNA Translation: EAW52721.1
CH471121 Genomic DNA Translation: EAW52722.1
BC047621 mRNA Translation: AAH47621.1
D87442 mRNA Translation: BAA13383.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS1203.1 [Q92542-1]

NCBI Reference Sequences

More...RefSeqi		NP_001277113.1, NM_001290184.1 [Q92542-2]
NP_001277115.1, NM_001290186.1
NP_056146.1, NM_015331.2 [Q92542-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000294785; ENSP00000294785; ENSG00000162736 [Q92542-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		23385

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:23385

UCSC genome browser

More...UCSCi		uc001fvx.4 human [Q92542-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240468 mRNA Translation: AAG11412.1
AY359120 mRNA Translation: AAQ89478.1
AK314764 mRNA Translation: BAG37302.1
AL445230 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52720.1
CH471121 Genomic DNA Translation: EAW52721.1
CH471121 Genomic DNA Translation: EAW52722.1
BC047621 mRNA Translation: AAH47621.1
D87442 mRNA Translation: BAA13383.1
CCDSiCCDS1203.1 [Q92542-1]
RefSeqiNP_001277113.1, NM_001290184.1 [Q92542-2]
NP_001277115.1, NM_001290186.1
NP_056146.1, NM_015331.2 [Q92542-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N7QNMR-A664-709[»]
2N7RNMR-A664-709[»]
4UISelectron microscopy4.40A42-665[»]
5A63electron microscopy3.40A1-709[»]
5FN2electron microscopy4.20A1-709[»]
5FN3electron microscopy4.10A1-709[»]
5FN4electron microscopy4.00A1-709[»]
5FN5electron microscopy4.30A1-709[»]
6IDFelectron microscopy2.70A1-709[»]
6IYCelectron microscopy2.60A1-709[»]
SMRiQ92542
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi116961, 140 interactors
ComplexPortaliCPX-2176 Gamma-secretase complex, APH1A-PSEN1 variant
CPX-4231 Gamma-secretase complex, APH1A-PSEN2 variant
CPX-4232 Gamma-secretase complex, APH1B-PSEN2 variant
CPX-4233 Gamma-secretase complex, APH1B-PSEN1 variant
CORUMiQ92542
DIPiDIP-36336N
IntActiQ92542, 86 interactors
MINTiQ92542
STRINGi9606.ENSP00000294785

Chemistry databases

BindingDBiQ92542
ChEMBLiCHEMBL3418

PTM databases

GlyConnecti1567
iPTMnetiQ92542
PhosphoSitePlusiQ92542
SwissPalmiQ92542

Polymorphism and mutation databases

BioMutaiNCSTN
DMDMi12231037

Proteomic databases

EPDiQ92542
jPOSTiQ92542
MassIVEiQ92542
MaxQBiQ92542
PaxDbiQ92542
PeptideAtlasiQ92542
PRIDEiQ92542
ProteomicsDBi75302 [Q92542-1]
75303 [Q92542-2]
TopDownProteomicsiQ92542-2 [Q92542-2]

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		23385

Genome annotation databases

EnsembliENST00000294785; ENSP00000294785; ENSG00000162736 [Q92542-1]
GeneIDi23385
KEGGihsa:23385
UCSCiuc001fvx.4 human [Q92542-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		23385
DisGeNETi23385

GeneCards: human genes, protein and diseases

More...GeneCardsi		NCSTN
HGNCiHGNC:17091 NCSTN
HPAiCAB021982
HPA054846
HPA070642
MalaCardsiNCSTN
MIMi142690 phenotype
605254 gene
neXtProtiNX_Q92542
OpenTargetsiENSG00000162736
Orphaneti387 NON RARE IN EUROPE: Hidradenitis suppurativa
PharmGKBiPA142671271

Human Unidentified Gene-Encoded large proteins database

More...HUGEi		Search...

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2657 Eukaryota
ENOG410XT6X LUCA
GeneTreeiENSGT00390000014633
HOGENOMiHOG000044212
InParanoidiQ92542
KOiK06171
OMAiSYGSEFA
OrthoDBi1166960at2759
PhylomeDBiQ92542
TreeFamiTF317086

Enzyme and pathway databases

ReactomeiR-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-193692 Regulated proteolysis of p75NTR
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-6798695 Neutrophil degranulation
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus
R-HSA-9017802 Noncanonical activation of NOTCH3
R-HSA-977225 Amyloid fiber formation
SignaLinkiQ92542
SIGNORiQ92542

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		NCSTN human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Nicastrin

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		23385
PharosiQ92542

Protein Ontology

More...PROi		PR:Q92542

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000162736 Expressed in 224 organ(s), highest expression level in placenta
ExpressionAtlasiQ92542 baseline and differential
GenevisibleiQ92542 HS

Family and domain databases

InterProiView protein in InterPro
IPR041084 Ncstrn_small
IPR008710 Nicastrin
PANTHERiPTHR21092 PTHR21092, 1 hit
PfamiView protein in Pfam
PF18266 Ncstrn_small, 1 hit
PF05450 Nicastrin, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiNICA_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q92542
Secondary accession number(s): Q5T207, Q5T208, Q86VV5
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 11, 2001
Last modified: October 16, 2019
This is version 186 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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