Nitrophorin domain (IPR002351)

Short name: Nitrophorin_domain

Overlapping homologous superfamilies

Domain relationships



Nitrophorins are haemoproteins found in saliva of blood-feeding insects [PMID: 10093938, PMID: 11058753]. Saliva of the blood-sucking bug Rhodnius prolixus (Triatomid bug) contains four homologous nitrophorins, designated NP1 to NP4 in order of their relative abundance in the glands [PMID: 7721773]. As isolated, nitrophorins contain nitric oxide (NO) ligated to the ferric (FeIII) haem iron. Histamine, which is released by the host in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site. Dilution, binding of histamine and increase in pH (from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.

The salivary nitrophorin from the hemipteran Cimex lectularius (Bed bug) has no sequence similarity to R. prolixus nitrophorins. It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent evolution [PMID: 9716517].

3-D structures of several nitrophorin complexes are known [PMID: 11058753]. The nitrophorin structures reveal lipocalin-like eight-stranded beta-barrel, three alpha-helices and two disulphide bonds, with haem inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin, in a similar fashion (see [PMID: 8761444] for review). The haem iron is ligated to His59. The position of His59 is restrained through water-mediated hydrogen bond to the carboxylate of Asp70. The His59-Fe bond is bent ~15 degrees out of the imidazole plane. Asp70 forms an unusual hydrogen bond with one of the haem propionates, suggesting the residue has an altered pKa. In NP1-histamine structure, the planes of His59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidised cytochrome b5.

This entry represents the nitrophorin structural domain.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0051381 histamine binding
GO:0070026 nitric oxide binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.