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  4. Recombinant Human Gamma-secretase subunit APH-1A (APH1a)

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

  • 中文名稱：
    Recombinant Human Gamma-secretase subunit APH-1A(APH1a)
  • 品名簡稱：
    Recombinant Human APH1a protein
  • 貨號：
    CSB-CF853390HU
  • 說明書：
  • 規格：
    ￥9720
  • 圖片：
    • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • 其他：

產品詳情

  • 純度：
    Greater than 90% as determined by SDS-PAGE.
  • 基因名：
  • Uniprot No.：
  • 別名：
    APH1A; PSF; CGI-78; UNQ579/PRO1141; Gamma-secretase subunit APH-1A; APH-1a; Aph-1alpha; Presenilin-stabilization factor
  • 種屬：
    Homo sapiens(Human)
  • 蛋白長度：
    Full?Length?of Isoform 2
  • 來源：
    in vitro E.coli expression system
  • 分子量：
    42.9kDa
  • 表達區域：
    1-247aa
  • 氨基酸序列
    MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQRSLLCKD
    Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
    If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.
  • 蛋白標簽：
    N-terminal 6xHis-SUMO-tagged
  • 產品提供形式：
    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.
  • 緩沖液：
    Lyophilized from Tris/PBS-based buffer, 6% Trehalose
  • 儲存條件：
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保質期：
    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.
  • 貨期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
    Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
  • 注意事項：
    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.

產品評價

靶點詳情

  • 功能：
    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). Required for normal gamma-secretase assembly. The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.
  • 基因功能參考文獻：
    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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  • 亞細胞定位：
    Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus, Golgi stack membrane; Multi-pass membrane protein.
  • 蛋白家族：
    APH-1 family
  • 組織特異性：
    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.
  • 數據庫鏈接：

    HGNC: 29509

    OMIM: 607629

    KEGG: hsa:51107

    STRING: 9606.ENSP00000358105

    UniGene: Hs.108408



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