LEKTI, a novel 15-domain type of human serine proteinase inhibitor.
Proteinase inhibitors are important negative regulators of proteinase action in vivo. We have succeeded in isolating two previously unknown polypeptides (HF6478 and HF7665) from human blood filtrate that are parts of a larger precursor protein containing two typical Kazal-type serine proteinase inhibitor motifs. The entire precursor protein, as deduced from the nucleotide sequence of the cloned cDNA, exhibits 15 potential inhibitory domains, including the Kazal-type domains, HF6478, HF7665, and 11 additional similar domains. An inhibitory effect of HF7665 on trypsin activity is demonstrated. Because all of the 13 HF6478- and HF7665-related domains share partial homology to the typical Kazal-type domain but lack one of the three conserved disulfide bonds, they may represent a novel type of serine proteinase inhibitor. The gene encoding the multidomain proteinase inhibitor, which we have termed LEKTI, was localized on human chromosome 5q31-32. As shown by reverse transcriptase-polymerase chain reaction and Northern blot analysis, it is expressed in the thymus, vaginal epithelium, Bartholin's glands, oral mucosa, tonsils, and the parathyroid glands. From these results, we assume that LEKTI may play a role in anti-inflammatory and/or antimicrobial protection of mucous epithelia.
Lower Saxony Institute for Peptide Research, Feodor-Lynen-Strasse 31, D-30 625 Hannover, Germany. HJ-Maegert@gmx.de
H J
HJ
Mägert
L
L
Ständker
P
P
Kreutzmann
H D
HD
Zucht
M
M
Reinecke
C P
CP
Sommerhoff
H
H
Fritz
W G
WG
Forssmann
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D014357:Trypsin / Q000378:metabolism*; D014462:Ultrafiltration
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors; D014357:Trypsin