Pentraxins (earlier also termed pentaxins), named for their homopentameric quaternary structure, are a superfamily of multifunctional conserved proteins that are characterized by a cyclic multimeric structure and by the presence in their carboxyl-terminal of an ~200 aa-long conserved domain, called pentraxin (PTX) domain. In addition, all the members of this family share an 8 aa-long conserved sequence (HxCxS/TWxS, in which x is any amino acid) in the pentraxin domain, called pentraxin signature. Some pentraxins, together with collectins and ficolins, constitute the humoral arm of innate immunity and behave as functional ancestors of Abs by mediating agglutination, complement activation, and opsonisation [1,2,3]. They are divided into short:

• C-reactive protein (CRP), a protein which, in mammals, is expressed during acute phase response to tissue injury or inflammation. CRP displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. CRPs have also been sequenced in an invertebrate, the Atlantic horseshoe crab, where they are a normal constituent of the hemolymph.
• Serum Amyloid P-component (SAP), a precursor of amyloid component P which is found in basement membrane and is associated with amyloid deposits.
• Hamster female protein (FP), a plasma protein whose concentration is altered by sex steroids and stimuli that elicit an acute phase response.

and long pentraxins:

• Human PTX3 (or TSG-14). PTX3 is a cytokine-induced protein.
• Vertebrate PTX4 [3].
• Guinea pig apexin [4], a sperm acrosomal protein. Apexin seems to be the ortholog of human neuronal pentraxin II (gene NPTX2) [5].
• Rat neuronal pentraxin I [6].

The pentraxin domain has also been found in multidomain proteins, such as:

• Mammalian polydom, an extracellular protein which includes an N-terminal von Willebrand factor A domain (see <PDOC50234>), hyalin repeats (HYRs) (see <PDOC50825>), epidermal growth factor repeats (EGFs) (see <PDOC00021>), sushi domains (see <PDOC50923>), and a single pentraxin domain.
• Vertebrate adhesion G-protein–coupled receptors (GPRs), in particular GPR144, GPR112, and GPR126.

The function of these proteins has not been defined yet, nor has the role of the pentraxin domain in multidomain proteins.

The pentraxin domain consists of two anti-parallel β-sheets in the form of a flattened β-barrel with a jellyroll topology (see <PDB:3KQR>) [7,8].

The pentraxin domain is related to the laminin G (LamG) (see <PDOC50025>) and thrombospondin N-terminal (TspN) domains [10].

The sequences of the different members of this family are quite conserved. As a signature, we selected a six residue pattern which includes a cysteine known to be involved in a disulfide bridge in CRPs and SAP. We have also developed a profile that covers the entire pentraxin domain.