The acid‐stable proteinase inhibitor of human mucous secretions (HUSI‐I, antileukoprotease)

Seemüller, Ursula; Arnhold, Marianne; Fritz, Hans; Wiedenmann, Karin; Machleidt, Werner; Heinzel, Regina; Appelhans, Heribert; Gassen, Hans Günter; Lottspeich, Friedrich

doi:10.1016/0014-5793(86)81220-0

Cited by 175 publications

(67 citation statements)

References 14 publications

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“…The prepeptide cleavage site is presumed to be between the amino acids glycine and serine at positions -1 and + 1. This presumption is supported by protein sequence data [9], which report the sequence Ser-Gly-Lys-Ser as the first NH2-terminal amino acids of ALP (Fig. 3).…”

Section: Isolation Of Mrnamentioning

confidence: 68%

“…An open reading frame of 273 bp encodes 90 amino acids of the COOH-terminus followed by the stop codon TGA. The DNA-derived amino acid sequence is supported by the known protein sequence data of antileukoprotease of seminal plasma [9]. To obtain a cDNA clone with the nucleotide sequence encoding the NH2-terminal part of the protein a thud oligonucleotide (RH5, 2Omer) was synthesized which is complementary to a coding sequence in plasmid pRH31 from positions 151 to 170 (Figs 1 and 3).…”

Section: Isolation Of Mrnamentioning

confidence: 99%

“…In consequence it has been impossible to determine the complete amino acid sequence of the native inhibitor until very recently [9]. In fact, inhibitory characteristics determined so far have been obtained only with mixtures of multiple inhibitor forms.…”

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confidence: 99%

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Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus

Heinzel

Appelhans

Gassen

et al. 1986

European Journal of Biochemistry

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We have isolated cDNA clones for the human antileukoprotease HUSI-I, an elastase inhibitor, from a library, containing cDNA inserts made from human cervix uterus. A library of 10000 recombinants was screened using a mixture of 16 different oligodeoxyribonucleotides which correspond to amino acids 79 -84 and one 20mer oligodeoxyribonucleotide corresponding to amino acids 19 -26. Two overlapping cDNA clones, containing the entire coding sequence and part of the 5'-and 3'-untranslated region, were isolated. DNA sequence data showed that our clone corresponds with the available protein sequence data. For expression, the cDNA fragment was inserted in a derivative of plasmid pPLc236 and expressed under the control of APL promoter. Expression of antileukoprotease was proven by Western blot analysis and inhibition of chymotrypsin.Neutral granulocytic proteinases as well as kallikreins are known to be potent mediators of the inflammatory response following polytraumatic injuries [I, 21. In vivo inhibition of these proteinases by low-molecular-mass inhibitors could serve as a valuable tool to decrease the inflammatory reaction [l, 3,4]. Human mucous fluids such as seminal plasma, cervical mucus, tears, bronchial and nasal secretions contain acidstable proteinase inhibitors with strong affinity for trypsin and chymotrypsin as well as for neutrophil lysosomal elastase and cathepsin G [5, 61. These inhibitors are characterized by their acid stability and low molecular mass. The antileukoprotease from human seminal plasma HUSI-I (human seminal plasma inhibitor I) and the inhibitor found in mucous secretions, from the cervix uteri, although isolated from different tissues seem to be identical proteins based on shared characteristics of acid stability and low molecular mass [I], partial amino acid sequence homology [7], inhibition spectrum and immuno-cross-reactivity [S]. We shall therefore refer to them jointly as ALP (antileukoprotease). The isolation of the inhibitor from human seminal plasma is complicated

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Section: Isolation Of Mrnamentioning

confidence: 68%

Section: Isolation Of Mrnamentioning

confidence: 99%

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Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus

Heinzel

Appelhans

Gassen

et al. 1986

European Journal of Biochemistry

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“…The italicized amino acid residues (from position 176 to 182) correspond to the known active site region of SLPI which is a protein that consists of two WAP motifs (18,57). The binding site of SKALP/elafin with elastase is found at the amino acid sequence Leu 176 (P5)-Leu 182 (P2Ј), which contains the scissile peptide bond Ala 180 -Met 181 (35), which is marked by a vertical arrow (2).…”

Section: Cross-linking Of the Biotinylated Peptides To Purified Protementioning

confidence: 99%

Identification and Sequence Analysis of Two New Members of the SKALP/elafin and SPAI-2 Gene Family

Zeeuwen¹,

Hendriks²,

Jong³

et al. 1997

Journal of Biological Chemistry

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The human epithelial proteinase inhibitor SKALP/elafin and the porcine sodium-potassium ATPase inhibitor SPAI-2 are two highly homologous proteins that share an NH 2 -terminal transglutaminase substrate domain and a COOH-terminal whey acidic protein (WAP) domain. Here we describe the bovine and simian orthologs of SKALP/elafin as well as two new bovine family members that are designated Trappin-4 and Trappin-5 on the basis of a new nomenclature that we propose (Trappin ‫؍‬ TRansglutaminase substrate and WAP motif-containing ProteIN). Sequence analysis of Trappin-4 and Trappin-5 revealed a domain structure that is very similar to SPAI-2 (Trappin-1) and SKALP/elafin (Trappin-2). The transglutaminase substrate motifs are conserved although the number of repeats varies among species and among family members. The sequence of Trappin-4 and Trappin-5 diverges from Trappin-1 and Trappin-2 at the putative reactive site in the WAP domain. The bovine ortholog of Trappin-2 is expressed in tongue and snout epidermis; Trappin-4 is expressed in trachea, ileum, and tongue; and Trappin-5 is expressed at low levels in trachea, as determined by RNase protection and Northern blot analysis. Based on the analysis of 67 transglutaminase substrate repeats as present in all known Trappin gene family members from four different mammalian species a consensus sequence could be established: GlyGln-Asp-Pro-Val-Lys (GQDPVK). Using biotinylated hexapeptide probes we found that the GQDPVK sequence is a very efficient transglutaminase substrate both for guinea pig liver transglutaminase and for epidermal transglutaminase, and it acts as acyl donor as well as acceptor. We propose that the Trappin protein family forms a new group of enzyme inhibitors with various specificities of the WAP domain, which share transglutaminase substrate motifs that can act as an anchoring sequence. Skin-derived antileukoproteinase (SKALP)1 (1) and sodiumpotassium ATPase inhibitor-2 (SPAI-2) (2) are two molecules that share an NH 2 -terminal domain that functions as a transglutaminase (TGase) substrate, and a COOH-terminal whey acidic protein (WAP) domain that harbors an inhibitory activity toward at least two distinct enzymes. Porcine SPAI-2 was the first of these molecules to be described and is expressed mainly in the intestine (3). Human SKALP, otherwise known as elafin (4), or elastase-specific inhibitor (5), is a potent inhibitor of the leukocytic proteinases elastase and proteinase-3 (6, 7). We found that SKALP/elafin is expressed in several human stratifying squamous epithelia, except for epidermis where it is only expressed in the context of inflammation, such as psoriasis or wound healing (8 -10). We mapped the genomic localization of human SKALP/elafin to chromosome 20q12-13 (11). Interestingly, this region contains various other genes involved in TGase-mediated cross-linking processes such as the tissue TGase gene (12), epidermal TGase (13, 14), and the genes coding for semenogelin I and semenogelin II (15), which are also epithelial TGase substrates. SKAL...

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“…The activity, and probably the function, of proteases in semen may be influenced by seminal protease inhibitors. Several low molecular weight, acid stable peptide protease inhibitors, detected because of their activity against trypsin, chymotrypsin, acrosin, neutrophil elastase, and/or kallikrein, have been isolated from seminal plasma of a number of species, including mouse [16], boar [26], bull [11], horse [27], and human [19,21]. These inhibitors, like those against cysteine proteases [3,12], are secreted mainly from the seminal vesicles.…”

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confidence: 99%

Reverse Zymography Studies of Protease Inhibitors in the Secretions of Different Lobes of Rat Prostate

Wilson

Casey

Woodson

et al. 1999

Archives of Andrology

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The acid‐stable proteinase inhibitor of human mucous secretions (HUSI‐I, antileukoprotease)

Cited by 175 publications

References 14 publications

Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus

Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus

Identification and Sequence Analysis of Two New Members of the SKALP/elafin and SPAI-2 Gene Family

Reverse Zymography Studies of Protease Inhibitors in the Secretions of Different Lobes of Rat Prostate

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