PROSITE documentation PDOC51132

Olfactomedin-like domain profile

The olfactomedin-like or OLF domain is a module of ~260 residues present in metazoan secreted glycoproteins with a characteristic tissue-specific expression. The domain is named after bullfrog olfactomedin, an extracellular matrix protein of olfactory neuroepithelium, whereof it forms the C-terminal part. Other proteins of the olfactomedin family contain the OLF domain in the C-terminal part, while the N-terminus is more variable. Proteins of the latrophilin subfamily have an OLF domain in the N-terminal extracellular part, C-terminal to a SUEL-type lectin domain (see <PDOC50228>), and their C-terminal part contains domains of the G-protein coupled receptors family 2 (see <PDOC00559> and <PDOC50221>). Some OLF domain proteins are involved in the formation of the extracellular matrix, e.g. bullfrog olfactomedin, sea urchin amassin and C. elegans unc-122. In addition, OLF domain proteins can function in developmental processes, e.g. noelin and tiarin [1,2,3,4].

Secondary structure predictions show that the OLF domain contains several β-strands [2,3,4]. A disulfide bond between two conserved cysteines within the OLF domain of human myocilin is implicated in mutations associated with severe forms of primary open angle glaucoma [3].

Some proteins known to contain an olfactomedin-like domain:

• Rana catesbeiana olfactomedin, a major component of the extracellular mucus matrix of the olfactory neuroepithelium, which may influence the development of the chemosensory dendrites of olfactory neurons.
• Human myocilin or trabecular meshwork inducible glucocorticoid response (TIGR) protein, a secreted glycoprotein that is highly expressed in the retina. Mutations of the MYOC gene cause some forms of primary open-angle glaucoma, a prevalent cause of blindness, and these are mostly located in the OLF domain [1,3].
• Mammalian noelin or pancortin proteins, secreted glycoproteins that promote neurogenesis.
• Mammalian optimedin, which is expressed in the brain and retina like noelin. Optimedin interacts with myocilin by the OLF domain [1].
• Mammalian latrophilin proteins, which belong to the secretin family of G-protein coupled receptors. These receptors mediate the toxic action of α-latrotoxin, a neurotoxin present in black widow spider venom; the OLF domain is not required for this interaction.
• Xenopus laevis tiarin, a secreted protein involved in neuronal development.
• Purple sea urchin amassin, an intercellular adhesion protein involved in clotting of coelomocytes by forming large disulfide-bonded aggregates.
• Caenorhabditis elegans unc-122 protein, which acts in neuromuscular junctions and affects locomotory behavior.

The profile we developed covers the entire olfactomedin-like domain.