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Proprotein convertase subtilisin/kexin type 1 inhibitor

From Wikipedia, the free encyclopedia
(Redirected from ProSAAS)
PCSK1N
Identifiers
AliasesPCSK1N, PROSAAS, SAAS, SCG8, SgVIII, BigLEN, PEN, proprotein convertase subtilisin/kexin type 1 inhibitor
External IDsOMIM: 300399; MGI: 1353431; HomoloGene: 8315; GeneCards: PCSK1N; OMA:PCSK1N - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_013271

NM_013892

RefSeq (protein)

NP_037403

NP_038920

Location (UCSC)Chr X: 48.83 – 48.84 MbChr X: 7.79 – 7.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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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 accomplishes the initial proteolytic cleavage of peptide precursors. ProSAAS is further processed at the N- and C-termini into multiple short peptides, leaving the central segment intact. This 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] Recent data show that nigral proSAAS expression blocks the deterioration of the striatonigral pathway in a synuclein rat model of Parkinson's disease.[8] ProSAAS also oligomerizes and undergoes liquid-liquid phase separation.[9] Differential expression of this gene may be associated with obesity.

References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000102109 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039278 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: Proprotein convertase subtilisin/kexin type 1 inhibitor". Retrieved 2017-02-28.
  6. 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. Bibcode:2016PNAS..113E4708J. doi:10.1073/pnas.1601091113. PMC 4987805. PMID 27457957.
  7. 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.
  8. Lindberg I, Shu Z, Lam H, Helwig M, Yucer N, Laperle A, Svendsen CN, Di Monte DA, Maidment NT (2022). "The proSAAS Chaperone Provides Neuroprotection and Attenuates Transsynaptic α-Synuclein Spread in Rodent Models of Parkinson's Disease". J Parkinsons Dis. 12 (5): 1463–1478. doi:10.3233/JPD-213053. PMC 9731515. PMID 35527562.
  9. Peinado JR, Chaplot K, Jarvela TS, Barbieri EM, Shorter J, Lindberg I (2022). "Sequestration of TDP-43216-414 Aggregates by Cytoplasmic Expression of the proSAAS Chaperone". ACS Chem Neurosci. 13 (11): 1651–1665. doi:10.1021/acschemneuro.2c00156. PMC 9731516. PMID 35549000.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.