proSAAS (pro-SAAS, roprotein convertase subtilisin/kexin type 1 inhibitor, proprotein convertase 1 inhibitor, [Contains: KEP; Big SAAS (b-SAAS); Little SAAS (l-SAAS) (N-proSAAS); Big PEN-LEN (b-PEN-LEN) (SAAS CT(1-49)); PEN; Little LEN (l-LEN); Big LEN (b-LEN) (SAAS CT(25-40))], PCSK1N)
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Function
- control of neuroendocrine secretory pathway
- specific endogenous inhibitor of PCSK1
- ProSAAS & Big PEN-LEN
- both contain the C-terminal inhibitory domai
- diminish PCSK1 activity in endoplasmic reticulum & Golgi
- diminish activity of 84 kD form but not autocatalytically derived 66 kD form of PCSK1
- processing of proSAAS may eliminate the inhibition
- may regulate intracellular timing of PCSK1 rather than its total level of activity
- ProSAAS(1-180) increases secretion of enzymatically inactive PCSK1
- Big PEN-LEN contains the hexapeptide 'L-L-R-V-K-R' sufficient for PCSK1 inhibition
- slows down convertase-mediated processing of proopiomelanocortin & proenkephalin
- function of the processed secreted peptides is not known
- proteolytically cleaved in the Golgi
Compartment
Expression
expressed in brain & pancreas
Pathology
- N-terminal processed peptide, probably Big SAAS or Little SAAS, is accumulated in cytoplasmic protein tau deposits in: frontotemporal dementia parkinsonism linked to chromosome 17 (Pick disease) Alzheimer disease amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 (Guam disease)