PCSK9/NARC1  Protein, Antibody, ELISA Kit, cDNA Clone

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10594-H08H1-10
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11054-K08H-10
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PCSK9/NARC1 관련 경로

    PCSK9/NARC1 요약 및 단백질 정보

    PCSK9/NARC1 배경

    유전자 요약: This PCSK9 gene encodes a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family. PCSK9 is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the endoplasmic reticulum. PCSK9 may function as a proprotein convertase. PCSK9 plays a role in cholesterol homeostasis and may have a role in the differentiation of cortical neurons. Mutations in this gene have been associated with a third form of autosomal dominant familial hypercholesterolemia (HCHOLA3). [provided by RefSeq, Jul 2008]
    General information above from NCBI
    보조 인자: Calcium (Probable).
    효소 조절: Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA.
    하부단위 구조: Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers. Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR.
    도메인: The C-terminal domain (CRD) is essential for the LDLR- binding and degrading activities (PubMed:22027821).
    The catalytic domain is responsible for mediating its self-association.
    세포하 위치: Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus. Note=Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein. Localizes to the endoplasmic reticulum in the absence of LDLR and co-localizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR. The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation.
    조직 특이성: Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.
    번역 후: Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation.
    Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein.
    Phosphorylation protects the propeptide against proteolysis.
    질병과의 관련성: Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3) [MIM:603776]: A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins. Note=The disease is caused by mutations affecting the gene represented in this entry.
    염기서열 유사성: Belongs to the peptidase S8 family.
    Contains 1 peptidase S8 domain.
    General information above from UniProt

    Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as NARC1 (neural apoptosis regulated convertase), which is a newly identified human secretory subtilase belonging to the proteinase K subfamily of the secretory subtilase family. PCSK9 protein is an enzyme which in humans is encoded by the PCSK9 gene with orthologs found across many species. It is expressed in neuroepithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells. PCSK9 protein is highly expressed in the liver and regulates low density lipoprotein receptor (LDLR) protein levels. Inhibition of PCSK9 protein function is currently being explored as a means of lowering cholesterol levels. Thereby, PCSK9 protein is regarded as a new strategy to treat hypercholesterolemia. PCSK9 protein contributes to cholesterol homeostasis and may have a role in the differentiation of cortical neurons.

    References

    PCSK9/NARC1 대체 이름

    Macaca mulatta,PC9,Pcsk9, [canine]
    FH3,PC9,NARC1,LDLCQ1,NARC-1,HCHOLA3, [homo-sapiens]
    FH3,HCHOLA3,LDLCQ1,NARC1,NARC-1,PC9,PCSK9,PSEC0052, [human]
    AI415265,AI747682,FH3,HCHOLA3,MGC47409,Narc1,PC9,Pcsk9,RP23-159J7.1, [mouse]
    FH3,PC9,Narc1,HCHOLA3,AI415265,AI747682, [mus-musculus]
    Narc1,NARC-1,PC9,Pcsk9, [rat]

    PCSK9/NARC1 관련 연구

  • Sseidah, N.G. et al., 2003, Proc. Natl. Acad. Sci. USA. 100: 928-933.
  • Beyer, T.P. et al., 2007, J. Lipid. Res. 48: 1488-1498
  • Shan, L. et al., 2008, Biochem. Biophys. Res. Commun. 375: 69-73.
  • Benjannet, S. et al., 2005, J. Biol. Chem. 279: 48865-48875.
  • Abifadel, M. et al., 2003, Nat. Genet. 34: 154-156.
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