This project report is on Haptoglobin (Hp), which is a serum protein recognized for its capability to form a tight complex with hemoglobin (Hb) and thus suppressing the oxidative activity of Hb. Some topics studied in this project are: Protein secretion, Glycosylation, Gene duplications, Haptoglobin, Biosynthesis, etc.
Mammalian Hp is synthesized as a precursor (proHp) which goes through proteolytic cleavage by a formerly unknown enzyme in the endoplasmic reticulum (ER). In this research, a proHp-cleaving enzyme was singled out from human serum and labeled as complement C1r-like protein (C1rLP). Co-expression of C1rLP with proHp in mammalian cells led to cleavage of the latter protein in the ER. Mutation of either the active site serine residue in C1rLP or the arginine residue in the cleavage site of Hp eliminated the cleavage of proHp by C1rLP. RNAi tests in mammalian cells determined the proHp-cleaving enzyme as C1rLP. Hp continues to be present in all mammals examined up to now however its existence in non-mammalian species hasn’t been unambiguously proven. By searching presently available genomic DNA and cDNA sequence databases, a gene orthologous to mammalian Hp was discovered in bony fish. Hp-like protein expressed from this gene was proven to be a significant Hb protein in fish serum. Interestingly, no Hp-like gene was discovered in the genomes of either frog or chicken. In chicken, a protein in the past referred to as Hp was identified as PIT54, a member of a scavenger receptor cysteine-rich family of proteins.
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Contents
Introduction
1 Protein secretion
1.1 An overview
1.2 Protein transport within the secretory pathway
1.3 Post-translational modifications
1.3.1 Disulfide bond formation
1.3.2 Glycosylation
1.3.3 Endoproteolytic maturation of secretory proteins
1.3.4 Other modifications
1.4 Quality control in the secretory pathway
2 Evolution of genes and proteins
2.1 Gene duplications
2.2 Exon shuffling
3 Haptoglobin
3.1 Biosynthesis
3.2 Structure
3.3 Function
3.3.1 Binding to Hb
3.3.2 The role of Hp in the immune system
3.3.3 Other functions
3.3.4 Hp serotypes in disease
3.4 Hp in non-human species
3.4.1 Haptoglobin in fish
3.4.2 Avian haptoglobin
3.4.3 Mammalian haptoglobins
3.5 Hp-related protein
Present investigation
Work objectives
Paper I
Paper II
Paper III
Discussion
Proteolytic processing of Hp……..
Source: Uppsala University Library
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