RRC ID 58260
Author Tsuji A, Kikuchi Y, Sato Y, Koide S, Yuasa K, Nagahama M, Matsuda Y.
Title A proteomic approach reveals transient association of reticulocalbin-3, a novel member of the CREC family, with the precursor of subtilisin-like proprotein convertase, PACE4.
Journal Biochem J
Abstract SPCs (subtilisin-like proprotein convertases) are a family of seven structurally related serine endoproteases that are involved in the proteolytic activation of proproteins. In an effort to examine the substrate protein for PACE4 (paired basic amino-acid-cleaving enzyme-4), an SPC, a potent protein inhibitor of PACE4, an alpha1-antitrypsin RVRR (Arg-Val-Arg-Arg) variant, was expressed in GH4C1 cells. Ectopic expression of the RVRR variant caused accumulation of the 48 kDa protein in cells. Sequence analysis indicates that the 48 kDa protein is a putative Ca2+-binding protein, RCN-3 (reticulocalbin-3), which had previously been predicted by bioinformatic analysis of cDNA from the human hypothalamus. RCN-3 is a member of the CREC (Cab45/reticulocalbin/ERC45/calumenin) family of multiple EF-hand Ca2+-binding proteins localized to the secretory pathway. The most interesting feature of the RCN-3 sequence is the presence of five Arg-Xaa-Xaa-Arg motifs, which represents the target sequence of SPCs. Biosynthetic studies showed that RCN-3 is transiently associated with proPACE4, but not with mature PACE4. Inhibition of PACE4 maturation by a Ca2+ ionophore resulted in accumulation of the proPACE4-RCN-3 complex in cells. Furthermore, autoactivation and secretion of PACE4 was increased upon co-expression with RCN-3. Our findings suggest that selective and transient association of RCN-3 with the precursor of PACE4 plays an important role in the biosynthesis of PACE4.
Volume 396(1)
Pages 51-9
Published 2006-5-15
DOI 10.1042/BJ20051524
PII BJ20051524
PMID 16433634
PMC PMC1449992
MeSH Adenoma / pathology Amino Acid Sequence Animals COS Cells Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism* Cell Line Cell Line, Tumor / metabolism Chlorocebus aethiops Enzyme Activation Furin / antagonists & inhibitors Humans Kidney / cytology Molecular Sequence Data Neoplasm Proteins / metabolism Pituitary Neoplasms / pathology Proprotein Convertase 5 / antagonists & inhibitors Proprotein Convertases Protein Binding Protein Precursors / genetics Protein Precursors / metabolism* Proteomics Rats Recombinant Fusion Proteins / metabolism Sequence Alignment Sequence Homology, Amino Acid Serine Endopeptidases / genetics Serine Endopeptidases / metabolism* Transfection alpha 1-Antitrypsin / chemistry alpha 1-Antitrypsin / genetics alpha 1-Antitrypsin / metabolism
IF 4.097
Times Cited 24
Altmetric score
オルトメトリクス指標項目
The most frequently cited source Patent(IFI CLAIMS)
Total number of mentions 16
Altmetric score changes over past 6months 0.0
Resource
DNA material Human Reticulocalbin 3 (RDB03412)