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nicastrin (NCSTN, KIAA0253, UNQ1874/PRO4317)

Function: - subunit of the APP gamma-secretase - probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex - interacts with presenilins 1 & 2 - role in presenilin mediated processing of APP gamma-secretase & notch signalling - binds to proteolytic processed C-terminal fragments C83 & C99 of the amyloid precursor protein (APP) Structure: - type 1 transmembrane glycoprotein - belongs to the nicastrin family Compartment: - membrane; type 1 membrane protein Alternative splicing: named isoforms=2 Expression: - widely expressed - constitutively expressed in neural cells Pathology: - one of 3 components of APP gamma-secretase complex in which haploinsufficiency is associated with hidradenitis suppurativa

General

glycoprotein membrane protein

Properties

SIZE: entity length = 709 aa MW = 78 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-33} N-glycosylation site {N45} N-glycosylation site {N55} N-glycosylation site {N187} N-glycosylation site {N200} N-glycosylation site {N204} N-glycosylation site {N264} N-glycosylation site {N387} N-glycosylation site {N417} N-glycosylation site {N435} N-glycosylation site {N464} N-glycosylation site {N506} N-glycosylation site {N530} N-glycosylation site {N562} N-glycosylation site {N573} N-glycosylation site {N580} N-glycosylation site {N612} transmembrane domain {670-690}

Database Correlations

OMIM 605254 UniProt Q92542 Pfam PF05450 Entrez Gene 23385 Kegg hsa:23385

References

  1. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature. 2000 Sep 7;407(6800):48-54. PMID: 10993067
  2. Entrez Gene :accession 23385
  3. UniProt :accession Q92542

Component-of

APP gamma-secretase