Nocturnin is a human

hydrolase Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...

enzyme that is involved in metabolism and its expression is controlled by the rhythmic circadian clock. It is encoded by the NOCT gene located on chromosome 4. Nocturnin contains a c-terminal structural domain of the Endonuclease/Exonuclease/phosphatase family. A study in January 2019, demonstrated that

NADP+ 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 NADPH are the direct targets of Nocturnin. * The ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...

of Nocturnin is Curled. Knockouts of Curled lead to the curled wing

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

in fruit flies. The curled wing phenotype was first discovered by

Thomas Hunt Morgan Thomas Hunt Morgan (September 25, 1866 – December 4, 1945) was an American evolutionary biologist, geneticist, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role that ...

in 1915. In mice the Nocturnin ortholog is responsible for controlling diet and weight-gain, knockout mice do not gain weight when placed on a high-fat diet, when compared to normal mice containing Nocturnin. In mice it has also been shown that Nocturnin is rhythmically expressed even when mice are placed in complete darkness, demonstrating that Nocturnin expression is driven by our body's internal clock.

Cellular localization

Nocturnin was shown to have a

Mitochondrial targeting sequence A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

, which is located on the n-terminus of the protein. The targeting sequence of Nocturnin is cleaved off at the mitochondria to allow entry.

Enzymatic activity

Nocturnin was previously thought to deadenylate mRNAs of metabolic genes, but two studies in 2018 found that Nocturnin does not directly possess

ribonuclease Ribonuclease (commonly abbreviated RNase) is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within ...

activity. A study in January 2019 demonstrated that human Nocturnin is a phosphatase that acts directly on NADP(H) to remove the 2' phosphate. Curled, the Drosophila ortholog, was also shown to be an NADP(H) 2' phosphatase, which indicates that the enzymatic activity is conserved from humans to fruit flies.

Structure

Nocturnin contains a c-terminal structural domain of the Endonuclease/Exonuclease/phosphatase family (EEP). Its protein fold is similar to that of DNase I,

AP endonuclease Apurinic/apyrimidinic (AP) endonuclease is an enzyme that is involved in the DNA base excision repair pathway (BER). Its main role in the repair of damaged or mismatched nucleotides in DNA is to create a nick in the phosphodiester backbone of t ...

, INPP5B,

Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase (EC 3.1.4.12, also known as neutral sphingomyelinase, sphingomyelinase, or SMase; systematic name sphingomyelin cholinephosphohydrolase) is a hydrolase enzyme that is involved in sphingolipid metabolism reactions. ...

, TDP2, PDE12, and CNOT6L. As in the other EEP members, five conserved catalytic residues help coordinate a Magnesium atom, for Nocturnin the divalent metal participates in the NADP(H) phosphatase activity. The first structures of human Nocturnin were solved in 2017-2018
6BT1
6BT2
an
6MAL
ref name="Estrella 2018"/>). All three were of the c-terminal EEP-like domain of Nocturnin bound to its cofactor magnesium. In December 2018, the first structure of Nocturnin bound to its natural substrate, NADPH, was determined
6NF0

References

External links

* {{PDBe-KB2, Q9UK39, Nocturnin Enzymes of known structure Genes on human chromosome 4