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]

PCSK1N
Identifiers
Aliases	PCSK1N, PROSAAS, SAAS, SCG8, SgVIII, BigLEN, PEN, proprotein convertase subtilisin/kexin type 1 inhibitor
External IDs	OMIM: 300399; MGI: 1353431; HomoloGene: 8315; GeneCards: PCSK1N; OMA:PCSK1N - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xp11.23 Start 48,831,096 bp[1] End 48,835,610 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X A1.1 Start 7,786,061 bp[2] End 7,790,649 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in anterior pituitary beta cell nucleus accumbens anterior cingulate cortex amygdala right frontal lobe caudate nucleus hypothalamus putamen dorsolateral prefrontal cortex Top expressed in entorhinal cortex perirhinal cortex median eminence central gray substance of midbrain arcuate nucleus ventromedial nucleus dorsomedial hypothalamic nucleus superior colliculus dorsal tegmental nucleus mammillary body More reference expression data BioGPS n/a
Gene ontology Molecular function endopeptidase inhibitor activity signaling receptor binding serine-type endopeptidase inhibitor activity Cellular component extracellular region trans-Golgi network Golgi apparatus secretory granule extracellular space Biological process response to dietary excess response to cold neuropeptide signaling pathway peptide hormone processing negative regulation of endopeptidase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 27344 30052 Ensembl ENSG00000102109 ENSMUSG00000039278 UniProt Q9UHG2 Q9QXV0 RefSeq (mRNA) NM_013271 NM_013892 RefSeq (protein) NP_037403 NP_038920 Location (UCSC) Chr X: 48.83 – 48.84 Mb Chr X: 7.79 – 7.79 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 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.