Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light.

The name cryptochrome was proposed as a portmanteau combining the chromatic nature of the photoreceptor, and the cryptogamic organisms on which many blue-light studies were carried out.

Employing transfection, initial studies on yeast have capitalized on the potential of CRY2 heterodimerization to control cellular processes, including gene expression, by light.

However, by 1995 it became clear that the products of the HY4 gene and its two human homologs did not exhibit photolyase activity and were instead a new class of blue light photoreceptor hypothesized to be circadian photopigments.

[11][12] Cryptochromes (CRY1, CRY2) are evolutionarily old and highly conserved proteins that belong to the flavoproteins superfamily that exists in all kingdoms of life.

Cryptochromes are derived from and closely related to photolyases, which are bacterial enzymes that are activated by light and involved in the repair of UV-induced DNA damage.

Studies of Drosophila cry-knockout mutants led to the later discovery that cryptochrome proteins are also involved in regulating the mammalian circadian clock.

[13] Cry mutants (cryb) were found to express arrhythmic levels of luciferase as well as PER and TIM proteins in photoreceptor cells.

[13] Despite the arrhythmicity of these protein levels, cryb mutants still showed rhythmicity in overall behavior but could not entrain to short pulses of light, leading researchers to conclude that the dorsal and ventral lateral neurons (the primary pacemaker cells of Drosophila) were still functioning effectively.

[13] It is therefore likely that plant and animal cryptochrome proteins show a unique case of convergent evolution by repeatedly evolving new functions independently of each other from a single common ancestral cry gene.

[15] The structure of cryptochrome involves a fold very similar to that of photolyase, arranged as an orthogonal bundle with a single molecule of FAD noncovalently bound to the protein.

[15] These proteins have variable lengths and surfaces on the C-terminal end, due to the changes in genome and appearance that result from the lack of DNA repair enzymes.

[15] The Ramachandran plot shows that the secondary structure of the CRY1 protein is primarily a right-handed alpha helix with little to no steric overlap.

Their flavin chromophore is reduced by light and transported into the cell nucleus, where it affects the turgor pressure and causes subsequent stem elongation.

CRY interacts with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and PIF5, repressors of photomorphogenesis and promoter of hypocotyl elongation, to repress PIF4 and PIF5 transcription activity.

Researchers have also recently proposed a model in which FAD− is excited to its doublet or quartet state by absorption of a photon, which then leads to a conformational change in the CRY protein.

In contrast, the eyes of most animals use photo-sensitive opsins expressed in photoreceptor cells, which communicate information about light from the environment to the nervous system.

Therefore, the sponge's unique eyes must have evolved a different mechanism to detect light and mediate phototaxis, possibly with cryptochromes or other proteins.

[31] Research by Margiotta and Howard (2020) shows that the PMTR of the chicken iris striated muscle occurs with CRY gene activation by 430 nm blue light.

[30] Studies in animals and plants suggest that cryptochromes play a pivotal role in the generation and maintenance of circadian rhythms.

[39] In addition, mice lacking Cry1 or Cry2 genes exhibit differentially altered free running periods, but are still capable of photoentrainment.

These results suggest that cryptochromes play a photoreceptive role, as well as acting as negative regulators of Per gene expression in mice.

Exposure to blue light induces a conformation similar to that of the always-active CRY mutant with a C-terminal deletion (CRYΔ).

[28] The half-life of this conformation is 15 minutes in the dark and facilitates the binding of CRY to other clock gene products, PER and TIM, in a light-dependent manner.

According to a 2021 study, metabolic outputs, measured by bowel movements, were severely different for participants who were wild type in comparison to those with the CRY1Δ11 variant.

Experimental data suggests that cryptochromes in the photoreceptor neurons of birds' eyes are involved in magnetic orientation during migration.

[57] Nevertheless, these results have later turned out to be irreproducible under strictly controlled conditions in another laboratory,[58] suggesting that plant cryptochromes do not respond to magnetic fields.

[61] Magnetoreception is hypothesized to function through the surrounding magnetic field's effect on the correlation (parallel or anti-parallel) of these radicals, which affects the lifetime of the activated form of cryptochrome.

Activation of cryptochrome may affect the light-sensitivity of retinal neurons, with the overall result that the animal can sense the magnetic field.

[63][64] The absence of spin-selective recombination of these radical pairs on the nanosecond to microsecond timescales seems to be incompatible with the suggestion that magnetoreception by cryptochromes is based on the forward light reaction.