Amino acid sequence of human histidine-rich glycoprotein derived from the nucleotide sequence of its cDNA

Koide, Takao; Foster, Donald C.; Yoshitake, Shinji; Davie, Earl W.

doi:10.1021/bi00356a055

Cited by 170 publications

(145 citation statements)

References 45 publications

(55 reference statements)

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“…This value is in agreement with the molecular weight calculated for human plasma HPRG free of carbohydrate on the basis of its amino acid composition (Heimburger et al 1972;Koide et al 1986). The minor components that give rise to unresolved faint bands of higher molecular weight (55-75 kD) in our plasma immunoblot are probably related to the heterogeneity of HPRG forms with respect to carbohydrate attachment.…”

Section: Discussionsupporting

confidence: 89%

“…N-terminal sequence analysis of the fragments liberated by limited proteolysis revealed a striking similarity of this protein to rabbit plasma HPRG (Borza et al 1996) although, in comparison with mature HPRG, the AMP deaminase-associated variant probably contains a unique N-terminal extension. Among the 60 amino acids sequenced up to now in the novel HPRG isoform, four substitutions were found with respect to the published rabbit HPRG sequence, all of them localized in the 472-477 region that also differs in five amino acid residues compared with the homologous region of the human protein (residues 461-466) (Koide et al 1986). This divergence enabled us to raise a rabbit antibody against a synthetic peptide equivalent to residues 462-471 of human plasma HPRG.…”

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confidence: 96%

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Presence in Human Skeletal Muscle of an AMP Deaminase-associated Protein That Reacts with an Antibody to Human Plasma Histidine-Proline-rich Glycoprotein

Sabbatini

Ranieri-Raggi

Pollina

et al. 1999

J Histochem Cytochem.

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SUMMARY Histidine-proline-rich glycoprotein (HPRG) is a protein that is synthesized by parenchimal liver cells. The protein has been implicated in a number of plasma-specific processes, including blood coagulation and fibrinolysis. We have recently reported the association of an HPRG-like protein with rabbit skeletal muscle AMP deaminase (AMPD). The results of the immunological analysis reported here demonstrate that an antibody against human plasma HPRG reacts with an AMPD preparation from human skeletal muscle. To probe the localization of the putative HPRG-like protein in human skeletal muscle, serial sections from frozen biopsy specimens were processed for immunohistochemical and histoenzymatic stains. A selective binding of the anti-HPRG antibody to Type IIB muscle fibers was detected, suggesting a preferential association of the novel protein to the AMPD isoenzyme contained in the fast-twitch glycolytic fibers. Histidine-proline-rich glycoprotein (HPRG) is a protein present at a relatively high concentration in the plasma of vertebrates. Its specific function remains unclear, although it has been implicated in several phenomena, including blood coagulation and fibrinolysis (Peterson et al. 1987). In a recent article we reported the isolation from purified rabbit skeletal muscle AMP deaminase (AMPD) of an approximately 75 kD novel peptide with an amino acid composition significantly different from that derived from the available AMPD cDNAs (Ranieri-Raggi et al. 1997). N-terminal sequence analysis of the fragments liberated by limited proteolysis revealed a striking similarity of this protein to rabbit plasma HPRG (Borza et al. 1996) although, in comparison with mature HPRG, the AMP deaminase-associated variant probably contains a unique N-terminal extension. Among the 60 amino acids sequenced up to now in the novel HPRG isoform, four substitutions were found with respect to the published rabbit HPRG sequence, all of them localized in the 472-477 region that also differs in five amino acid residues compared with the homologous region of the human protein (residues 461-466) (Koide et al. 1986). This divergence enabled us to raise a rabbit antibody against a synthetic peptide equivalent to residues 462-471 of human plasma HPRG. The similarity between the 461-466 region of human plasma HPRG (S-F-P-L-P-H) and the corresponding sequence of the HPRG-like molecule isolated from rabbit skeletal muscle (S-F-S-L-R-H) prompted us to utilize the antibody to probe the immunohistochemical localization of the putative HPRG-like protein in human skeletal muscle. The experimental results show that the anti-HPRG antibody reacts with an AMPD preparation from human skeletal muscle. Moreover, a clear positive reaction was detected at the level of Type IIB fibers, giving evidence of the presence of an HPRGlike peptide in human skeletal muscle. These observations suggest a correlation of this protein as well as Correspondence to: Prof.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 96%

Presence in Human Skeletal Muscle of an AMP Deaminase-associated Protein That Reacts with an Antibody to Human Plasma Histidine-Proline-rich Glycoprotein

Sabbatini

Ranieri-Raggi

Pollina

et al. 1999

J Histochem Cytochem.

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“…8,16 The helix of HRG could mimic the positively charged helical regions of the antithrombin heparin-binding site. 36 Helical regions that bind to heparin are found in other proteins such as the protease nexin-1.…”

Section: Discussionmentioning

confidence: 99%

“…15 The N-terminal domains of HRG also bear similarity to the N-terminal region of antithrombin III, where the respective domains of both proteins are implicated in heparin binding. 16 This and the fact that both HRG and antithrombin III regulate thrombin activity by competing with one another for binding to heparin 17 points toward an evolutionary relationship between the 2 proteins. The N1 and N2 terminal domains of HRG are also implicated in the control of immune functioning through interactions with C1q, IgG, and FcgRI.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation

Kassaar¹,

McMahon

Thompson³

et al. 2014

Blood

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Key Points• The x-ray crystal structure of the N2 domain from HRG at 1.93Å resolution is presented.• The structure reveals an S-glutathionyl adduct at Cys185, which has implications for angiogenic regulation.Histidine-rich glycoprotein (HRG) is a plasma protein consisting of 6 distinct functional domains and is an important regulator of key cardiovascular processes, including angiogenesis and coagulation. The protein is composed of 2 N-terminal domains (N1 and N2), 2 proline-rich regions (PRR1 and PRR2) that flank a histidine-rich region (HRR), and a C-terminal domain. To date, structural information of HRG has largely come from sequence analysis and spectroscopic studies. It is thought that an HRG fragment containing the HRR, released via plasmin-mediated cleavage, acts as a negative regulator of angiogenesis in vivo. However, its release also requires cleavage of a disulphide bond suggesting that its activity is mediated by a redox process. Here, we present a 1.93Å resolution crystal structure of the N2 domain of serum-purified rabbit HRG. The structure confirms that the N2 domain, which along with the N1 domain, forms an important molecular interaction site on HRG, possesses a cystatin-like fold composed of a 5-stranded antiparallel b-sheet wrapped around a 5-turn a-helix. A native N-linked glycosylation site was identified at Asn184. Moreover, the structure reveals the presence of an S-glutathionyl adduct at Cys185, which has implications for the redox-mediated release of the antiangiogenic cleavage product from HRG. (Blood. 2014;123(12):1948-1955 Introduction Histidine-rich glycoprotein (HRG) is a plasma protein that regulates angiogenesis, coagulation, and immune function in vertebrates. Human HRG has an approximate mass of 70 kDa and is present in plasma at low micromolar concentrations (ca ;1.5 mM). The protein is arranged into 6 domains: 2 N-terminal domains (N1 and N2), a central histidine-rich region (HRR) flanked by 2 proline rich regions (PRR1 and PRR2), and a C-terminal domain (C). The N1, N2, and C domains are highly conserved between species, as is an arrangement of 6 disulfide bridges (Figure 1). In plasma, HRG binds to and regulates the function of a diverse variety of targets that include fibrinogen, plasminogen, thrombospondin, immunoglobulin G (IgG), complement factors, and heparin as well as cell-surface molecules such as Fcg receptors and heparan sulfate.1-9 HRG binds divalent metal cations within the HRR. 10 In particular, Zn 21 is known to bind this region and can modulate HRG activity by altering the protein's affinity for other targets. 11HRG is heavily glycosylated; the human protein has 6 putative N-linked glycosylation sites.11 The histidine-and proline-rich regions are predicted to be intrinsically disordered but N1, N2, and the C-terminal domains are likely to have ordered structures. The N1 and N2 domains share a high degree of sequence similarity to members of the cystatin superfamily of cysteine protease inhibitors.12 Type 1 cystatins (also known as stefins) are characterized b...

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“…Furthermore, the sequence around the last cysteine in bovine glu-ser-cys-pro-gly-thr (Sorensen et al, 1993) and human glu-ser-cys-pro-gly-lys (Koide et al, 1986) histidine-rich glycoprotein is also similar.…”

Section: The Q W a G Sequencementioning

confidence: 89%

Friends and relations of the cystatin superfamily—new members and their evolution

1997

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The cystatin "superfamily" encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never aquired this inhibitory activity. In recent years, several new members of the superfamily have been characterized, including proteins from insects and plants. Based on partial amino acid homology, new members, such as the invariant chain (Ii), and the transforming growth factor+ receptor type I1 (TGF-/3 receptor 11) may, in fact, represent members of an emerging family within the superfamily that may have used some common building blocks to form functionally diverse proteins. Cystatin superfamily members have been found throughout evolution and members of each family of the superfamily are present in mammals today. In this review, the new and older, established members of the family are arranged into a possible evolutionary order, based on sequence homology and functional similarities.Keywords: cystatins; cysteine protease inhibitors; evolution; fetuins; kininogens; TGF-/3 receptor I1The concept of a cystatin "superfamily" emerged in the early 1980s, precipitated by an observation that multiple cystatin-like sequences were present in the kininogens and that the stefins were related to both the cystatins and the repeats in the kininogens (Ohkubo et al., 1984). The cystatins are a family of cysteine protease inhibitors with homology to chicken cystatin (Barrett, 1981). Cystatins typically comprise = 1 15 amino acids, are largely acidic, contain four conserved cysteine residues known to form two disulfide bonds (Grubb et a]., 1984), may be glycosylated and/or phosphorylated, and contain a series of conserved residues, most notably the "QVVAG' sequence (reviewed in Rawlings & Barrett, 1990;Turk & Bode, 1991).Protein, cDNA, and genomic sequences of several cystatins have since been reported (e.g., Tsai et al., 1996; reviewed in Rawlings & Barrett, 1990;Turk & Bode, 1991). Their structural genes comprise three exons of characteristic size (e.g., Huh et al., 1995) (Fig. I), and a cluster of these genes is located on human chromosome 20 (e.g., Thiesse et al., 1994) although cystatin genes are also found on other chromosomes (e.g., Pennachio et al., 1996).Cystatin-like sequences identified in the kininogens (Ohkubo et al., 1984) were found to be present as sequence duplications. Subsequently, it was proposed that there were three cystatin-like repeats in the kininogen sequence, the amino terminal repeat being Reprint requests to: K.M Dziegielewska, Department of Anatomy and Physiology, University of Tasmania, GPO Box 252-24, Hobart, Tasmania 7001, Australia. less conserved (Salvesen et al., 1986). This threefold repeat is reflected in the triplicated gene structure (Kitamura et al., 1985). which has been shown to be common to the kininogens (e.g., Cole & Schreiber, 1992). Each of the three cystatin repeats is encoded by three exons of characteristic size (e.g., Cole & Schreiber, 1992).Thus, by the late 1980s the superfa...

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Amino acid sequence of human histidine-rich glycoprotein derived from the nucleotide sequence of its cDNA

Cited by 170 publications

References 45 publications

Presence in Human Skeletal Muscle of an AMP Deaminase-associated Protein That Reacts with an Antibody to Human Plasma Histidine-Proline-rich Glycoprotein

Presence in Human Skeletal Muscle of an AMP Deaminase-associated Protein That Reacts with an Antibody to Human Plasma Histidine-Proline-rich Glycoprotein

Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation

Friends and relations of the cystatin superfamily—new members and their evolution

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