APH1A Antibody

1. Using purified PSEN1/Aph1A gamma-secretase and the APPC99-3XFLAG substrate, authors show that substrate shortening progressively destabilizes the consecutive enzyme-substrate complexes that characterize the sequential gamma-secretase processing of APP; present a unifying model for how PSEN or APP mutations enhance amyloidogenic Abeta production, suggests that environmental factors may increase Alzheimer's Disease risk. PMID: 28753424
2. Data show that presenilin 1 (PS1)/anterior-pharynx-defective protein 1 (Aph1b), presenilin 2 (PS2)/Aph1aL, PS2/Aph1aS and PS2/anterior pharynx defective 1 homolog B (Aph1b) gamma-secretase produced amyloid beta peptide (Abeta) with a higher Abeta42+Abeta43-to-Abeta40 (Abeta42(43)/Abeta40) ratio than the other gamma-secretases. PMID: 27608597
3. Data show that presenilin 1 (PS1)-containing gamma-secretase complexes were targeted to the plasma membrane, whereas presenilin 2 (PS2)-containing ones were addressed to the trans-Golgi network, to recycling endosomes. PMID: 27059953
4. No statistically significant difference was detected either in APOE or APH-1a polymorphisms, not suggesting a strong susceptibility to the development of Alzheimer disease. PMID: 26738354
5. A loss of PS/gamma-secretase function to cleave Abeta42(43) may initiate Alzheimer's disease. PMID: 23291095
6. We demonstrate that extending the transmembrane domain of the amyloid precursor protein-derived C99 substrate in proximity to the cytosolic face strongly influences gamma-secretase cleavage specificity. PMID: 23253155
7. The -980C/G polymorphism in APH-1A promoter confers risk of Alzheimer's disease PMID: 21443683
8. Coexpression of wild-type or S-palmitoylation-deficient APH1aL and nicastrin leads to marked stabilization of transgenic presenilin 1 in the brains of double-transgenic mice. PMID: 21123562
9. Endogenous Aph-1a and its proteolytic fragment have unique properties for cleavage control that may have implications for gamma-secretase regulation and intracellular distribution. PMID: 20674680
10. Co-overexpression of presenilin-1 or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 into the gamma-secretase complex PMID: 20299451
11. Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates PMID: 20145246
12. APH-1 binds to presenilins and nicastrin and may play a role in maturation of presenilin-nicastrin complexes PMID: 12471034
13. Expression of APH-1A increases amyloid beta peptide levels and gamma-secretase activity. PMID: 12763021
14. APH-1 and the gamma-secretase complex bind to the transmembrane domain region of nicastrin PMID: 12917438
15. Six different polymorphisms have been determined but the polymorphisms in APH-1a/b coding regions are not linked to higher risk for Alzheimer disease in an Italian population. PMID: 12972157
16. APH-1 can be processed by several endoproteolytic events and generates a stable C-terminal fragment that associates with nicastrin PMID: 14593096
17. conserved transmembrane Gly122, Gly126, and Gly130 in the fourth transmembrane region of APH-1a are part of the membrane helix-helix interaction GXXXG motif and are essential for the stable association of APH-1aL with presenilin, nicastrin, and PEN-2 PMID: 14627705
18. Only the combined overexpression of presenilin 1 and nicastrin together with APH-1a G122D facilitated the formation of a fully active gamma-secretase complex PMID: 15210705
19. both APH-1a splice forms and APH-1b are expressed in peripheral and neuronal cells. APH-1aS, APH-1aL, and APH-1b form separate, proteolytically active gamma-secretase complexes containing either one of the two presenilins. PMID: 15286082
20. knock down of APH-1a, but not APH-1b, resulted in impaired maturation of nicastrin and reduced expression of presenilin 1, presenilin 2, and PEN-2 proteins PMID: 15629423
21. These results collectively indicate that the three forms of APH-1 can replace each other in presenilin (PS) complexes and that the transmembrane GxxxG region is essential for the stability of the APH-1 protein as well as the assembly of PS complexes. PMID: 16757808
22. Over-expression of APH-1 and inhibition of proteasomal APH-1 degradation facilitated gamma-secretase cleavage of APP to generate Abeta. Thus,degradation of APH-1 protein is mediated by the ubiquitin-proteasome pathway. PMID: 17059559
23. analysis of model of the gamma-secretase complex subunit architecture and demonstration of the close proximity of the C-terminal fragment of presenilin with APH-1 PMID: 18801744
24. that there is an association between the -980C/G polymorphism in the APH-1a promoter region and the development of sporadic Alzheimer's disease PMID: 19368855
25. the conserved transmembrane histidine residues contribute to APH1 function and can affect presenilin catalytic activity PMID: 19369254

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HGNC: 29509

OMIM: 607629

KEGG: hsa:51107

STRING: 9606.ENSP00000358105

UniGene: Hs.108408