Olfactomedin-2 (OLFM2, OM2), also called OlfC or neuronal olfactomedin-related endoplasmic reticulum-localized-2 (Noelin-2) is a 50 kDa (predicted), secreted member of the olfactomedin/noelin family of proteins (1 - 3). Since Noelin-2 has also been used to designate an alternately spliced form of Noelin-1, Olfactomedin-2 is the less ambiguous name (4). Olfactomedin domain-containing proteins are often found in neural tissues (3). Human Olfactomedin-2 expressed sequence tags have mainly been found in the brain and eye, and RNA in the cerebellum (1, 2). In zebrafish, Olfactomedin-2 expression is developmentally regulated and, like Noelin-1, may play a role in neural crest cell differentiation (5). The human Olfactomedin-2 cDNA encodes a 20 amino acid (aa) signal sequence and a 454 mature protein that contains two coiled-coil regions (aa 58 - 85 and 136 - 193) and an Olfactomedin domain (aa 194 - 446). Mature human Olfactomedin-2 shares 98% aa identity with rat, bovine and equine, 97% with mouse and canine, 81% with Xenopus, and 77% with zebrafish Olfactomedin-2. No alternate splice variants have been reported for Olfactomedin-2 (1). Polymorphisms of human Olfactomedin-2, with or without additional polymorphisms in optineurin (OPTN), have been associated with a small fraction of high intraocular pressure or open-angle glaucoma cases in Japanese patients (6). The family member myocilin shows stronger association with these ocular disorders, and either myocilin or Noelin-1 might heterodimerize with Olfactomedin-2 (1). Evidence suggests that Olfactomedin-2 has evolved from Noelin-1 gene duplication, and myocilin from Olfactomedin-2 gene duplication (1).
