PMID- 10542292
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - Molecular identification and characterization of novel membrane-bound
      metalloprotease, the soluble secreted form of which hydrolyzes a variety of
      vasoactive peptides.
PG  - 32469-77
AB  - One class of zinc metalloproteases, represented by neutral endopeptidase 24.11
      and endothelin-converting enzyme, has been shown to be involved in proteolytic
      activation or inactivation of many regulatory peptides. Here, we report molecular
      cloning and characterization of a novel member of this type II membrane-bound
      metalloprotease family, termed soluble secreted endopeptidase (SEP). Alternative 
      splicing results in the generation of another transcript, SEP(Delta), which lacks
      a 69-base pair nucleotide segment following the transmembrane helix. Both SEP and
      SEP(Delta) mRNA are detected in all mouse tissues examined. Transfection of an
      SEP cDNA expression construct resulted in the expression of the membrane-bound
      form of SEP in the early secretory pathway as well as the soluble secreted form
      of the enzyme in the culture medium. In contrast, transfection of the SEP(Delta) 
      cDNA only results in the expression of the membrane-bound form. In vitro
      enzymological analysis of the recombinant soluble form of SEP demonstrated that
      it hydrolyzes a variety of vasoactive peptides, including endothelin-1, atrial
      natriuretic peptide, and angiotensin I. This activity of SEP was inhibited by
      phosphoramidon and the neutral endopeptidase 24.11 specific inhibitor thiorphan, 
      but it was only partially inhibited by the endothelin-converting enzyme specific 
      inhibitor FR901533. These findings suggest that SEP is a novel metalloprotease
      that possesses a broad substrate specificity and that it may be involved in the
      metabolism of biologically active peptides intracellulary as well as
      extracellularly.
FAU - Ikeda, K
AU  - Ikeda K
AD  - Division of Genetics, International Center for Medical Research, Kobe University 
      School of Medicine, 7-5-1 Kusunoki, Chuo, Kobe 6500017, Japan.
FAU - Emoto, N
AU  - Emoto N
FAU - Raharjo, S B
AU  - Raharjo SB
FAU - Nurhantari, Y
AU  - Nurhantari Y
FAU - Saiki, K
AU  - Saiki K
FAU - Yokoyama, M
AU  - Yokoyama M
FAU - Matsuo, M
AU  - Matsuo M
LA  - eng
SI  - GENBANK/AF157105
SI  - GENBANK/AF157106
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (Endothelin-1)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Tetracyclines)
RN  - 157110-24-2 (WS 79089B)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.- (soluble secreted endopeptidase)
RN  - EC 3.4.24.71 (Endothelin-Converting Enzymes)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Angiotensin I/*metabolism
MH  - Animals
MH  - Aspartic Acid Endopeptidases/genetics/physiology
MH  - Atrial Natriuretic Factor/*metabolism
MH  - Base Sequence
MH  - CHO Cells
MH  - Cricetinae
MH  - DNA, Complementary/chemistry
MH  - Endothelin-1/*metabolism
MH  - Endothelin-Converting Enzymes
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Hydrolysis
MH  - Metalloendopeptidases/genetics/*isolation & purification/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Solubility
MH  - Tetracyclines/pharmacology
MH  - Transfection
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32469 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32469-77. doi: 10.1074/jbc.274.45.32469.