Haptoglobin-related protein (HPR)
The protein contains 348 amino acids for an estimated molecular weight of 39030 Da.
Primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL). This HDL particle, termed trypanosome lytic factor-1 (TLF-1), mediates human innate immune protection against many species of African trypanosomes. Binds hemoglobin with high affinity and may contribute to the clearance of cell-free hemoglobin to allow hepatic recycling of heme iron. (updated: Oct. 25, 2017)
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.
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Biological Process
Acute inflammatory response
Positive regulation of cell death
Receptor-mediated endocytosis
Response to organic substance
Zymogen activation
The reference OMIM entry for this protein is 140210
Haptoglobin-related protein gene; hpr
DESCRIPTION
The HPR gene is the product of a segmental duplication of the HP gene (140100) on chromosome 16. Like HP, HPR binds hemoglobin (Hb) with high affinity. Together with apolipoprotein L1 (APOL1; 603743), HPR-Hb forms a protein complex called trypanosome lytic factor-1 (TLF1), which plays an important role in protection against Trypanosoma brucei, the pathogen that causes trypanosomiasis, or sleeping sickness (summary by Hardwick et al., 2014).CLONING
Bensi et al. (1985) and Maeda (1985) isolated the human HPR gene. Its predicted amino acid sequence differs by about 8% from that of the electrophoretically fast-migrating HP variant (HP1F; 140100.0001). The differences appeared to be located on the surface of the protein molecule, and the regions and specific residues considered to be important for binding hemoglobin are identical in the HP and HPR proteins. Smithies and Powers (1986) found evidence of gene conversion (see 142200) between the closely linked HP and HPR loci.GENE STRUCTURE
Maeda and Kim (1990) demonstrated that the 2 genes in the human haptoglobin cluster, HP and HPR, contain 2 retrovirus-like elements. One (RTVL-Ia) is in the first intron of the HPR gene, and the second (RTVL-Ic) is at the 3-prime-end of the gene cluster. In the chimpanzee 3-gene cluster (HP-HPR-HPP), there is an additional retrovirus-like element (RTVL-Ib) in the intergenic region between the chimpanzee HPR and HPP loci. RTVL-Ia and RTVL-Ib are essentially full size and have the general structure 5-prime-LTR--gag--pol-env--3-prime-LTR, while RTVL-Ic lacks about one-third of its 5-prime portion. Although none of the elements had retained long open reading frames, Maeda and Kim (1990) detected stretches with amino acids identical to various parts of proteins of the Moloney murine leukemia virus (Mo-MuLV). They concluded that the RTVL-I elements were derived from a virus similar in structure to Mo-MuLV. The DNA sequences surrounding the insertion points of the 3 RTVL-I elements were dissimilar, implying that they integrated into the haptoglobin gene cluster independently at some time after the initial formation of the triplicated gene cluster in primates. Comparison of the nucleotide sequences of the 3 elements suggested that foreign DNA introduced into the genome can accumulate mutations more rapidly than the genomic sequences surrounding them. At least 5 other families of retrovirus-like sequences have been found in the human genome; for a review, see Cohen and Larsson (1988). In RTVL-I, the tRNA used for the primer binding site is ile-tRNA. (RTVL-I = retrovirus-like sequence--isoleucine.)MAPPING
The HPR gene maps to chromosome 16q22.1 (Bensi et al., 1985; Maeda, 1985). Maeda et al. (1986) found that the HPR gene(s) lie on the downstream side of the HP gene (140100).GENE FUNCTION
Using immobilized hemoglobin for affinity chromatography, Nielsen et al. (2006) showed that HPR could bind hemoglobin as efficiently as HP, and SDS-PAGE showed that HPR migrated as a 45-kD monomer and a 90-kD dimer. In contrast to HP, HPR did not promote high-affinity binding to CD163 (605545). Western blot analysis of 18 persons with normal HP levels and 13 patients with low HP levels resulting from sickle cell anemia and extensive intravascular hemolysis indicated that the plasma concentration of HPR was unaffected by hemolysis, suggesting that depletion of HP but not HPR in these patients may be a consequence of ... More on the omim web site
Feb. 10, 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 HPR
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 140210 was added.