CRYM
Encyclopedia
Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the CRYM gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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

Function

Crystallin
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 cancer tumors....

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
Nicotinamide adenine dinucleotide phosphate
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or TPN in older notation , is a coenzyme used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent....

 and has sequence similarity to bacterial ornithine cyclodeaminase
Ornithine cyclodeaminase
In enzymology, an ornithine cyclodeaminase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, L-ornithine, and two products, L-proline and NH3....

s. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...

 for possible regulatory or developmental roles.

Its enzyme function has been determined as a ketimine reductase
Thiomorpholine-carboxylate dehydrogenase
In enzymology, a thiomorpholine-carboxylate dehydrogenase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are thiomorpholine 3-carboxylate, NAD+, and NADP+, whereas its 4 products are 3,4-dehydro-thiomorpholine-3-carboxylate, NADH, NADPH, and H+.This enzyme belongs...

, reducing cyclic ketimines to their reduced forms. Either 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 pipecolic acid
Pipecolic acid
Pipecolic acid is a small organic molecule which accumulates in pipecolic acidemia. It is the carboxylic acid of piperidine.It can be associated with some forms of epilepsy....

 pathway. The active form of thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

, 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 through thyroid hormone binding effects on the fibrocytes of the cochlea
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....

. 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.
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