Recombinant Human Gamma-secretase subunit PEN-2 (PSENEN)

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Code CSB-CF878932HU
Size $1620
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 85% as determined by SDS-PAGE.
Target Names
PSENEN
Uniprot No.
Research Area
Neuroscience
Alternative Names
PSENEN; PEN2; MDS033; Gamma-secretase subunit PEN-2; Presenilin enhancer protein 2
Species
Homo sapiens (Human)
Source
in vitro E.coli expression system
Expression Region
1-101aa
Target Protein Sequence
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
14.8 kDa
Protein Length
Full Length
Tag Info
N-terminal 10xHis-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
Lyophilized from Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°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
3-7 business days
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.

Customer Reviews and Q&A

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Target Background

Function
Essential 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). 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 (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity.
Gene References into Functions
  1. High gamma-secretase expression is associated with head and neck squamous cell carcinoma. PMID: 29047105
  2. APP substrate occupancy of these three pockets of gamma-secretase occurs after initial substrate binding but precedes catalysis, suggesting a conformational change in substrate may be required for cleavage. PMID: 27580372
  3. PSENEN mutations can indeed cause a comanifestation of Dowling-Degos disease and acne inversa (AI) that is likely triggered by predisposing factors for AI. PMID: 28287404
  4. zinc, copper inhibited Abeta production by directly targeting the subunits presenilin and nicastrin in the gamma-secretase complex PMID: 28096459
  5. PSENEN may play a crucial role in the progression of atopic dermatitis by participating in the Notch signaling pathway. PMID: 26967585
  6. Remarkably, PEN-2 was identified besides nicastrin as additional substrate-binding subunit. PMID: 27220847
  7. Results suggest deltaOR-Phe27Cys variation modulates beta- and gamma-secretase activity in late-stage Alzheimer's disease likely via post-translational mechanisms PMID: 26402014
  8. TRPC6 specifically interacts with APP leading to inhibition of its cleavage by gamma-secretase and reduction in Abeta production. PMID: 26581893
  9. secondary mutations in presenilin 1 alone activated the gamma-secretase activity. PMID: 26559975
  10. Both human PS2V and zebrafish PS1IV can stimulate gamma-secretase activity despite extreme structural divergence PMID: 25814654
  11. Data indicate that familial Alzheimer's disease (FAD) and control brain samples had similar overall gamma-secretase activity levels, and therefore, loss of overall (endopeptidase) gamma-secretase function cannot be an essential part of the pathogenic mechanism. PMID: 26481686
  12. We for the first time identify PEN-2 as the causative gene of familial comedones. PMID: 26044244
  13. The first hydrophobic domain of Pen-2 forms a structure similar to a reentrant loop while the second hydrophobic domain spans the lipid bilayer. PMID: 26296997
  14. shedding of BCMA by gamma-secretase controls plasma cells in the bone marrow and yields a potential biomarker for B-cell involvement in human autoimmune diseases PMID: 26065893
  15. Tumor necrosis factor-alpha and interleukin-10 levels were elevated in acne inversa patients with nicastrin or presenilin enhancer mutation. PMID: 26067312
  16. SLC2A13 is a novel gamma-secretase associated protein that regulates amyloid beta production without affecting Notch cleavage. PMID: 26094765
  17. Brain proteins showing neuron-specific interactions with gamma-secretase PMID: 25893612
  18. A complete inhibition of PS1-induced apoptosis was achieved by knockdown of PS1-associated protein (PSAP), a mitochondrial proapoptotic protein that forms a complex with Bax upon induction of apoptosis, in the presence of gamma-secretase inhibitor. PMID: 26025363
  19. analysis of how the conformation of presenilin, Pen-2, Aph-1, and nicastrin affect the function and mechanism of gamma-secretase PMID: 25918421
  20. Mutation of on PS1 and PS2 AXXXAXXXG motifs strongly impacts gamma-secretase activity. PMID: 25614624
  21. The catalytic subunit of gamma-secretase is presenilin 1 (PS1), which contains an initial substrate-binding site that is distinct from the catalytic site PMID: 25673856
  22. Recombinant human Pen-2 fusion protein was purified from bacteria to >95% purity. PMID: 24865334
  23. Together, our results suggest that iron can increase gamma-secretase activity through promoting the level of FTL that interacts with and stabilizes PEN-2/ PMID: 23685131
  24. A review of mutations in the gamma-secretase genes NCSTN, PSENEN, and PSEN1 and the role of gamma-secretase in cutaneous biology and, more specifically in hidradenitis suppurativa. PMID: 23096707
  25. Allele A of Pen 2 gene may increase the risk of late onset Alzheimer's disease. PMID: 23134962
  26. a 269 bp region located between the PSENEN and U2AF1L4 human genes is a genuine bidirectional promoter regulating a concerted divergent transcription of these genes. PMID: 23246698
  27. Mutations in the gamma-secretase genes NCSTN, PSENEN, and PSEN1 underlie rare forms of hidradenitis suppurativa (acne inversa). PMID: 22622421
  28. The molecular state of gamma-secretase and its enzymological characteristics are described. PMID: 22787762
  29. secretase subunits restrict the arrangement of the transmembrane domains of presenilin during the formation of the functional structure of the catalytic pore. PMID: 22689582
  30. Studies indicate that gradual saturation of gamma-secretase with its substrate can be the pathogenic process in different alleged causes of Alzheimer's disease (AD). PMID: 22479317
  31. expression of calsenilin leads to a disruption of presenilin 1/gamma-secretase-mediated epsilon-cleavage of N-cadherin, which results in the significant accumulation of N-cadherin C-terminal fragment 1 PMID: 21852538
  32. NCSTN and PSENEN, are involved in the pathogenesis of some familial hidradenitis suppurativa (Acne Inversa). PMID: 21412258
  33. structural analysis of PEN-2 conformation by single-particle electron microscopy PMID: 21454611
  34. This study support a gamma-secretase-independent role of presenilin-1 in modulation of filamin-mediated actin cytoskeleton. PMID: 20847418
  35. study found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN in 6 Chinese acne inversa (AI) families; results identify the gamma-secretase component genes as culprits for a subset of familial AI PMID: 20929727
  36. Data show that intramembranous cleavage by gamma-secretase and related intramembrane-cleaving proteases may generally occur via stepwise endoproteolysis. PMID: 20534834
  37. Hematopoietic gamma-secretase has reduced activity for APP and Notch1 processing compared to epithelial gamma-secretase. PMID: 20178366
  38. Transactivation of the Pen2 promoter by presenilin 1/2 is p53-dependent. PMID: 19889971
  39. a component of the gamma-secretase complex PMID: 12198112
  40. role in regulating proteolytic processing of presenilin 1 in conjunction with APH-1 PMID: 12522139
  41. examination of membrane topology PMID: 12639958
  42. APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex. PMID: 12660785
  43. Expression of PEN2 increases amyloid beta peptide levels and gamma-secretase activity. PMID: 12763021
  44. presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, associate with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons PMID: 15322084
  45. the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes PMID: 15322109
  46. The presenilin-subunit stabilizing function of PEN-2 depends on length and overall sequence of its carboxyl-terminal domain. PMID: 15953349
  47. knockdown of ubiquilin-1 and -2 protein expression by RNAi (RNA interference) increased Pen-2 and nicastrin levels PMID: 15975090
  48. mutational analyses revealed that the "NF" sequence within the TMD4 of PS1 is the minimal motif that is required for binding with PEN-2, promoting PS1 endoproteolysis and gamma-secretase activity PMID: 16234243
  49. Pen-2 may contribute to the activation of the gamma-secretase complex by directly binding to the TMD4 of PS1 PMID: 16234244
  50. COX-2 may be a downstream effector of mutant N141I PS2-mediated apoptotic cell death and that inhibition of COX-2 may neuroprotect in AD through modulation of a GSK-3beta-beta-catenin-mediated response. PMID: 16331303

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Involvement in disease
Acne inversa, familial, 2 (ACNINV2)
Subcellular Location
Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus, Golgi stack membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein.
Protein Families
PEN-2 family
Tissue Specificity
Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain.
Database Links

HGNC: 30100

OMIM: 607632

KEGG: hsa:55851

STRING: 9606.ENSP00000222266

UniGene: Hs.534465

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