Summary: gamma-Secretase-activating protein C-term
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GSAP, or gamma-secretase-activating protein, also known as PION, regulates gamma-secretase activity. The holo-protein is a large, approx 850 residue protein that is rapidly cleaved to an active 16 kDa C-terminal fragment that is the stable, predominant form. GSAP is expressed in inclusion bodies and is important in brain function. It dramatically and selectively increases neurotoxic beta-Amyloid production in the brain through a mechanism involving its interactions with both gamma-secretase and its substrate, the amyloid precursor protein C-terminal fragment (APP-CTF). Accumulation of neurotoxic beta-Amyloid is a major hallmark of Alzheimer's disease. Formation of beta-Amyloid is catalysed by gamma-secretase, a protease with numerous substrates that catalyses the intra-membrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein) . The secondary structure of GSAP is largely alpha-helical, lacking well-defined tertiary structure. GSAP represents a type of gamma-secretase regulator that directs enzyme specificity by interacting with a specific substrate .
He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Wennogle LP, Greengard P;, Nature. 2010;467:95-98.: Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. PUBMED:20811458 EPMC:20811458
Deatherage CL, Hadziselimovic A, Sanders CR;, Biochemistry. 2012; [Epub ahead of print]: Purification and Characterization of the Human gamma-Secretase Activating Protein. PUBMED:22681044 EPMC:22681044
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This family is new in this Pfam release.
|Number in seed:||14|
|Number in full:||77|
|Average length of the domain:||111.40 aa|
|Average identity of full alignment:||39 %|
|Average coverage of the sequence by the domain:||13.83 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||1|
|Download:||download the raw HMM for this family|
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