A set of orthologous plasma proteins found in human, sheep, pig, cow and ro
dents, now collectively designated fetuin-A, constitutes the fetuin family.
Fetuin-A has been identified as a major protein during fetal life and is a
lso involved in important functions such as inhibition of the insulin recep
tor tyrosine kinase activity, protease inhibitory activities and developmen
t-associated regulation of calcium metabolism and osteogenesis. Furthermore
, fetuin-A is a key partner in the recovery phase of an acute inflammatory
response. We now describe a second protein of the fetuin family, called fet
uin-B, which is found at least in human and rodents. On grounds of domain h
omology, overall conservation of cysteine residues and chromosomal assignme
nts of the corresponding genes in these species, fetuin-B is unambiguously
a paralogue of fetuin-A. Yet, fetuin-A and fetuin-B exhibit significant dif
ferences at the amino acid sequence level, notably including variations wit
h respect to the archetypal fetuin-specific signature. Differences and simi
larities in terms of gene regulation were also observed. Indeed, studies pe
rformed during development in rat and mouse showed for the first time high
expression of a member of the fetuin family in adulthood, as shown with the
fetuin-B mRNA in rat. However, like its fetuin-A counterpart, the fetuin-B
mRNA level is down-regulated during the acute phase of experimentally indu
ced inflammation in rat.