Haptoglobin (HP)
The protein contains 406 amino acids for an estimated molecular weight of 45205 Da.
As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity, and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.', 'The uncleaved form of allele alpha-2 (2-2), known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens. (updated: Nov. 7, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| allele HP*1F | |
| allele HP*1F | |
| AHP | |
| dbSNP:rs189115161 |
Biological Process
Acute inflammatory response
Acute-phase response
Defense response
Defense response to bacterium
Immune system process
Negative regulation of hydrogen peroxide catabolic process
Negative regulation of oxidoreductase activity
Neutrophil degranulation
Positive regulation of cell death
Receptor-mediated endocytosis
Response to hydrogen peroxide
Response to organic substance
Zymogen activation
The reference OMIM entry for this protein is 140100
Haptoglobin; hp haptoglobin, alpha polypeptide, included
Haptoglobin, beta polypeptide, included
Bp, included
DESCRIPTION
Haptoglobin (HP), a plasma glycoprotein that binds free hemoglobin (see 141800), has a tetrameric structure of 2 alpha and 2 beta polypeptides that are covalently associated by disulfide bonds. In human populations, there are 3 common genetic haptoglobin types, Hp1 (140100.0001), Hp2 (140100.0002), and the heterozygous phenotype Hp2-1, reflecting inherited variations in the HP polypeptides (summary by Yang et al., 1983).CLONING
Two loci had been thought to be involved in haptoglobin synthesis, 1 for alpha chains and 1 for beta chains. The findings of Haugen et al. (1981) indicated that the alpha and beta chains are encoded by a single gene. They studied de novo biosynthesis of haptoglobin in a rabbit reticulocyte cell-free translation system using mRNA preparations from the livers of turpentine-treated rats. Analysis of the translation mixtures with antiserum specific for the alpha subunit, the beta subunit, or the native heterotetramer always resulted in recovery of a single protein with molecular mass about 38.0 kD, which on cyanogen bromide or trypsin digestion broke down into small peptic fragments that reacted specifically with either anti-alpha or anti-beta antibodies. The authors concluded that the primary translation product of haptoglobin mRNA is a single polypeptide that contains the elements of both the alpha and the beta subunits. Haptoglobin is synthesized as a single precursor protein that is proteolytically processed after translation to form the dissimilar alpha and beta subunits. Black and Dixon (1968) reported the amino acid sequences of the alpha chains of haptoglobin. There are similarities between the primary structures of the alpha chain and of light chains of gamma globulins; there are also functional homologies since both form complexes with specific proteins. A common evolutionary origin was postulated. Amino acid sequence data were summarized by Dayhoff (1972). According to amino acid sequence data, haptoglobin is homologous to serine proteases of the chymotrypsinogen family (Kurosky et al., 1980). Yang et al. (1983) isolated recombinant plasmids containing cDNA coding for haptoglobin by screening an adult human liver library with a mixed oligonucleotide probe. A hitherto unknown arginine residue was deduced between the alpha and beta sequences, which was the probable site of the limited proteolysis that leads to the formation of the separate alpha and beta polypeptides of mature haptoglobin. Comparison of the haptoglobin alpha-beta junction region with the heavy-light-chain junction of tissue-type plasminogen activator strengthens the evolutionary homology of haptoglobin and serine proteases.GENE FUNCTION
The alpha-2 chain is not found in any species but man. Black and Dixon (1968) suggested that alpha-2 chains give a selective advantage because their increased size reduces loss of the haptoglobin-hemoglobin complex by the kidney and at the same time hemoglobin binding is unimpaired and heme degradation enhanced. Haptoglobin protects against the potentiation of bacterial growth by hemoglobin (Eaton et al., 1982); herein might lie a basis for polymorphism. A major function of haptoglobin is to bind hemoglobin (Hb) to form a stable Hp-Hb complex and thereby prevent Hb-induced oxidative tissue damage. Clearance of the Hp-Hb complex can be mediated by the monocyte/macrophage scavenger receptor CD163 (605545). Asleh et al. (2003) assessed the scavenging function of Hp ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for HP
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 140100 was added.