CRYM

Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a is_associated_with::protein that in humans is encoded by the CRYM is_associated_with::gene. Multiple alternatively spliced transcript variants have been found for this gene.

Function
is_associated_with::Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial is_associated_with::ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds is_associated_with::thyroid hormone for possible regulatory or developmental roles.

Its enzyme function has been determined as a ketimine reductase, reducing cyclic ketimines to their reduced forms. Either is_associated_with::NADH or NADPH can be used as cofactor however NADH is preferred. The most active substrate is aminoethylcysteine ketimine (AECK). The enzyme is also active in the is_associated_with::pipecolic acid pathway. The active form of is_associated_with::thyroxine, T3, has been found to be a potent inhibitor at nanomolar concentrations.

Besides its role in lens biology, CRYM seems also to be involved in thyroid hormone signalling in other tissues. It could be demonstrated that CRYM mutations may cause is_associated_with::deafness through thyroid hormone binding effects on the fibrocytes of the is_associated_with::cochlea. Disruption of the CRYM gene leads to decreased T3 concentrations in both tissues and serum without alteration of peripheral T3 action in vivo.

The existence of intracellular thyroid hormone binding proteins has been postulated from mathematical modelling of is_associated_with::pituitary-thyroid homeostasis. Binding properties have been assumed to be similar to those of extracellular binding proteins, however it is not clear, if THBP is the only intracellular thyroid hormone binding protein.