Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''CRYM''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. Multiple alternatively spliced transcript variants have been found for this gene.

Function

Crystallin In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast c ...

s 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

ornithine cyclodeaminase The enzyme ornithine cyclodeaminase (EC 4.3.1.12) catalyzes the chemical reaction L-ornithine \rightleftharpoons L-proline + NH4+ This enzyme belongs to the family of lyases, specifically ammonia lyases, which cleave carbon-nitrogen bonds. Th ...

s. The encoded protein does not perform a structural role in lens tissue, and instead it binds 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

NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...

or NADPH can be used as cofactor. The most active substrate at pH 5.0 is aminoethylcysteine ketimine (AECK), however at neutral pH (pH 7.2) the most active substrate is 1-piperideine-2-carboxylate which is an important part of the

pipecolic acid Pipecolic acid (piperidine-2-carboxylic acid) is an organic compound with the formula HNC5H9CO2H. It is a carboxylic acid derivative of piperidine and, as such, an amino acid, although not one encoded genetically. Like many other α-amino acids, p ...

pathway. The active form of

thyroxine File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

, 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

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

through thyroid hormone binding effects on the fibrocytes of the

cochlea The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory or ...

. 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 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.

Function

References

External links

Further reading