Biological Sciences: Amino-acid Sequence of the Carboxyl Terminal Octapeptide of Human Haptoglobin β Chain

Barnett, Don R.; Lee, Tong-Ho; Bowman, Barbara H.

doi:10.1038/225938a0

Cited by 25 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An arginine residue was deduced between the a-and s-chain sequences that serves as a site for limited proteolysis leading to the lormation of the a and 6 polypeptides in mature haptoglobin. This finding strengthened the evolutionary homology previously observed in haptoglobin and the serine prcteases (6,7). An additional evolutionary point was 2FS iF is revealed ir the sequence of cDNA encoding Hpa S. The a and a domains in the Hpa FS gene were found, as expected, to differ in the codons for the 53rd residue (lysine, AAG, in the a F domain) and the 112th residue (glutamic acid, GAG in the a S domain).…”

Section: Introductionsupporting

confidence: 90%

Evolution of haptoglobin: comparison of complementary DNA encodingHpα^1SandHpα^2FS

et al. 1984

Self Cite

View full text Add to dashboard Cite

Haptoglobin is a transport glycoprotein which removes free hemoglobin from the circulation of vertebrates. In human populations haptoglobin is polymorphic due to three alleles, Hp alpha 1F, Hp alpha 1S and Hp alpha 2. The Hp alpha 2 allele is roughly twice the length of the Hp alpha 1 alleles and is the product of a partial gene duplication possibly resulting from an unequal crossover event in a heterozygous genotype Hp alpha 1F/Hp alpha 1S. In the study described here we compare the cDNA encoding Hp alpha 1S to that encoding Hp alpha 2FS . Both have a leader sequence followed by the genotypic alpha chain sequence, a beta sequence and an untranslated sequence in the 3' end. The cDNA encoding Hp alpha 2FS is composed of alpha 1F and alpha 1S domains differing by four nucleotide replacements. Hp alpha 1S cDNA contains the same replacement site mutations found in the alpha 1S domain of Hp alpha 2FS , indicating that this coding region has sustained few, if any, mutations since its incorporation into the Hp alpha 2FS gene.

show abstract

Section: Introductionsupporting

confidence: 90%

Evolution of haptoglobin: comparison of complementary DNA encodingHpα^1SandHpα^2FS

et al. 1984

Self Cite

View full text Add to dashboard Cite

show abstract

“…CNBr V must represent the carboxyl-terminal fragment, since it contained no homoserine or homoserine lactone and yielded results (0.4 mol of Asn/mol of CNBr V) after CPA hydrolysis which were identical to CPA hydrolyses of intact 13 chain. Further evidence for carboxyl-terminal asparagine was provided by Barnett et al (1970Barnett et al ( , 1972). In addition, tryptic peptides of intact /3 chain have also provided overlapping sequences in agreement with those reported in Figure 8 (Kurosky, Rasco, and Bowman, to be published; Barnett, 1971).…”

Section: Discussionmentioning

confidence: 93%

“…Some sequence similarity between the a chain of haptoglobin and immunoglobulin light chains was presented to support this comparison (Black and Dixon, 1968). Sequence studies of the 8 chain, however, revealed considerable similarity to the chymotrypsin family of serine proteases (Barnett et al, 1970(Barnett et al, , 1972Kurosky et al, 1974a,b).…”

mentioning

confidence: 93%

Characterization of the cyanogen bromide fragments of the β chain of human haptoglobin

Kurosky¹,

Hay²,

Kim³

et al. 1976

Biochemistry

Self Cite

View full text Add to dashboard Cite

Characterization of the cyanogen bromide (CNBr) fragments of the beta chain of human haptoglobin revealed five major fragments resulting from cleavage of four methionyl residues. The fragments were isolated by gel filtration in guanidine-HCl on Sepharose 6B and Bio-Gel P10 and P60. Compositional analyses of the five cyanogen bromide fragments accounted for 248-253 amino acid residues in agreement with the number of residues determined for the intact beta chain. Most of the carbohydrate was attached to CNBr II. Automated amino-terminal sequence analysis and carboxyl-terminal hydrolysis with carboxypeptidase of the haptoglobin beta chain and cyanogen bromide fragments identified 139 residues, or about 55% of the beta-chain molecule. The placement of the fragments within the beta-chain molecule was established by sequence analysis of whole beta chain and a plasmin cleavage fragment. The position of CNBr V was confirmed by the absence of homoserine or homoserine lactone. Cyanogen bromide reaction of intact haptoglobin 1-1 resulted in the isolation of a beta-chain fragment, CNBr III, covalently attached to the intact alpha1 chain by a single disulfide bond. The beta chain was shown to have primary structural similarities to the chymotrypsin family of serin eproteases. Partial sequence analysis of CNBr V established the region which is comparable to the serine-195 active-site region: /Asp-Thr-Cys-Tyr-Gly-Asp-Ala-Gly-Ser-Ala-Phe/ (residues 189-199, chymotrypsinogen A numbering). The active-site serine-195 is replaced by alanine; however, the specificity residue of the trypsin-like enzymes, Asp-189, is preserved. Several minor cyanogen bromide cleavage products were also identified in yields of up to 15%. These minor cleavage products give evidence that tryptophanyl residues in proteins, or glycoproteins, are also susceptible to cyanogen bromide cleavage.

show abstract

“…The significance of this repeat is not known. Although haptoglobin has lost the capacity for proteolytic activity, there is strong similarity in sequences of the Hp,/ chain and serine proteases (6,7) and a weaker homology of the Hpa chain and activation peptides from serine proteases (7 (24) show a high degree of homology (Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

“…The alignment of the aiF and alS sequences in the a2 chain has eluded protein characterization and whether the Hpa2 chain is aligned Glu-53/Lys-112 or Lvs-53/Glu-112 has remained unknown. In the study of protein evolution, haptoglobin clearly descended from the phylogenetic tree of serine proteases (6,7) and, although it has lost the proteolytic activity characteristic of these enzymes, some key structural similarities are obvious (8).…”

mentioning

confidence: 99%

Identification and characterization of human haptoglobin cDNA.

Yang¹,

Brune²,

Baldwin³

et al. 1983

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

View full text Add to dashboard Cite

Recombinant plasmids containing human cDNA encoding haptoglobin, a plasma protein that binds free hemoglobin, have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Four cDNA clones containing inserts have been obtained .that span 1,218 nucleotides of the haptoglobin coding sequence, including the 3' end of the haptoglobin cDNA. The cDNA sequence included a leader sequence followed by a2-chain and fl-chain sequences. A heretofore unseen arginine residue was deduced between the human a-and fl-chain sequences. This is a probable site of limited proteolysis leading to the formation of the a and fi polypeptides in mature haptoglobin.A comparison of the haptoglobin a-p-junction region and the heavy-light-chain junction of tissue-type plasminogen activator strengthens the evolutionary homology found in haptoglobin and the serine proteases. The Hpa2 gene, which was shown earlier to be a partial duplication produced by unequal crossing-over between Hpal genes, has been impossible to align by protein characterization. The cDNA sequence establishes the alignment of Hpa2FS in the Hpa2 gene studied here.

show abstract

Biological Sciences: Amino-acid Sequence of the Carboxyl Terminal Octapeptide of Human Haptoglobin β Chain

Cited by 25 publications

References 10 publications

Evolution of haptoglobin: comparison of complementary DNA encodingHpα^1SandHpα^2FS

Evolution of haptoglobin: comparison of complementary DNA encodingHpα^1SandHpα^2FS

Characterization of the cyanogen bromide fragments of the β chain of human haptoglobin

Identification and characterization of human haptoglobin cDNA.

Contact Info

Product

Resources

About

Biological Sciences: Amino-acid Sequence of the Carboxyl Terminal Octapeptide of Human Haptoglobin β Chain

Cited by 25 publications

References 10 publications

Evolution of haptoglobin: comparison of complementary DNA encodingHpα1SandHpα2FS

Evolution of haptoglobin: comparison of complementary DNA encodingHpα1SandHpα2FS

Characterization of the cyanogen bromide fragments of the β chain of human haptoglobin

Identification and characterization of human haptoglobin cDNA.

Contact Info

Product

Resources

About

Evolution of haptoglobin: comparison of complementary DNA encodingHpα^1SandHpα^2FS

Evolution of haptoglobin: comparison of complementary DNA encodingHpα^1SandHpα^2FS