Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a
protein that in humans is encoded by the ''CRYM''
gene. Multiple alternatively spliced transcript variants have been found for this gene.
Function
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
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
and has sequence similarity to bacterial
ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds
thyroid hormone
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 ...
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 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 pathway. The active form of
thyroxine, T
3, 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.
Disruption of the CRYM gene leads to decreased T
3 concentrations in both tissues and serum without alteration of peripheral T
3 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.
References
External links
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Further reading
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Thyroid
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