PER3

Key takeaways

PER3 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect PER3 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of PER3 from memory before moving on to harder problems.

Reference excerpt

The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes. It is a circadian gene associated with delayed sleep phase syndrome in humans.

History The Per3 gene was independently cloned by two research groups (Kobe University School of Medicine and Harvard Medical School) who both published their discovery in June 1998. The mammalian Per3 was discovered by searching for homologous cDNA sequences to Per2. The amino acid sequence of the mouse PERIOD3 protein (mPER3) is between 37-56% similar to the other two PER proteins.

Function This gene is a member of the Period family of genes. It is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression in the SCN continues in constant darkness, and a shift in the light/dark cycle evokes a proportional shift of gene expression in the SCN. PER1 and PER2 are necessary for molecular timekeeping and light responsiveness in the master circadian clock in the SCN, but little data is shown on the concrete function for PER3. PER3 was found to be important for endogenous timekeeping in specific tissues and those tissue-specific changes in endogenous periods result in internal misalignment of circadian clocks in Per3 double knockout (-/-) mice. PER3 may have a stabilizing effect on PER1 and PER2, and this stabilizing effect may be reduced in the PER3-P415A/H417R polymorphism.

Role in chronobiology The RNA levels of mPer3 oscillate with a circadian rhythm in both the SCN and in the eyes, as well as in peripheral tissues, including the liver, skeletal muscle, and testis. Unlike Per1 and Per2, of which the mRNA is induced in response to light, Per3 mRNA in the SCN does not respond to light. This suggests that Per3 may be regulated differently than either Per1 or Per2. The mPER3 protein contains a PAS domain, similar to mPER1 and mPER2. Likely, mPER3 binds to other proteins using this domain. However, while PER1/2 have been shown to be important in the transcription-translation feedback loop involved in the intracellular circadian clock, the influence of PER3 in this loop has not yet been fully elucidated, given that mPER3 does not appear to be functionally redundant to mPER1 and mPER2. mPer3 may not be a member of the core clock loop at all.

Animal studies While the Per3 gene is a paralog to the PER1 and PER2 genes, studies in animals generally show that it does not contribute significantly to circadian rhythms. Functional Per3-/- animals experience only small changes in free-running period, and do not respond significantly differently to light pulses. Per1-/- and Per2-/- animals experience a significant change in free-running period; however, knocking out Per3 in addition to either Per1 or Per2 has little effect on free-running rhythms. Furthermore, Per1-/-Per2-/- mice are completely arrhythmic, indicating that these two genes have much more importance to the biological clock than Per3. Per3 knockout mice experience a slightly shortened period of locomotor activity (by 0.5 hr) and are less sensitive to light, in that they entrain more slowly to changes in the light-dark cycle. PER3 may be involved in the suppression of behavioral activity in response to light, although mPer3 expression is not necessary for circadian rhythms.

Clinical significance The PER3 "length" polymorphism in the 54-bp repeat sequence in exon 18 (GenBank accession no. AB047686) is a structural polymorphism due to an insertion or deletion of 18 amino acids in a region encoding a putative phosphorylation domain. The polymorphism has been associated with diurnal preference and delayed sleep phase syndrome. A longer allele polymorphism is associated with "morningness" and the short allele with "eveningness." The short allele is also associated with delayed sleep phase syndrome. The length polymorphism has also been shown to inhibit adipogenesis and Per3 knockout mice were shown to have increased adipose tissue and decreased muscle tissue compared to wild type. Additionally, the presence of the length polymorphism has also been shown to be associated with type 2 diabetes mellitus (T2DM) patients as compared to non-diabetic control patients. The PER3-P415A/H417R polymorphism has been linked to familial advanced sleep phase syndrome in humans, as well as to seasonal affective disorder, though when knocked in to mice, the polymorphism causes a delayed sleep phase.

Gene

Orthologs The following is a list of some orthologs of the PER3 gene in other species:

Paralogs PER1 PER2

Gene location The human PER3 gene is located on chromosome 1 at the following location:

Start: 7,784,320 bp Finish: 7,845,181 bp Length: 60,862 bases Exons: 25 PER3 has 19 transcripts (splice variants).

Protein structure The PER3 protein has been identified to have the following features:

Size: 1201 amino acids Molecular mass: 131888 Da Quaternary structure: Homodimer

Post translational modifications The following are some known post transcriptional modifications to the Per3 gene:

Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus. Ubiquitinated. Modification sites at PhosphoSitePlus Modification sites at neXtProt

References

External links PER3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Illustrations

Worked examples

Example 1 — a first encounter with PER3

Start with the simplest possible case. Write down what PER3 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to PER3 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about PER3 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of PER3

In research: PER3 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses PER3 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: PER3 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Circadian rhythm, Genes on human chromosome 1, PAS-domain-containing proteins, so understanding it makes those chapters shorter.
In everyday life: Look for PER3 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study PER3 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what PER3 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain PER3 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is PER3 in simple terms?

The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes.

Why does PER3 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study PER3?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on PER3.