Oncomodulin

Oncomodulin is a parvalbumin-family calcium-binding protein expressed and secreted by macrophages (that typically traffic to tissue as an inflammatory response or after injury).

Oncomodulin is present in the eye. It is small, acidic, has a high calcium-binding activity, and consists of 108 amino acid residues. It is released by macrophages in the vitreous and the retina to promote nerve regeneration in the eye. This regeneration can be done in response to inflammation in the eye and promote regrowth in the eye to repair retinal injury. The regeneration effects of oncomodulin outcompetes other neurotrophic factors like BDNF, CNTF, and GDNF. When added to retinal nerve cells in a petri dish with no other growth factors present, oncomodulin has been shown to promote neuron regrowth at 5-7 times the normal rate.

Oncomodulin has been found in cytotrophoblasts of human and rat placenta and in the early stages of embryos. In vivo, oncomodulin promotes regeneration of the optic nerve in rats. It has also been found in different types of human and rodent tumors. However, it has never been found in healthy human or rat tissues.

To date, it has been found in the central nervous system in inner ear hair cells and retinal ganglion cells. Oncomodulin promotes axon regeneration in retinal ganglion cells and maintains functioning in mouse cochlear hair cells.

Oncomodulin is highly conserved across vertebrate evolution (NCBI database). It is a smaller calcium-binding protein (11.7-kDa) which resembles the EF-hand domain of calmodulin (32% sequence identity), alpha-parvalbumin (54%), S100-beta (34%), and calbindin (25%) and resembles alpha-parvalbumin in its N-terminal region (52%). It has a 40-residue N-terminal domain with an inactive calcium binding site and a 70-residue EF-hand domain with one low affinity Ca²⁺ and Mg²⁺ binding site and one high-affinity Ca²⁺ site.

Oncomodulin has a crystal structure and is a 12,000 Mr protein. Two Ca²⁺ atoms in oncomodulin are co-ordinated with seven oxygen atoms and one water molecule. The third Ca²⁺ atom is co-ordinated with five oxygen atoms and two water molecules. Both of the Ca²⁺ molecules are bound to the CD and EF loops. The distances between Ca and O in the molecular structure range from 2.07 A to 2.64 A, which indicates that the molecule is tightly bound together. The backbone structure of oncomodulin closely resembles parvalbumin. It has a 50% amino acid identity to parvalbumin and a very similar structure.

The oncomodulins, sometimes called "beta-1 parvalbumins," are an ancient family of parvalbumins that can be found at conserved genome locations in species as different as cartilaginous fish, bony fish, and mammals.

For oncomodulin to work properly, it must have elevated levels of cAMP and the sugar mannose, which is present in the vitreous of the eye. cAMP increases the effectiveness of oncomodulin several times more than just having oncomodulin and cAMP alone. Oncomodulin is activated by activating downstream signaling of Ca²⁺, calmodulin kinase, and gene transcription.