Recombinant Human Gamma-secretase subunit APH-1A(APH1a),partial

Code CSB-CF853390HU
Size US$1235
Image
  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

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Product Details

Purity Greater than 90% as determined by SDS-PAGE.
Target Names APH1A
Uniprot No. Q96BI3
Research Area Others
Alternative Names 6530402N02Rik; AL138795.3; Anterior Pharynx Defective 1; Anterior pharynx defective 1 homolog A; APH 1A; Aph 1alpha; APH-1a; Aph-1alpha; Aph1a; APH1A gamma secretase subunit; APH1A_HUMAN; CGI 78; CGI78; Gamma secretase subunit APH 1A; Gamma Secretase Subunit APH1a; Gamma-secretase subunit APH-1A; Likely ortholog of C. elegans anterior pharynx defective 1A; Presenilin Stabilization Factor; Presenilin-stabilization factor; PSF; UNQ579/PRO1141
Species Homo sapiens (Human)
Source in vitro E.coli expression system
Expression Region 1-247aa
Target Protein Sequence MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQRSLLCRR
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 42.9kDa
Protein Length Partial
Tag Info N-terminal 6xHis-SUMO-tagged
Form Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

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Target Data

Function Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein)
Gene References into Functions
  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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Subcellular Location Endoplasmic reticulum membrane, Multi-pass membrane protein, Golgi apparatus, Golgi stack membrane, Multi-pass membrane protein
Protein Families APH-1 family
Tissue Specificity Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain. Isoform 1 and isoform 2 are nearly expressed at the same level.
Database Links

HGNC: 29509

OMIM: 607629

KEGG: hsa:51107

STRING: 9606.ENSP00000358105

UniGene: Hs.108408

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