UniProt release 2014_07
Published July 9, 2014
Lark or owl? PER3 is the answer
Unless you are like Napoleon who never needed more than 4 hours of sleep at a stretch, being both an early bird and a night owl, you certainly have a diurnal preference. It is not a simple matter of taste, it is a matter of genetics, involving the PER3 gene.
In humans, the PER3 gene exists in 2 versions: a short one and a long one. The length variation depends upon the number of 18 amino-acid tandem repeats in the protein’s C-terminus: 4 in the short version, 5 in the long one. Roughly 10% of the population is homozygous for the long allele (PER3 5/5) and 50% for the short allele (PER3 4/4). This polymorphism correlates significantly with extreme diurnal preference, the longer allele being associated with morningness and the shorter allele with eveningness. In addition, PER3 5/5 individuals are more vulnerable to sleep deprivation than their PER3 4/4 counterparts, exhibiting greater cognitive performance impairment. When allowed to take naps, PER3 5/5 individuals show a greater ability to sleep independently of circadian phase, suggesting that the polymorphism modifies the sleep homeostatic response without influencing circadian parameters.
The molecular mechanism of this behavioral difference is not known and there was no animal model to investigate it until recently. Indeed, the 18 amino-acid polymorphism does not exist in non-primate mammals. Earlier this year, Hasan et al. published a study in which they created 2 knock-in mice. These mice contained a “humanized” PER3 exon 18 with either the 4-repeat or 5-repeat allele. The transgenic mice exhibited a phenotypic response to sleep deprivation and recovery consistent with the observations made in humans. 816 genes were differentially expressed in the cortex of Per3 4/4 and Per3 5/5 mice and a similar amount in the hypothalamus. At least some of these genes seem to be involved in the regulation of, or response to, sleep, as well as in neuronal development and function. For instance, some isoforms of the Homer1 gene, a marker of sleep homeostasis, were up-regulated in the Per3 5/5 compared to the Per3 4/4 hypothalamus.
With this tool in hand, we may be in a position to start identifying the genetic control of sleep architecture in humans and maybe unveil if Napoleon’s sleep ability was a true genetic oddity, the result of his iron will or just a historical myth.
As of this release, the human PER3 entry has been updated in UniProtKB/Swiss-Prot.
Cross-references to CCDS
Cross-references have been added to CCDS, the Consensus CDS project.
CCDS is available at http://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi.
The format of the explicit links is:
|Resource identifier||CCDS identifier|
DR CCDS; CCDS38509.1; -.P00750
DR CCDS; CCDS6126.1; -. [P00750-1] DR CCDS; CCDS6127.1; -. [P00750-3]
<dbReference type="CCDS" id="CCDS38509.1"/>P00750
<dbReference type="CCDS" id="CCDS6126.1"> <molecule id="P00750-1"/> </dbReference> <dbReference type="CCDS" id="CCDS6127.1"> <molecule id="P00750-3"/> </dbReference>
Cross-references to GeneReviews
Cross-references have been added to GeneReviews, a resource of expert-authored, peer-reviewed disease descriptions.
GeneReviews is available at http://www.ncbi.nlm.nih.gov/books/NBK1116/.
The format of the explicit links is:
|Resource identifier||GeneReviews identifier|
DR GeneReviews; CACNA1A; -.
<dbReference type="GeneReviews" id="CACNA1A"/>
Changes to the controlled vocabulary of human diseases
- Alzheimer disease 19
- Auriculocondylar syndrome 3
- Boucher-Neuhauser syndrome
- Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation
- Foveal hypoplasia 2
- Hyperphosphatasia with mental retardation syndrome 4
- Immunodeficiency 20
- Mental retardation, autosomal dominant 23
- Mental retardation, autosomal recessive 27
- Myopathy with extrapyramidal signs
- Polyarteritis nodosa
- Question mark ears, isolated
- Retinitis pigmentosa 23
- Retinitis pigmentosa 68
- Retinitis pigmentosa 69
- Richieri-Costa-Pereira syndrome
- Schwannomatosis 2
- Spastic paraplegia 64, autosomal recessive
- Spastic paraplegia 63, autosomal recessive
- Spinocerebellar ataxia, autosomal recessive, 15
- Spondylometaphyseal dysplasia with cone-rod dystrophy
- Cerebellar ataxia and hypogonadotropic hypogonadism -> Gordon Holmes syndrome
- Foveal hypoplasia -> Foveal hypoplasia 1
- Retinopathy exudative with bone marrow failure -> Dyskeratosis congenita, autosomal dominant, 5
- Schwannomatosis -> Schwannomatosis 1
Changes to the controlled vocabulary for PTMs
New term for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):
- L-isoglutamyl histamine
Modified term for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):
- N6-crotonyl-L-lysine -> N6-crotonyllysine
Changes to keywords
- Bacterial host gene expression shutoff by virus
- Bacterial host transcription shutoff by virus
- Eukaryotic host gene expression shutoff by virus
- Viral host range expansion by genetic inversion
- Abi system evasion by virus -> Evasion of bacteria-mediated translation shutoff by virus
- Host transcription shutoff by virus -> Eukaryotic host transcription shutoff by virus
- Host translation shutoff by virus -> Eukaryotic host translation shutoff by virus
- Inhibition of host translation factors by virus -> Inhibition of eukaryotic host translation factors by virus
- Inhibition of host transcription initiation by virus -> Inhibition of eukaryotic host transcription initiation by virus
- Viral primary attachment to host cell -> Viral attachment to host adhesion receptor
UniParc cross-references with protein and gene names
The UniParc XML format uses
dbReference elements to represent cross-references to external database records that contain the same sequence as the UniParc record. Additional information about an external database record is provided with different types of
property child elements. We have introduced two new types,
"gene_name", to show the preferred protein and gene name of external database records that provide this information. In this release we have added names for cross-references to UniProtKB and RefSeq. For UniProtKB entries that have several protein or gene names, UniParc shows only the main one, which is the same name that is shown in the UniProtKB FASTA format. We will soon added names for cross-references to ENA, Ensembl, EnsemblGenomes and model organism databases (FlyBase, SGD, TAIR, WormBase).
<dbReference type="UniProtKB/Swiss-Prot" id="P05067" version_i="3" active="Y" version="3" created="1991-11-01" last="2014-02-19"> <property type="NCBI_GI" value="112927"/> <property type="NCBI_taxonomy_id" value="9606"/> <property type="protein_name" value="Amyloid beta A4 protein"/> <property type="gene_name" value="APP"/> </dbReference> ... <dbReference type="UniProtKB/Swiss-Prot protein isoforms" id="P05067-2" version_i="1" active="Y" created="2003-03-28" last="2014-02-19"> <property type="NCBI_taxonomy_id" value="9606"/> <property type="protein_name" value="Isoform APP305 of Amyloid beta A4 protein"/> <property type="gene_name" value="APP"/> </dbReference>
This change did not affect the UniParc XSD, but may nevertheless require code changes.
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