Complete amino acid sequence of human hemopexin, the heme-binding protein of serum.

Takahashi, Nobuhiro; Takahashi, Yōko; Putnam, Frank W.

doi:10.1073/pnas.82.1.73

Cited by 99 publications

(56 citation statements)

References 16 publications

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“…The glycoprotein is mainly produced by the hepatocyte, cleared by the hepatocyte-specific membrane receptor, and recycled (13 ). It carries 5 N-glycans on its N-terminus and is a type II acute phase protein (13,14 ). Finally, Hpx has no polymorphisms and does not bind any other plasma protein (13 ).…”

Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

Diagnostic Value of the Hemopexin N-Glycan Profile in Hepatocellular Carcinoma Patients

et al. 2010

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BACKGROUND: Hepatocellular carcinoma (HCC) is a common and rapidly fatal cancer. Current diagnostic methods for HCC have poor sensitivity and specificity, are invasive, and carry risk for complications. Newer markers are needed to overcome these problems and allow diagnosis of HCC at an earlier stage. In view of known associations between glycosylation changes and liver disease, we focused on the serum glycoprotein hemopexin and the specific characteristics of this liversynthesized glycoprotein.

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Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

Diagnostic Value of the Hemopexin N-Glycan Profile in Hepatocellular Carcinoma Patients

et al. 2010

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“…10 Human hemopexin has a molecular weight of $59 kDa, of which 80% (49,292 Da) is attributable to its 439 amino acid residues and the remaining 20% is attributable to glycosylation in the form of bi-or triantennary carbohydrate structures including a currently unique N-terminal glycan. 49,50,53,54 Human hemopexin is nearly monomorphic insofar as it exhibits polymorphisms only among black populations where very low levels of two other alleles have been reported. 5,55,56 Confusion over the molecular weight of native human hemopexin may arise from apparent molecular weights reported on the basis of SDS-PAGE analyses because hemopexin exhibits an apparent molecular weight that is $25% greater under reducing conditions than that observed under nonreducing conditions.…”

Section: Potential Chemical and Structural Modification Of Hemopexinmentioning

confidence: 99%

“…21,49 The corresponding heme-free proteins are also relatively resistant to proteolysis except for the linker region that connects the N-and Cdomains, which is susceptible to cleavage upon limited hydrolysis with trypsin or plasmin. 1,35,50 However, human hemopexin that is prepared by the acidified acetone procedure 51 is rapidly cleaved into many fragments by trypsin. 49 Use of correctly folded hemopexin is as important to the assessment of its interaction(s) with cells and other biological activities as it is in all other functional studies of hemopexin.…”

Section: Modification Of Hemopexin During Purificationmentioning

confidence: 99%

“…Exposure of hemopexin to acidic pH has the potential to result in a number of chemical modifications to the structure of human hemopexin, so the acidic conditions involved in some precipitation methods or in elution from affinity resins are a concern. For example, human hemopexin is susceptible to hydrolysis in dilute acid (pH 2) 50 with the N-domain having most of the susceptible peptide bonds 63 ;…”

Section: Potential Chemical and Structural Modification Of Hemopexinmentioning

confidence: 99%

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An alternative view of the proposed alternative activities of hemopexin

2011

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Hemopexin is a plasma protein that plays a well-established biological role in sequestering heme that is released into the plasma from hemoglobin and myoglobin as the result of intravascular or extravascular hemolysis as well as from skeletal muscle trauma or neuromuscular disease. In recent years, a variety of additional biological activities have been attributed to hemopexin, for example, hyaluronidase activity, serine protease activity, proinflammatory and anti-inflammatory activity as well as suppression of lymphocyte necrosis, inhibition of cellular adhesion, and binding of divalent metal ions. This review examines the challenges involved in the purification of hemopexin from plasma and in the recombinant expression of hemopexin and evaluates the questions that these challenges and the characteristics of hemopexin raise concerning the validity of many of the new activities proposed for this protein. As well, an homology model of the three-dimensional structure of human hemopexin is used to reveal that the protein lacks the catalytic triad that is characteristic of many serine proteases but that hemopexin possesses two highly exposed Arg-Gly-Glu sequences that may promote interaction with cell surfaces.

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“…Recently, MMP-19 has been reported to be associated with the surfaces of myeloid cells, and the PEX in MMP-19 appears to be critical for this association (Mauch et al, 2002). The complete primary structure of human hemopexin was determined by Takahashi et al (Takahashi et al, 1985). The structural similarities between hemopexin and MMPs have been pointed out; the MMP C-terminal domains all have 4-stranded, anti-parallel b-sheets arranged around a central axis and are members of a wider fold family known as the b-propeller fold, first seen in the structure of hemopexin (Bode, 1995;Li et al, 1995;Faber et al, 1995;Crennell et al, 2000).…”

Section: +mentioning

confidence: 99%

Inhibition of Mg2+-dependent Adhesion of Polymorphonuclear Leukocytes by Serum Hemopexin: Differences in Divalent-Cation Dependency of Cell Adhesion in the Presence and Absence of Serum

Suzuki

Kobayashi

Doi

et al. 2003

Cell Struct. Funct.

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ABSTRACT. Circulating and nonadherent polymorphonuclear leukocytes (PMNs) become activated to attain adhesive state in an integrin-dependent manner by various stimuli, and perform a variety of microbicidal functions such as phagocytosis and superoxide production. We found that, in the absence of serum, a physiological concentration of hemopexin has a strong inhibitory action on Mg 2+ -dependent adhesion of PMA-activated PMNs to fibrinogen-and serum-coated surfaces. Under these conditions, Ca 2+ had no effect on Mg 2+ -dependent adhesion or the adhesion-inhibitory activity of hemopexin. In contrast, PMNs suspended in serum containing sufficient amounts of hemopexin to inhibit adhesion showed marked adherence, which was inhibited by EGTA. Next, we prepared a small-molecule fraction of serum by ultrafiltration followed by boiling. PMA-activated PMNs was found to adhere in the presence of both hemopexin and the small-molecule fraction, and the adhesion was enhanced by exogenous Ca 2+ . EGTA abolished the effect of the small molecule fraction. The data suggest that serum contains adhesion-promoting factor(s) which allows PMNs to adhere despite the presence of hemopexin and that Ca 2+ is required for adhesion-promoting activity. Further study of hemopexin may provide clues for new therapeutic strategies aimed at interfering with PMN adhesion to control inflammation and tissue injury.

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Complete amino acid sequence of human hemopexin, the heme-binding protein of serum.

Abstract: BiochemistryComplete amino acid sequence of human hemopexin, the hemebinding protein of serum (protein

Cited by 99 publications

References 16 publications

Diagnostic Value of the Hemopexin N-Glycan Profile in Hepatocellular Carcinoma Patients

Diagnostic Value of the Hemopexin N-Glycan Profile in Hepatocellular Carcinoma Patients

An alternative view of the proposed alternative activities of hemopexin

Inhibition of Mg2+-dependent Adhesion of Polymorphonuclear Leukocytes by Serum Hemopexin: Differences in Divalent-Cation Dependency of Cell Adhesion in the Presence and Absence of Serum

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