| Primary Identifier | IPR008292 | Type | Family |
| Short Name | Haptoglobin |
| description | Haptoglobin is a plasma protein that binds haemoglobin. The resulting complex is too large to be excreted by the kidney, thereby preventing loss of iron and damage to the kidney. The haptoglobin-haemoglobin complex is degraded in the liver, which is also the site of haptoglobin synthesis. The mature haptoglobin molecule is a tetramer, consisting of two alpha and two beta chains. Alpha and beta chains arise from proteolytic processing of the same precursor. Each beta chain can bind an α-β heterodimer of haemoglobin so that each haptoglobin tetramer binds one haemoglobin tetramer. In Pan troglodytes (Chimpanzee), haptoglobin genes form a small multigene family of three genes: HP, HPR (haptoglobin-related protein, which may be non-functional), and HPP (haptoglobin-primate) []. In contrast, most humans have a two-gene cluster due to an unequal homologous crossover event between HPR and HPP in the human lineage []. Such events may be common among these closely related genes as Macaca mulatta (Rhesus macaque) was found to have haplotypes of one- or two-gene clusters that appear to have formed from unequal crossover among an ancestral three-gene cluster []. The haptoglobin precursor contains a signal sequence, a sushi domain (in mature alpha chain), and a trypsin domain (in mature beta chain) which belongs to the MEROPS peptidase family S1 (clan PA(S)). Haptoglobins have no enzymatic activity as the active site residues typical of trypsin-related proteases are not conserved, they are therefore classed as non-peptidase homologues. A common allelic variant in humans contains two sushi domains.Uncleaved haptoglobin is also known as zonulin, and plays a role in intestinal permeability []. |
