Although invertebrates lack the complex clotting factor
cascade found in higher vertebrates, they do possess homologs of many
of the proteins essential for clotting in vertebrates.
Although invertebrates lack the complex clotting factor cascade found
in higher vertebrates, there are fibrinogen-like molecules, in both vertebrates
and invertebrates, including a group known as lectins (Xu and Doolittle,
1990). Invertebrate lectins can recognize carbohydrate groups on bacteria
and cause the agglutination of bacteria (Adema, 1997; Gokudan, 1999; Kairies,
2001). Vertebrates, including humans, also possess homologues of fibrinogen
which function in innate immunity (called ficolins) which recognize carbohydrate
groups on bacteria. Human ficolins bind the same molecules as some invertebrate
lectins (such as tachylectin 5A) and are more closely related to tachylectins
than to fibrinogen (Kairies, 2001).
Thrombin belongs to a family of proteins known as serine proteases. This
is an ancient gene family, including eubacterial digestive enzymes and
the vertebrate digestive enzymes trypsin and chymotrypsin. Most of these
proteins possess the amino acid proline at residue 225 in the protein.
However, in vertebrates, some of these proteins possess the amino acid
serine at residue 225. The change in some of the serine proteases needed
to acquire a function in coagulation seems to stem from one ancestral
mutation changing the amino acid at residue 225 (Guinto,1998; Dang, 1996).
This change enabled the binding of sodium and novel protein functions.
Some serine proteases in blood (such as plasmin and clotting factor XIa)
possess proline at site 225 while others such as thrombin, clotting factor
Xa (involved in clotting), and complement protein C1r (involved in immunity)
possess serine. Mutations at site 225 drastically affect the function
of thrombin (changing ligand recognition up to 60,000 fold).
When blood clots, several clotting factors and several proteins involved
in the regulation of coagulation perform a reaction converting the amino
acid glutamate to -carboxyglutamate (Gla) after translation. Not only
is this reaction essential for blood clotting (where it was first discovered),
it also has other functions in vertebrates and occurs in several bone
proteins, for example. This reaction and the enzyme which catalyzes it
( -glutamyl carboxylase) were thought to be found only in vertebrates.
It is now known in insects and molluscs as well where -carboxylation of
glutamate has several roles, such as the production of venom peptides.
The -glutamyl carboxylase gene is conserved between mammals (including
humans), insects, and molluscs. In fact, the correspondence of intron/exon
boundaries is surprisingly homologous and eight of the introns appear
to have predated the split in coelomate lineages in the Precambrian. (Bandyopadhyay,
Tissue Factor (TF) serves as a cell membrane attachment (tether) for one
of the protease enzymes of the clotting cascade (clotting factor VII).
It is homologous to cytokine receptors -receptors for erythropoeitin,
interleukins, colony stimulating factor, interferon, and several hormones.
This group belongs to the immunoglobulin superfamily which is one of the
largest protein families in the animal kingdom. Before vertebrates evolved
a coagulation cascade involving TF, receptors-related to TF were already
present on cell membranes and their functions included the response to
infection (such as might occur after a wound) (Bazan, 1990).