HPR Human

Haptoglobin-related protein (HPR) is a fascinating molecule with significant roles in human biology. It is closely related to haptoglobin (HP), a well-known acute-phase plasma glycoprotein. HPR is encoded by the HPR gene, which is located on the long arm of chromosome 16 in humans .

Haptoglobin was first discovered in 1938 by French biochemists Max-Fernand Jayle and Michel Polonovski as a “plasma substance” that binds hemoglobin . The gene encoding haptoglobin, later denoted as HP or Hp, was identified by British biochemist Oliver Smithies and his mentor, Canadian geneticist Norma Ford Walker, in 1956 . They discovered that the gene could exist in two allelic forms, Hp1 and Hp2 .

In 1983, Italian geneticist Riccardo Cortese and his team sequenced the human Hp gene and discovered a closely related gene in its vicinity, which was later identified as the HPR gene . The HPR gene originated from the duplication of the HP gene and is present 2.2 kilobase pairs downstream of the HP gene on chromosome 16 . The HPR gene shares 94% similarity in DNA sequence with the HP gene .

Haptoglobin-related protein is a serum protein that binds to hemoglobin of red blood cells and is present only in primates . It acts as a molecule of innate immunity in association with apolipoprotein L1 (ApoL1)-containing high-density lipoprotein (HDL) particles . In humans, HPR, together with haptoglobin, acts as a cell-killing agent as part of the trypanolytic factor against the protozoan parasite Trypanosoma brucei, thereby providing natural resistance to African sleeping sickness .

HPR plays a crucial role in the innate immune system. It binds to hemoglobin released during intravascular hemolysis, forming a complex that is recognized and cleared by the macrophage scavenger receptor CD163 . This process protects the body from the toxic effects of free hemoglobin and elicits an anti-inflammatory response .

In addition to its role in hemoglobin scavenging, HPR is involved in a sophisticated immune defense mechanism against certain trypanosome parasites. The trypanosomal haptoglobin-hemoglobin receptor, evolved to supply the parasite with heme, also takes up the complex of hemoglobin and the HDL-bound HPR . This tricks the parasite into internalizing another HDL-associated protein and toxin, apolipoprotein L-I, which kills the parasite .