Protein Domain : Tick histamine-binding protein IPR002970

Type	Family
Description	The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteinsdisplaying high specificity for small hydrophobic molecules [ , ]. Functionsof these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration and the enzymatic synthesis of prostaglandins.The crystal structures of several lipocalins have been solved and show a novel 8-stranded anti-parallel β-barrel fold well conserved within the family. Sequence similarity within the family is at a much lower level andwould seem to be restricted to conserved disulphides and 3 motifs, which form a juxtaposed cluster that may act as a common cell surface receptorsite [ ]. By contrast, at the more variable end of the fold are found an internal ligand binding site and a putative surface for the formation of macromolecular complexes []. The anti-parallel β-barrel fold is alsoexploited by the fatty acid-binding proteins (which function similarly by binding small hydrophobic molecules), by avidin and the closely relatedmetalloprotease inhibitors, and by triabin. Similarity at the sequence level, however, is less obvious, being confined to a single short N-terminal motif. The lipocalin family can be subdivided into kernal and outlier sets. Thekernal lipocalins form the largest self-consistent group, comprising the subfamily of tick histamine-binding proteins. The outlier lipocalins form several smaller distinct subgroups: the OBPs, the von Ebner's gland proteins, alpha-1-acid glycoproteins, tick histamine binding proteins and the nitrophorins. The tick histamine binding proteins are the most recently identified set of outlier lipocalins. The structure of one tick histamine binding protein hasbeen solved [ ] and has shown the proteins to have the characteristic lipocalin fold but without any appreciable sequence similarity. The tick histamine binding proteins are secreted into the saliva of the ixodid tick Rhipicephalus appendiculatus and share functional similarity with the nitrophorins, sequestering histamine at the wound site. Because the tickhistamine binding proteins outcompete histamine receptors, they are able to overcome host inflammatory and immune responses. This enables the ticks tofeed for extended periods, lasting from days to several weeks, and are able to gorge themselves on large blood meals increasing their body mass 100 fold.Unlike nitrophorins, the tick proteins do not bind haem (or other cofactor), but ligate histamine directly in two rigid orthogonally-arranged binding sites, at opposing ends of the lipocalin anti-parallel β-barrel, which have an unusually polar character.
Short Name	Tick_his-bd