APH-1 (anterior pharynx-defective 1) is a
proteingene product originally identified in the
Notch signaling pathway in Caenorhabditis elegans as a regulator of the cell-surface localization of
nicastrin.[1] APH-1 homologs in other organisms, including humans, have since been identified as components of the
gamma secretase complex along with the catalytic subunit
presenilin and the regulatory subunits
nicastrin and
PEN-2. The gamma-secretase complex is a multimeric
protease responsible for the intramembrane
proteolysis of
transmembrane proteins such as the Notch protein and
amyloid precursor protein (APP). Gamma-secretase cleavage of APP is one of two proteolytic steps required to generate the
peptide known as
amyloid beta, whose
misfolded form is implicated in the causation of
Alzheimer's disease.[2] All of the components of the gamma-secretase complex undergo extensive
post-translational modification, especially proteolytic activation; APH-1 and PEN-2 are regarded as regulators of the maturation process of the catalytic component presenilin.[3] APH-1 contains a conserved
alpha helix interaction
motifglycine-X-X-X-
glycine (
GXXXG) that is essential to both assembly of the gamma secretase complex and to the maturation of the components.[4]
APH-1 (anterior pharynx-defective 1) is a
proteingene product originally identified in the
Notch signaling pathway in Caenorhabditis elegans as a regulator of the cell-surface localization of
nicastrin.[1] APH-1 homologs in other organisms, including humans, have since been identified as components of the
gamma secretase complex along with the catalytic subunit
presenilin and the regulatory subunits
nicastrin and
PEN-2. The gamma-secretase complex is a multimeric
protease responsible for the intramembrane
proteolysis of
transmembrane proteins such as the Notch protein and
amyloid precursor protein (APP). Gamma-secretase cleavage of APP is one of two proteolytic steps required to generate the
peptide known as
amyloid beta, whose
misfolded form is implicated in the causation of
Alzheimer's disease.[2] All of the components of the gamma-secretase complex undergo extensive
post-translational modification, especially proteolytic activation; APH-1 and PEN-2 are regarded as regulators of the maturation process of the catalytic component presenilin.[3] APH-1 contains a conserved
alpha helix interaction
motifglycine-X-X-X-
glycine (
GXXXG) that is essential to both assembly of the gamma secretase complex and to the maturation of the components.[4]