Nh. Kulkarni et al., Characterization and differential expression of a human gene family of olfactomedin-related proteins, GENET RES, 76(1), 2000, pp. 41-50
Olfactomedin-related proteins are secreted glycoproteins with conserved C-t
erminal motifs. Olfactomedin was originally identified as the major compone
nt of the mucus layer that surrounds the chemosensory dendrites of olfactor
y neurons. Homologues were subsequently found also in other tissues, includ
ing the brain and in species ranging from Caenorhabditis elegans to Homo sa
piens. Most importantly, the TIGR/myocilin protein, expressed in the eye an
d associated with the pathogenesis of glaucoma, is an olfactomedin-related
protein. The prevalence of olfactomedin-related proteins among species and
their identification in different tissues prompted us to investigate whethe
r a gene family exists within a species, specifically Homo sapiens. A GenBa
nk search indeed revealed an entire human gene family of olfactomedin-relat
ed proteins with at least five members, designated hOlfA through hOlfD and
the TIGR/myocilin protein. hOlfA corresponds to the rat neuronal AMZ protei
n. Phylogenetic analyses of 18 olfactomedin-related sequences resolved four
distinct subfamilies. Among the human proteins, hOlfA and hOlfC, both expr
essed in brain, are most closely related. Northern blot analyses of 16 huma
n tissues demonstrated highly specific expression patterns: hOlfA is expres
sed in brain, hOlfB in pancreas and prostate, hOlfC in cerebellum, hOlfD in
colon, small intestine and prostate and TIGR/myocilin in heart and skeleta
l muscle. The link between TIGR/myocilin and ocular hypertension and the ex
pression of several of these proteins in mucus-lined tissues suggest that t
hey play an important role in regulating physical properties of the extrace
llular environment. Future studies can now assess whether other members of
this gene family, like TIGR/myocilin, are also associated with human diseas
e processes.