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)

Function: 1) control of neuroendocrine secretory pathway 2) specific endogenous inhibitor of PCSK1 3) 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 4) slows down convertase-mediated processing of proopiomelanocortin & proenkephalin 5) function of the processed secreted peptides is not known 6) proteolytically cleaved in the Golgi Compartment: - secreted, trans-Golgi network 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)

Properties

SIZE: MW = 27 kD entity length = 260 aa COMPARTMENT: cytoplasm golgi MOTIF: signal sequence {1-33} ProSAAS(1-180) {34-215} C-terminal inhibitory {221-260} MOTIF: L-L-R-V-K-R {239-244}

Database Correlations

OMIM 300399 UniProt Q9UHG2 Pfam PF07259

References

UniProt :accession Q9UHG2