Proprotein convertase subtilisin/kexin type 1 inhibitor
Proprotein convertase subtilisin/kexin type 1 inhibitor is a protein by the name of proSAAS that in humans is encoded by the PCSK1N gene. [5]
Function
This protein is expressed largely in cells possessing a regulated secretory pathway, such as endocrine/neuroendocrine cells and neurons. The intact proSAAS protein, as well as the carboxyy-terminal peptide containing the inhibitory hexapeptide LLRVKR, functions as an inhibitor of prohormone convertase 1/3, which regulates the proteolytic cleavage of peptide precursors. ProSAAS is further processed into multiple short peptides. Differential expression of this gene may be associated with obesity. The central, unprocessed portion of the protein may function as a neural- and endocrine-specific chaperone due to its potent ability to block the aggregation of beta amyloid and alpha synuclein in vitro, and to block oligomer cytotoxicity in cells.[6][7][8]
References
- GRCh38: Ensembl release 89: ENSG00000102109 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000039278 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: Proprotein convertase subtilisin/kexin type 1 inhibitor". Retrieved 2017-02-28.
- Jarvela TS, Lam HA, Helwig M, Lorenzen N, Otzen DE, McLean PJ, Maidment NT, Lindberg I (2016). "The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity". Proc Natl Acad Sci U S A. 113 (32): E4708-15. doi:10.1073/pnas.1601091113. PMC 4987805. PMID 27457957.
- Hoshino A, Helwig M, Rezaei S, Berridge C, Eriksen JL, Lindberg I (2014). "A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease". J Neurochem. 128 (3): 419–30. doi:10.1111/jnc.12454. PMC 3946950. PMID 24102330.
- Jarvela TS, Lam HA, Helwig M, Lorenzen N, Otzen DE, McLean PJ, Maidment NT, Lindberg I (2016). "The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity". Proc Natl Acad Sci U S A. 113 (32): E4708-15. doi:10.1073/pnas.1601091113. PMC 4987805. PMID 27457957.
Further reading
- Fortenberry Y, Hwang JR, Apletalina EV, Lindberg I (2002). "Functional characterization of ProSAAS: similarities and differences with 7B2". J. Biol. Chem. 277 (7): 5175–86. doi:10.1074/jbc.M104531200. PMID 11719503.
- Wada M, Ren CH, Koyama S, Arawaka S, Kawakatsu S, Kimura H, Nagasawa H, Kawanami T, Kurita K, Daimon M, Hirano A, Kato T (2004). "A human granin-like neuroendocrine peptide precursor (proSAAS) immunoreactivity in tau inclusions of Alzheimer's disease and parkinsonism-dementia complex on Guam". Neurosci. Lett. 356 (1): 49–52. doi:10.1016/j.neulet.2003.11.028. PMID 14746899.
- Kudo H, Liu J, Jansen EJ, Ozawa A, Panula P, Martens GJ, Lindberg I (2009). "Identification of proSAAS homologs in lower vertebrates: conservation of hydrophobic helices and convertase-inhibiting sequences". Endocrinology. 150 (3): 1393–9. doi:10.1210/en.2008-1301. PMC 2654743. PMID 18948394.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.