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 2018_02

Published February 28, 2018

Headline

Escaping friendly fire

During the first hours of an infection, our safety relies almost entirely on the innate immune system, and predominantly on neutrophils. The encounter between neutrophils and invading microbes leads to neutrophil activation and to the engulfment of pathogens into intracellular phagosomes, where exposure to high concentrations of reactive oxygen species (ROS) and antimicrobial peptides eventually kill them. Neutrophils defend us not only in life but also in death, when they release chromatin and granule proteins that together form extracellular fibers, called ‘neutrophil extracellular traps’ or NETs, which catch and prevent the spread of microorganisms. NETs are covered with antimicrobial compounds, such as cathelicidin peptides, as well as histones, which can also effectively neutralize intruders. This process is so efficient that extracellular DNases able to catalyze NET disruption serve as virulence factors in several pathogenic bacteria, such as in group A Streptococcus.

NETs are a double-edged sword and have to be regulated very tightly. Indeed, free extracellular DNA is a potent trigger of autoimmune response, such as that encountered in systemic lupus erythematosus (SLE) that is characterized by circulating anti-DNA antibodies. NETs can also initiate vascular occlusion in a fibrin-independent manner. In other words, NETs are not an innocuous therapy in the middle/long term and the host has to get rid of them quickly. Timely removal of NET chromatin by DNases DNASE1 and DNASE1L3 has been shown to play a crucial role in the prevention of autoimmunity. However, it was not known until recently what mechanism was involved in NET clearance under inflammatory conditions. This issue was addressed by Jimenez-Alcazar and colleagues. They created knockout mice lacking both DNASE1 and DNASE1L3. Mutant animals were treated with granulocyte colony-stimulating factor (G-CSF) to induce chronic neutrophilia, a condition mimicking acute inflammation. While wild-type mice showed no sign of distress, all double knockout animals exhibited features of infection-induced thrombotic microangiopathies (TMAs) and died within 6 days. This phenotype could be reversed by the reintroduction of DNASE1 or DNASE1L3, but not by an anti-thrombotic treatment, further supporting the idea that NETs can clog vessels by themselves. TMAs are a well-known complication encountered by patients suffering from systemic bacterial infections. Analysis of lungs from patients with acute respiratory distress syndrome and/or sepsis revealed numerous NET-derived clots in their blood vessels. It is too early yet to propose DNase treatment for TMA patients, but at least it opens new therapeutic perspectives.

As of this release, murine DNASE1 and DNASE1L3 and their orthologs in other mammalian species have been updated and are now publicly available.

UniProtKB news

UniProtKB FASTA headers: Addition of NCBI taxonomy identifier

In order to avoid ambiguities and simplify parsing, we have added the NCBI taxonomy identifier to UniProtKB FASTA headers.

Previous format:

>db|UniqueIdentifier|EntryName ProteinName OS=OrganismName [GN=GeneName ]PE=ProteinExistence SV=SequenceVersion

New format:

>db|UniqueIdentifier|EntryName ProteinName OS=OrganismName OX=OrganismIdentifier [GN=GeneName ]PE=ProteinExistence SV=SequenceVersion

Where:

  • db is ‘sp’ for UniProtKB/Swiss-Prot and ‘tr’ for UniProtKB/TrEMBL.
  • UniqueIdentifier is the primary accession number of the UniProtKB entry.
  • EntryName is the entry name of the UniProtKB entry.
  • ProteinName is the recommended name of the UniProtKB entry as annotated in the RecName field. For UniProtKB/TrEMBL entries without a RecName field, the SubName field is used. In case of multiple SubNames, the first one is used. The ‘precursor’ attribute is excluded, ‘Fragment’ is included with the name if applicable.
  • OrganismName is the scientific name of the organism of the UniProtKB entry.
  • OrganismIdentifier is the unique identifier of the source organism, assigned by the NCBI.
  • GeneName is the first gene name of the UniProtKB entry. If there is no gene name, OrderedLocusName or ORFname, the GN field is not listed.
  • ProteinExistence is the numerical value describing the evidence for the existence of the protein.
  • SequenceVersion is the version number of the sequence.

Examples:

>sp|Q8I6R7|ACN2_ACAGO Acanthoscurrin-2 (Fragment) OS=Acanthoscurria gomesiana OX=115339 GN=acantho2 PE=1 SV=1
>sp|P27748|ACOX_CUPNH Acetoin catabolism protein X OS=Cupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337) OX=381666 GN=acoX PE=4 SV=2
>sp|P04224|HA22_MOUSE H-2 class II histocompatibility antigen, E-K alpha chain OS=Mus musculus OX=10090 PE=1 SV=1

>tr|Q3SA23|Q3SA23_9HIV1 Protein Nef (Fragment) OS=Human immunodeficiency virus 1  OX=11676 GN=nef PE=3 SV=1
>tr|Q8N2H2|Q8N2H2_HUMAN cDNA FLJ90785 fis, clone THYRO1001457, moderately similar to H.sapiens protein kinase C mu OS=Homo sapiens OX=9606 PE=2 SV=1

The same modification has been applied to FASTA headers of alternative isoforms in UniProtKB/Swiss-Prot), where the new format is:

>sp|IsoID|EntryName Isoform IsoformName of ProteinName OS=OrganismName OX=OrganismIdentifier[ GN=GeneName]

Example:

>sp|Q4R572-2|1433B_MACFA Isoform Short of 14-3-3 protein beta/alpha OS=Macaca fascicularis OX=9541 GN=YWHAB

Cross-references to CarbonylDB

Cross-references have been added to the CarbonylDB database, a resource of protein carbonylation sites.

CarbonylDB is available at http://digbio.missouri.edu/CarbonylDB/.

The format of the explicit links is:

Resource abbreviationCarbonylDB
Resource identifierUniProtKB accession number

Example: P02768

Show all entries having a cross-reference to CarbonylDB.

Text format

Example: P02768

DR   CarbonylDB; P02768; -.

XML format

Example: P02768

<dbReference type="CarbonylDB" id="P02768"/>

RDF format

Example: P02768

uniprot:P02768
  rdfs:seeAlso <http://purl.uniprot.org/carbonyldb/P02768> .
<http://purl.uniprot.org/carbonyldb/P02768>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/CarbonylDB> .

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):

  • O-AMP-serine

RDF news

Change of URIs for OrthoDB

For historic reasons, UniProt had to generate URIs to cross-reference databases that did not have an RDF representation. Our policy is to replace these by the URIs generated by the cross-referenced database once it starts to distribute an RDF representation of its data.

The URIs for the OrthoDB database have therefore been updated from:

http://purl.uniprot.org/orthodb/<ID>

to:

http://purl.orthodb.org/odbgroup/<ID>

If required for backward compatibility, you can use the following query to add the old URIs:

PREFIX owl:<http://www.w3.org/2002/07/owl#>
PREFIX up:<http://purl.uniprot.org/core/>
INSERT
{
   ?protein rdfs:seeAlso ?old .
   ?old owl:sameAs ?new .
   ?old up:database <http://purl.uniprot.org/database/orthodb> .
}
WHERE
{
   ?protein rdfs:seeAlso ?new .
   ?new up:database <http://purl.uniprot.org/database/OrthoDB> .
   BIND(iri(concat('http://purl.uniprot.org/orthodb/', substr(str(?new),31))) AS ?old)
}

The dereferencing of existing http://purl.uniprot.org/orthodb/<ID> URIs will be maintained.

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again