Olfactomedin-related proteins are secreted glycoproteins with conserved C-terminal motifs.
Olfactomedin was originally identified as the major component of the mucus layer that surrounds
the chemosensory dendrites of olfactory neurons. Homologues were subsequently found also in
other tissues, including the brain and in species ranging from Caenorhabditis elegans to Homo
sapiens. Most importantly, the TIGR/myocilin protein, expressed in the eye and 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 whether a gene family exists within a species, specifically Homo sapiens. A GenBank
search indeed revealed an entire human gene family of olfactomedin-related proteins with at least
five members, designated hOlfA through hOlfD and the TIGR/myocilin protein. hOlfA
corresponds to the rat neuronal AMZ protein. Phylogenetic analyses of 18 olfactomedin-related
sequences resolved four distinct subfamilies. Among the human proteins, hOlfA and hOlfC, both
expressed in brain, are most closely related. Northern blot analyses of 16 human tissues
demonstrated highly specific expression patterns: hOlfA is expressed in brain, hOlfB in pancreas
and prostate, hOlfC in cerebellum, hOlfD in colon, small intestine and prostate and
TIGR/myocilin in heart and skeletal muscle. The link between TIGR/myocilin and ocular
hypertension and the expression of several of these proteins in mucus-lined tissues suggest that
they play an important role in regulating physical properties of the extracellular environment.
Future studies can now assess whether other members of this gene family, like TIGR/myocilin, are
also associated with human disease processes.