Hemoglobin Okayama [β‐2 (NA 2) His → Gln]: A new ‘silent’ hemoglobin variant with substituted amino acid residue at the 2,3‐diphosphoglycerate binding site

Harano, Teruo; Harano, Keiko; Shibata, Susumu; Ueda, Seinosuke; Mori, Hiroo; Arimasa, Naomichi

doi:10.1016/0014-5793(83)80239-7

Cited by 34 publications

(9 citation statements)

References 15 publications

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“…(23,24) that also results in an NH2-terminal elongated chain owing to the preservation of the initiator methionine. In contrast, the other known variants at the (2 site, Hb Deer Lodge (His Arg) (25) and Hb Okayama (His -> Gln) (26) (28). Na-acetyltransferases have been discovered in a variety of tissues (28)(29)(30)(31)(32) and do not display either cellular or phylogenetic specificity.…”

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confidence: 99%

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

Boissel¹,

Kasper²,

Shah³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

106

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The hemoglobin variant South Florida has been shown by protein sequencing and fast-atom-bombardment mass spectroscopy to have a substitution ofmethionine for the NH2-terminal valine of the (8-globin chain. In addition, there was complete retention of the initiator methionine on the mutant polypeptide. Approximately 20% of the protein was acetylated at the NH2 terminus of the (3 chain. A search of a comprehensive data bank of protein and gene sequences revealed 84 unrelated vertebrate proteins that have not undergone cleavage of leader sequences. A highly nonrandom distribution of residues at the NH2 termini of these proteins predicts removal of the initiator methionine as well as NH2-terminal acetylation. Proteins that undergo removal commonly have serine, alanine, glycine, or valine, as the NH2-terminal residues. The first three residues favor N-acetylation. Proteins that retain the initiator methionine commonly have a charged residue or methionine at the second position. Information on Hb South Florida and other hemoglobins coupled with this survey of primary sequence provides insights into the NH2-terminal processing of proteins.The biological properties of a large number of proteins are significantly altered by cotranslational and posttranslational modifications. In eukaryotes, the initiation of translation takes place at an AUG codon on mRNA (1). The NH2-terminal methionine residue is generally cleaved from the nascent polypeptide by an aminopeptidase (2). Soon thereafter the new NH2-terminal residue is often acetylated at the a-amino group (3,4). Only fragmentary information on NH2-terminal processing is available and, therefore, the molecular mechanism is still poorly understood. It has been suggested that cleavage of the initiator methionine is prevented when the adjacent residue is a charged amino acid (5). The MATERIALS AND METHODSPhosphate-free hemolysates (6) were prepared from heparinized blood samples. Hemolysate (1-2 g of hemoglobin) was analyzed on a column (5 x 22 cm) of Bio-Rex 70 (Bio-Rad) cation-exchange resin as described (7). The "Hb Al," fraction was dialyzed vs. 0.25 M ammonium acetate, pH 8.5, and rechromatographed on a column (2 x 6 cm) of Glycogel B boronate affinity resin (Pierce) (8). The non-retained Hb fraction from the affinity column and Hb A0 fraction from Bio-Rex chromatography were converted to globin by acid/acetone precipitation (9) and separated into a and /3 subunits by carboxymethyl-cellulose chromatography in 8 M urea. After aminoethylation (10), the isolated chains were digested with trypsin (11 Tryptic peptides were dissolved in 0.5% acetic acid/glycerol, 1:1 (vol/vol) solution. About 2 ,ug of the sample was applied per analysis.Abbreviations: FAB-MS, fast-atom-bombardment mass spectroscopy; RP-HPLC, reverse-phase HPLC. 8448The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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confidence: 99%

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

Boissel¹,

Kasper²,

Shah³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Several diabetic patients were reported to demonstrate unreasonably low HbA 1c values compared to their plasma glucose control,14–22 while others showed incorrectly high HbA 1c levels 23–28. Some rare Hb variants, such as Hb D, Hamaden, Himeji, Hoshida, North Manchester, Riyadh and Sagami, cause such low HbA 1c levels in the cation exchange HPLC-based assay,6 whereas other uncommon Hb variants, including Hb J, Graz, Niigata, Okayama, Old Dominion, Raleigh, Sherwood Forest, and South Florida, originate spuriously high HbA 1c in this assay method 6.…”

Section: Discussionmentioning

confidence: 99%

Identification of the First Japanese Family Harboring a Novel Hemoglobin Variant “Perpignan”, Which Caused Low HbA_1c Measurement During Diabetic Follow-Up

et al. 2011

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Hemoglobin A1c (HbA1c) is an important parameter for evaluating long-term (6–8 weeks) control of blood glucose levels in patients with diabetes mellitus. We report a Japanese diabetic case who harbored abnormal Hb and demonstrated falsely low HbA1c levels in the regular ion exchange HPLC-based assay. His abnormal β-globin chain had an amino acid replacement that corresponded to glycine to serine substitution at amino acid position 136 of the β-globin chain (Hb Perpignan). Accordingly, a heterozygotic point mutation replacing guanine by adenine at nucleotide position 406 (β136G > S) was identified in the β-globin gene of the proband and his son. These results indicate that the patient had Hb Perpignan, and this abnormal Hb interfered with the HPLC-based HbA1c assay commonly used in the clinic. The cases presented are the first report of patients in the Japanese population harboring Hb Perpignan (β136G > S).

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“…We used a commercially available HPLC for HbAac to screen the families for Hb Graz and Hb Sherwood Forest [4]. Previously unknown hemoglobin variants producing falsely elevated HbAlc values have been detected in individual patients and their families [6,8,14]. Previously unknown hemoglobin variants producing falsely elevated HbAlc values have been detected in individual patients and their families [6,8,14].…”

Section: Discussionmentioning

confidence: 99%

“…We report the occurrence of clinically silent W. J. Hb Okayama was previously identified in Japan in 1983 [8] and in Lower Austria in 1992 [6]. E. C. Reisinger 9 R. W. Lipp [17] and in Styria in 1992 [19].…”

Section: Introductionmentioning

confidence: 98%

Hemoglobin variants recently detected in Austria

et al. 1995

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Measurement of glycated hemoglobin (HbAtc) is used for routine management of diabetic patients. Glucose linkage to HbAtc reflects mean blood glucose levels during the last 3 months before examination. Various methods for HbA1c determination show abnormal values with hemoglobin variants. In some diabetic patients excessively high HbA1c values with high-performance liquid chromatography (HPLC) led to the detection of Hb Graz. In addition to Hb Graz, other silent hemoglobin variants have been found in Austria. Here we review Hb Graz, Hb Sherwood Forest, and Hb Okayama detected while using HPLC for the measurement of HbA1c in diabetic patients.

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Hemoglobin Okayama [β‐2 (NA 2) His → Gln]: A new ‘silent’ hemoglobin variant with substituted amino acid residue at the 2,3‐diphosphoglycerate binding site

Cited by 34 publications

References 15 publications

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

Identification of the First Japanese Family Harboring a Novel Hemoglobin Variant “Perpignan”, Which Caused Low HbA_1c Measurement During Diabetic Follow-Up

Hemoglobin variants recently detected in Austria

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Hemoglobin Okayama [β‐2 (NA 2) His → Gln]: A new ‘silent’ hemoglobin variant with substituted amino acid residue at the 2,3‐diphosphoglycerate binding site

Cited by 34 publications

References 15 publications

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

Identification of the First Japanese Family Harboring a Novel Hemoglobin Variant “Perpignan”, Which Caused Low HbA1c Measurement During Diabetic Follow-Up

Hemoglobin variants recently detected in Austria

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Identification of the First Japanese Family Harboring a Novel Hemoglobin Variant “Perpignan”, Which Caused Low HbA_1c Measurement During Diabetic Follow-Up