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0  structures 66  species 0  interactions 77  sequences 3  architectures

Family: GSAP-16 (PF14959)

Summary: gamma-Secretase-activating protein C-term

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gamma-Secretase-activating protein C-term Provide feedback

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) [1]. 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 [2].

Literature references

  1. 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

  2. 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


External database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(14)
Full
(77)
Representative proteomes NCBI
(85)
Meta
(0)
RP15
(17)
RP35
(22)
RP55
(37)
RP75
(53)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(14)
Full
(77)
Representative proteomes NCBI
(85)
Meta
(0)
RP15
(17)
RP35
(22)
RP55
(37)
RP75
(53)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(14)
Full
(77)
Representative proteomes NCBI
(85)
Meta
(0)
RP15
(17)
RP35
(22)
RP55
(37)
RP75
(53)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

This family is new in this Pfam release.

Seed source: Jackhmmer:A4D1B5
Previous IDs: none
Type: Family
Author: Coggill P
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 30.4 42.6
Noise cut-off 26.4 20.3
Model length: 115
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

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