Inter-α-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily

Salier, Jean‐Philippe

doi:10.1016/0968-0004(90)90282-g

Cited by 129 publications

(104 citation statements)

References 25 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…The archetypal Kunitz-type inhibitory domain [21,46,47] and cystatin domain [2] are shown as a box with critical disulphide bonds (of type A or B in the cystatin domain) symbolized by dotted lines outside. The residues that are critical for the inhibitory activity are written in upper (Kunitz motif, n l 4-6) or lower (cystatin motif) positions inside the box.…”

Section: Figure 4 Proven or Potential Protease Inhibitory Sites In Fementioning

confidence: 99%

Fetuin-B, a second member of the fetuin family in mammals

Olivier

Soury

Ruminy

et al. 2000

Biochemical Journal

Self Cite

111

View full text Add to dashboard Cite

A set of orthologous plasma proteins found in human, sheep, pig, cow and rodents, now collectively designated fetuin-A, constitutes the fetuin family. Fetuin-A has been identified as a major protein during fetal life and is also involved in important functions such as inhibition of the insulin receptor tyrosine kinase activity, protease inhibitory activities and development-associated regulation of calcium metabolism and osteogenesis. Furthermore, fetuin-A is a key partner in the recovery phase of an acute inflammatory response. We now describe a second protein of the fetuin family, called fetuin-B, which is found at least in human and rodents. On grounds of domain homology, overall conservation of cysteine residues and chromosomal assignments of the corresponding genes in these species, fetuin-B is unambiguously a paralogue of fetuin-A. Yet, fetuin-A and fetuin-B exhibit significant differences at the amino acid sequence level, notably including variations with respect to the archetypal fetuin-specific signature. Differences and similarities in terms of gene regulation were also observed. Indeed, studies performed during development in rat and mouse showed for the first time high expression of a member of the fetuin family in adulthood, as shown with the fetuin-B mRNA in rat. However, like its fetuin-A counterpart, the fetuin-B mRNA level is down-regulated during the acute phase of experimentally induced inflammation in rat.

show abstract

Section: Figure 4 Proven or Potential Protease Inhibitory Sites In Fementioning

confidence: 99%

Fetuin-B, a second member of the fetuin family in mammals

Olivier

Soury

Ruminy

et al. 2000

Biochemical Journal

Self Cite

111

View full text Add to dashboard Cite

show abstract

“…It is synthesized in hepatocytes from an mRNA encoding a precursor protein, ~-mbikunin [2]. Bikunin is a Kunitz type proteinase inhibitor [3] which has stimulatory effects on some cells [4,5] and is essential for the building of extracellular matrix [6]. The ~]-m-bikunin precursor is cleaved intracellularly, and free c~-m secreted from the hepatocytes [7].…”

Section: Hepg2 Cell Culture In Serum-l?ee Mediummentioning

confidence: 99%

Formation of the α₁‐microglobulin chromophore in mammalian and insect cells: a novel post‐translational mechanism?

1995

View full text Add to dashboard Cite

a~-Microglobulin is an immunosuppressive plasma protein synthesized by the liver. The isolated protein is yellowbrown, but the hypothetical chromophore has not yet been identified. In this work, it is shown that a human liver cell line, HepG2, grown in a completely synthetic and serum-free medium, secretes ~cmicroglobulin which is also yellow-brown, suggesting a de novo synthesis of the chromophore by the cells, at-Microglobulin isolated from the culture medium of insect cells transfected with the gene for rat a~-microglobulin is also yellow-brown, suggesting that the gene carries information about the chromophore. Reduction and alkylation or removal of N-or O-linked carbohydrates by glycosidase treatment did not reduce the colour intensity of the protein. An internal dodecapeptide (amino acid positions 70-81 in human aj-microglobulin) was also yellow-brown. The latter results indicate that the chromophore is linked to the polypeptide. in conclusion, the results suggest that the a~-microglobulin gene carries information activating a post-translational protein modification mechanism which is present in mammalian and insect cells.

show abstract

“…The ITI family molecules are synthesized by hepatocytes and secreted into blood at high concentrations (0.15-0.5 mg/ml plasma) (12). The heavy chains (HC1, HC2, and HC3) of these molecules are derived from three different genes, and either one or two of them are covalently bound to the light chain, bikunin, to form the ITI family members such as ITI, pre-␣-trypsin inhibitor (P␣I), and inter-␣-trypsin-like inhibitor (13). Bikunin carries at the serine residue at position 10 an O-glycosidically linked chondroitin sulfate chain, to which the heavy chains are linked via ester bonds of exactly the same type as that in a SHAP-HA complex (10,14).…”

mentioning

confidence: 99%

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Yingsung

Zhuo

Mörgelin

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

We previously found that a covalent complex of SHAPs (serum-derived hyaluronan-associated proteins), the heavy chains of inter-␣-trypsin inhibitor family molecules, with hyaluronan (HA) is accumulated in synovial fluid of patients with rheumatoid arthritis, and the complex is circulated in patient plasma at high concentrations. How the SHAP-HA complex participates in this disease is unknown. To address this question, it is essential to clarify the structural features of this macromolecule. The SHAP-HA complex purified from synovial fluid of the patients by three sequential CsCl isopycnic centrifugations was heterogeneous in density, and the fractions with different densities had distinct SHAPto-HA ratios. Agarose gel electrophoresis and column chromatography revealed that there was no apparent difference in the size distribution of HA to which SHAPs were bound between the fractions with different densities. The SHAP-HA complex in the higher density fraction had fewer SHAP molecules per HA chain. Therefore, the difference between the fractions with different densities was due to a heterogeneous population of the SHAP-HA complex, namely the different number of SHAP molecules bound to an HA chain. Based on the SHAP and HA contents of the purified preparations, we estimated that an HA chain with a molecular weight of 2 ؋ 10 6 has as many as five covalently bound SHAPs, which could give a proteinaceous multivalency to HA. Furthermore, we also found that the SHAP-HA complex tends to form aggregates, judging from the migration and elution profiles in agarose gel electrophoresis and gel filtration, respectively. The multivalent feature of the SHAP-HA complex was also confirmed by the negative staining electron micrographic images of the purified fractions. Taken together, those structural characteristics may underlie the aggregate-forming and extracellular matrix-stabilizing ability of the SHAP-HA complex.

show abstract

Inter-α-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily

Cited by 129 publications

References 25 publications

Fetuin-B, a second member of the fetuin family in mammals

Fetuin-B, a second member of the fetuin family in mammals

Formation of the α₁‐microglobulin chromophore in mammalian and insect cells: a novel post‐translational mechanism?

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Contact Info

Product

Resources

About

Inter-α-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily

Cited by 129 publications

References 25 publications

Fetuin-B, a second member of the fetuin family in mammals

Fetuin-B, a second member of the fetuin family in mammals

Formation of the α1‐microglobulin chromophore in mammalian and insect cells: a novel post‐translational mechanism?

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Contact Info

Product

Resources

About

Formation of the α₁‐microglobulin chromophore in mammalian and insect cells: a novel post‐translational mechanism?