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- Table of Contents
1 Citations 6 Q&As
Facts about NPC intracellular cholesterol transporter 2.
NPC2 binds unesterified cholesterol that has been released from LDLs from the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and can be exported from the limiting membrane of late endosomes/ lysosomes into the ER and plasma membrane by an unknown mechanism.
Human | |
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Gene Name: | NPC2 |
Uniprot: | P61916 |
Entrez: | 10577 |
Belongs to: |
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NPC2 family |
EDDM1; Epididymal Protein 1; epididymal secretory protein E1; HE1; HE1epididymal protein 1; Human epididymis-specific protein 1; MGC1333; Niemann-Pick disease type C2 protein; Niemann-Pick disease, type C2; NiemannPick Type C2; Niemann-Pick Type C2; NPC2; NP-C2; tissue-specific secretory protein
Mass (kDA):
16.57 kDA
Human | |
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Location: | 14q24.3 |
Sequence: | 14; NC_000014.9 (74479935..74493512, complement) |
Epididymis.
Secreted. Endoplasmic reticulum. Lysosome. Interaction with cell-surface M6PR mediates endocytosis and targeting to lysosomes.
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We have previously identified a new ligand, HarmNPC2-1 as potential ligands for the protein HarmNPC1. Its high affinity for 1-NPN, a probe that is fluorescent that allows us to investigate its interactions with proteins. We performed affinity titrations with 1-NPN and methanol to determine the dissociation coefficients for each ligand.
In comparison to the native protein it was more hydrophobic than the human counterpart. It had a glycan region connected to its polypeptide chain and thus was easily soluble. Its aggregation characteristics were also improved. This resulted in a higher capability to detect ligands. HarmNPC2-1 was also compatible with the new ligand.
The gene is expressed in different regions of the H. armigera, including the antennae. It is most abundant at sensilla Chaetica, which is an organ of sensory function that is dedicated to contact Chemoreception. We also observed the presence of heavy staining in hemolymph vessels as predicted by the Western Blot experiment. These results suggest that HarmNPC2-1 is involved in chemodeception within these insects.
The docking of HarmNPC2-1 to querecetin may enhance the antiviral activity of tumor necrosis factor (TNF) by targeting key amino acid residues in the active site. It also inhibits the activity of the cyclooxygenase enzyme responsible for the synthesizing and release of prostanoids. Additionally, quercetin blocks the activity of 15-lipoxygenase, which is responsible for oxidation of low-density lipoprotein.
To study the docking of Quercetin with the TMPRSS-2 receptor, a molecular dynamics simulation of the ligand and its binding pocket was performed. The complex reached convergence at 30 ns. The RMSD of Quercetin and Genistein increased by 0.61 A and LEU419 respectively, and was stable for 50 ns. A conformational cluster analysis revealed that the complexes were composed of two major conformation groups.
Quercetin has the ability to prevent the common cold and the flu by blocking the translation of capsid proteins. It also blocks expression genes and proteins that are responsible for sexual reproduction in male rats of adult age. Quercetin is a final word that reduces the risk of infection by human rhinoviruses. It regulates the expression of HSV genome genes and sperm quality.
Another important finding of this study was that HarmNPC2-1 may be tuned to bind non-volatile Ligands. In insects the protein is abundant in the sensilla chaetica, which are specialized for contact Chemoreception. In arthropods, it is likely that the NPC2 family proteins are the sole soluble proteins, whereas OBPs and CSPs are a scarce or not present outside of Hexapoda and Crustacea. CSPs however, on the other being, aren't found in the Hexapoda or Crustacea and play a minor role in the process of chemodetection.
The docking of HarmNPC2-1 with querecetin showed that the natural compound was extremely compatible with the viral spike glycoprotein (SPG). The protein also demonstrated good binding affinity with ASP88. However, more research is required to determine if quercetin is a feasible candidate for therapeutic use. The drug has been subjected to an FDA review in the US which is a positive sign for future drug development.
We'll have to find the mechanism(s) by which these miRNAs may interact with SARS-CoV-2 later on. Our initial results indicate that Quercetin is a key molecule. Its docking with the SARS-2 proteins could form the basis of a novel drug to combat corona virus infections. So, the next step is to examine the role of quercetin in the regulation of the expression of the SARS-CoV-2 gene.
Recent studies have also demonstrated quercetin is a good drug candidate for treating COVID-19. The substance blocks several genes that are involved in the immune system and has excellent safety profile. Quercetin is stable within the body and is a powerful anti-inflammatory and antioxidant properties. The docking of HarmNPC2-1 with quercetin can boost antiviral activity by inhibiting key enzymes in the respiratory system.
An important goal of environmental-friendly pest management is to eliminate or reduce the risk of insecticide residues from crops and landscapes. Pests can be controlled or prevented despite their numerous negative impacts. These include changing crop rotations and using less sensitive crops and employing biological control agents in addition to using less risky pesticides. Potential targets for environmentally-friendly pest control with the NPC2 marker will help in the selection of pesticides.
It is vital to develop tools that are sustainable, cost-effective and safeguard human health when using ecologically sound pest-management strategies. Conventional pest-control methods rely on chemical substances and encourage short-term solutions, which can be harmful to the environment or to the health of humans. Broad-spectrum chemical solutions often fail to tackle the cause of some pests. Future pest-management systems will have broader knowledge of the agroecosystem and will seek to control pests.
PMID: 8418812 by Krull N., et al. Region-specific variation of gene expression in the human epididymis as revealed by in situ hybridization with tissue-specific cDNAs.
PMID: 17018531 by Liou H.L., et al. NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols.
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