Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Nicastrin

Gene

NCSTN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000162736-MONOMER.
ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-1980148. Signaling by NOTCH3.
R-HSA-1980150. Signaling by NOTCH4.
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.
SignaLinkiQ92542.
SIGNORiQ92542.

Names & Taxonomyi

Protein namesi
Recommended name:
Nicastrin
Gene namesi
Name:NCSTN
Synonyms:KIAA0253
ORF Names:UNQ1874/PRO4317
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:17091. NCSTN.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini34 – 669ExtracellularSequence analysisAdd BLAST636
Transmembranei670 – 690HelicalSequence analysisAdd BLAST21
Topological domaini691 – 709CytoplasmicSequence analysisAdd BLAST19

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

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.
See also OMIM:142690
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067756211P → R in ACNINV1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi336 – 337DY → AA: Increases production of amyloid beta (beta-APP40 and beta-APP42) in APP processing. 1 Publication2

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi23385.
MalaCardsiNCSTN.
MIMi142690. phenotype.
OpenTargetsiENSG00000162736.
Orphaneti387. Hidradenitis suppurativa.
PharmGKBiPA142671271.

Chemistry databases

ChEMBLiCHEMBL3418.

Polymorphism and mutation databases

BioMutaiNCSTN.
DMDMi12231037.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000001968134 – 709NicastrinAdd BLAST676

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi45N-linked (GlcNAc...)1 Publication1
Glycosylationi55N-linked (GlcNAc...)Sequence analysis1
Glycosylationi187N-linked (GlcNAc...)1 Publication1
Glycosylationi200N-linked (GlcNAc...)Sequence analysis1
Glycosylationi204N-linked (GlcNAc...)Sequence analysis1
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Glycosylationi387N-linked (GlcNAc...)2 Publications1
Glycosylationi417N-linked (GlcNAc...)Sequence analysis1
Glycosylationi435N-linked (GlcNAc...)Sequence analysis1
Glycosylationi464N-linked (GlcNAc...)Sequence analysis1
Glycosylationi506N-linked (GlcNAc...)Sequence analysis1
Glycosylationi530N-linked (GlcNAc...)Sequence analysis1
Glycosylationi562N-linked (GlcNAc...)Sequence analysis1
Glycosylationi573N-linked (GlcNAc...)Sequence analysis1
Glycosylationi580N-linked (GlcNAc...)Sequence analysis1
Glycosylationi612N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ92542.
MaxQBiQ92542.
PaxDbiQ92542.
PeptideAtlasiQ92542.
PRIDEiQ92542.
TopDownProteomicsiQ92542-2. [Q92542-2]

PTM databases

iPTMnetiQ92542.
PhosphoSitePlusiQ92542.
SwissPalmiQ92542.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

Constitutively expressed in neural cells.1 Publication

Gene expression databases

BgeeiENSG00000162736.
CleanExiHS_NCSTN.
ExpressionAtlasiQ92542. baseline and differential.
GenevisibleiQ92542. HS.

Organism-specific databases

HPAiCAB021982.
HPA054846.

Interactioni

Subunit structurei

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).

Binary interactionsi

WithEntry#Exp.IntActNotes
APH1AQ96BI33EBI-998440,EBI-2606935
PSEN1P497683EBI-998440,EBI-297277
PSENENQ9NZ423EBI-998440,EBI-998468
TMED10P497555EBI-998440,EBI-998422

Protein-protein interaction databases

BioGridi116961. 133 interactors.
DIPiDIP-36336N.
IntActiQ92542. 52 interactors.
MINTiMINT-3048708.
STRINGi9606.ENSP00000294785.

Chemistry databases

BindingDBiQ92542.

Structurei

Secondary structure

1709
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi665 – 697Combined sources33
Beta strandi698 – 700Combined sources3
Helixi704 – 706Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N7QNMR-A664-709[»]
2N7RNMR-A664-709[»]
4UISelectron microscopy4.40A42-665[»]
4UPCelectron microscopy5.40A1-709[»]
5A63electron microscopy3.40A1-709[»]
5FN2electron microscopy4.20A1-709[»]
5FN3electron microscopy4.10A1-709[»]
5FN4electron microscopy4.00A1-709[»]
5FN5electron microscopy4.30A1-709[»]
ProteinModelPortaliQ92542.
SMRiQ92542.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the nicastrin family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2657. Eukaryota.
ENOG410XT6X. LUCA.
GeneTreeiENSGT00390000014633.
HOGENOMiHOG000044212.
HOVERGENiHBG006497.
InParanoidiQ92542.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG091G03DV.
PhylomeDBiQ92542.
TreeFamiTF317086.

Family and domain databases

InterProiIPR008710. Nicastrin.
[Graphical view]
PANTHERiPTHR21092. PTHR21092. 1 hit.
PfamiPF05450. Nicastrin. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

This isoform has been chosen as the 'canonical' 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
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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti657R → H in AAH47621 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05027475V → I.Corresponds to variant rs12045198dbSNPEnsembl.1
Natural variantiVAR_05027577E → D.Corresponds to variant rs35603924dbSNPEnsembl.1
Natural variantiVAR_067756211P → R in ACNINV1. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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:
EMBLi
GenBanki
DDBJi
Links Updated
AF240468 mRNA. Translation: AAG11412.1.
AY359120 mRNA. Translation: AAQ89478.1.
AK314764 mRNA. Translation: BAG37302.1.
AL445230 Genomic DNA. Translation: CAI15009.1.
AL445230 Genomic DNA. Translation: CAI15010.1.
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]
CCDS76228.1. [Q92542-2]
RefSeqiNP_001277113.1. NM_001290184.1. [Q92542-2]
NP_001277115.1. NM_001290186.1.
NP_056146.1. NM_015331.2. [Q92542-1]
UniGeneiHs.517249.

Genome annotation databases

EnsembliENST00000294785; ENSP00000294785; ENSG00000162736. [Q92542-1]
ENST00000368063; ENSP00000357042; ENSG00000162736. [Q92542-2]
GeneIDi23385.
KEGGihsa:23385.
UCSCiuc001fvx.4. human. [Q92542-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Translation: CAI15009.1.
AL445230 Genomic DNA. Translation: CAI15010.1.
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]
CCDS76228.1. [Q92542-2]
RefSeqiNP_001277113.1. NM_001290184.1. [Q92542-2]
NP_001277115.1. NM_001290186.1.
NP_056146.1. NM_015331.2. [Q92542-1]
UniGeneiHs.517249.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N7QNMR-A664-709[»]
2N7RNMR-A664-709[»]
4UISelectron microscopy4.40A42-665[»]
4UPCelectron microscopy5.40A1-709[»]
5A63electron microscopy3.40A1-709[»]
5FN2electron microscopy4.20A1-709[»]
5FN3electron microscopy4.10A1-709[»]
5FN4electron microscopy4.00A1-709[»]
5FN5electron microscopy4.30A1-709[»]
ProteinModelPortaliQ92542.
SMRiQ92542.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116961. 133 interactors.
DIPiDIP-36336N.
IntActiQ92542. 52 interactors.
MINTiMINT-3048708.
STRINGi9606.ENSP00000294785.

Chemistry databases

BindingDBiQ92542.
ChEMBLiCHEMBL3418.

PTM databases

iPTMnetiQ92542.
PhosphoSitePlusiQ92542.
SwissPalmiQ92542.

Polymorphism and mutation databases

BioMutaiNCSTN.
DMDMi12231037.

Proteomic databases

EPDiQ92542.
MaxQBiQ92542.
PaxDbiQ92542.
PeptideAtlasiQ92542.
PRIDEiQ92542.
TopDownProteomicsiQ92542-2. [Q92542-2]

Protocols and materials databases

DNASUi23385.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000294785; ENSP00000294785; ENSG00000162736. [Q92542-1]
ENST00000368063; ENSP00000357042; ENSG00000162736. [Q92542-2]
GeneIDi23385.
KEGGihsa:23385.
UCSCiuc001fvx.4. human. [Q92542-1]

Organism-specific databases

CTDi23385.
DisGeNETi23385.
GeneCardsiNCSTN.
HGNCiHGNC:17091. NCSTN.
HPAiCAB021982.
HPA054846.
MalaCardsiNCSTN.
MIMi142690. phenotype.
605254. gene.
neXtProtiNX_Q92542.
OpenTargetsiENSG00000162736.
Orphaneti387. Hidradenitis suppurativa.
PharmGKBiPA142671271.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2657. Eukaryota.
ENOG410XT6X. LUCA.
GeneTreeiENSGT00390000014633.
HOGENOMiHOG000044212.
HOVERGENiHBG006497.
InParanoidiQ92542.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG091G03DV.
PhylomeDBiQ92542.
TreeFamiTF317086.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000162736-MONOMER.
ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-1980148. Signaling by NOTCH3.
R-HSA-1980150. Signaling by NOTCH4.
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.
SignaLinkiQ92542.
SIGNORiQ92542.

Miscellaneous databases

ChiTaRSiNCSTN. human.
GeneWikiiNicastrin.
GenomeRNAii23385.
PROiQ92542.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162736.
CleanExiHS_NCSTN.
ExpressionAtlasiQ92542. baseline and differential.
GenevisibleiQ92542. HS.

Family and domain databases

InterProiIPR008710. Nicastrin.
[Graphical view]
PANTHERiPTHR21092. PTHR21092. 1 hit.
PfamiPF05450. Nicastrin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNICA_HUMAN
AccessioniPrimary (citable) accession number: Q92542
Secondary accession number(s): Q5T207, Q5T208, Q86VV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 11, 2001
Last modified: November 30, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.