SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProt release 2014_07

Published July 9, 2014

Headline

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.

UniProtKB news

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 abbreviation CCDS
Resource identifier CCDS identifier

Example: O70554

Show all entries having a cross-reference to CCDS.

Text format

Examples:

O70554
DR   CCDS; CCDS38509.1; -.
P00750
DR   CCDS; CCDS6126.1; -. [P00750-1]
DR   CCDS; CCDS6127.1; -. [P00750-3]

XML format

Examples:

O70554
<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 abbreviation GeneReviews
Resource identifier GeneReviews identifier

Example: O00555

Show all entries having a cross-reference to GeneReviews.

Text format

Example: O00555

DR   GeneReviews; CACNA1A; -.

XML format

Example: O00555

<dbReference type="GeneReviews" id="CACNA1A"/>

Changes to the controlled vocabulary of human diseases

New diseases:

Modified diseases:

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

New keywords:

Modified keywords:

UniParc news

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, "protein_name" and "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).

Examples:

<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.

FTP site news

Every folder on our FTP server now contains a file called RELEASE.metalink that specifies the size and MD5 checksum of every file in that folder, e.g.
ftp://ftp.uniprot.org/pub/databases/uniprot/knowledgebase/RELEASE.metalink

Metalink is an extensible metadata file format that describes one or more computer files available for download. It facilitates file verification and recovery from data corruption and lists alternate download sources (mirror URIs).

Various command line download tools, e.g. cURL version 7.30 or higher and aria2, support metalink.

Example: The following command will download all files in the current_release/ folder and verify their MD5 checksums:

curl --metalink ftp://ftp.uniprot.org/pub/databases/uniprot/current_release/RELEASE.metalink

They will be downloaded from one of the alternative locations mentioned in the metalink file. If one FTP server goes down during a download, programs can automatically switch to another mirror location. Some programs can also download segments from several FTP locations at the same time, which can make downloads much faster.

Please note that UniProt can be downloaded from the consortium member FTP sites at three different geographical locations:

USA: ftp://ftp.uniprot.org/pub/databases/uniprot
UK: ftp://ftp.ebi.ac.uk/pub/databases/uniprot
Switzerland: ftp://ftp.expasy.org/databases/uniprot

This information can be found in our FAQ.