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UniProt release 2020_03

Published June 17, 2020

Headline

Mitochondrial call for help

Life is a continuous chain of issues that have to be addressed for survival and our cells know all about that. Hypoxia, amino acid deprivation, glucose deprivation, viral infection, endoplasmic reticulum stress are but a few examples. That's why eukaryotic cells have developed an elaborate signaling pathway, called the integrated stress response (ISR), which is activated in the cytosol in response to a range of physiological changes and pathological conditions. Stress stimuli that activate ISR all converge on the phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (EIF2A). Depending upon the stress stimulus, the reaction is catalyzed by one of the four following kinases: GCN2/EIF2AK4, PERK/EIF2AK3, PKR/EIF2AK2 and HRI/EIF2AK1. EIF2A phosphorylation leads to attenuation in 5' cap-dependent protein synthesis, while promoting the translation of selected mRNAs that harbor a short upstream open reading frame in their 5'-untranslated region, including those for transcription factors ATF4, ATF5 or DDIT3 (also known as CHOP). ISR is primarily a survival program, but exposure to severe stress can also lead to apoptosis.

Mitochondrial stress also strongly induces the expression of ATF4 and DDIT3, and hence triggers ISR, but the pathway signaling mitochondrial stress to the cytosol was elusive until the publication of two articles in March of this year. DDIT3 induction requires at least two mitochondrial proteins: OMA1 and DELE1, and the cytosolic kinase HRI. OMA1 is a metalloprotease located in the mitochondrial inner membrane. It is activated by mitochondrial dysfunction, possibly via membrane depolarization. OMA1 cleaves DELE1 in the intermembrane space and the N-terminally truncated DELE1 fragment enters the cytosol where it interacts with and activates HRI and hence stress response. The consequences of ISR during mitochondrial dysfunction are not yet fully understood and DELE1 may not be the only mitochondrial ISR activator, but one missing link between mitochondrial stress and ISR has been clearly established.

As of this release, the OMA1 protease and DELE1 have been updated and are available in UniProtKB/Swiss-Prot. To annotate DELE1, we took advantage of the new format announced last December, which allows us to describe product-specific features, be it that of an alternative splicing isoform, for example, or of a peptide resulting from proteolytic cleavage. EIF2AK1 activation is a function restricted to the DELE1 cleavage product, and this uniqueness is clearly reported in the 'FUNCTION' subsection dedicated to DELE1 short form.

UniProtKB news

Cross-references to IDEAL

Cross-references have been added to the IDEAL database, a database of Intrinsically Disordered proteins.

IDEAL is available at http://idp1.force.cs.is.nagoya-u.ac.jp/IDEAL/.

The format of the explicit links is:

Resource abbreviationIDEAL
Resource identifierResource identifier

Example: O15162

Show all entries having a cross-reference to IDEAL.

Text format

Example: O15162

DR   IDEAL; IID00006; -.

XML format

Example: O15162

<dbReference type="IDEAL" id="IID00006"/>

RDF format

Example: O15162

uniprot:O15162
  rdfs:seeAlso <http://identifiers.org/ideal/IID00006> .
<http://identifiers.org/ideal/IID00006>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/IDEAL> .

Cross-references to BioGRID-ORCS

Cross-references have been added to the BioGRID-ORCS database, a database of CRISPR phenotype screens.

BioGRID-ORCS is available at https://orcs.thebiogrid.org.

The format of the explicit links is:

Resource abbreviationBioGRID-ORCS
Resource identifierResource identifier
Optional information 1Number of hits

Example: Q96A29

Show all entries having a cross-reference to BioGRID-ORCS.

Text format

Example: Q96A29

DR   BioGRID-ORCS; 55343; 19 Hits in 787 CRISPR Screens.

XML format

Example: Q96A29

<dbReference type="BioGRID-ORCS" id="55343">
  <property type="hits" value="19 Hits in 787 CRISPR Screens"/>
</dbReference>

RDF format

Example: Q96A29

uniprot:Q96A29
  rdfs:seeAlso <http://purl.uniprot.org/biogrid-orcs/55343> .
<http://purl.uniprot.org/biogrid-orcs/55343>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/BioGRID-ORCS> ;
  rdfs:comment "19 Hits in 787 CRISPR Screens" .

Change to the cross-references to ABCD

We have introduced an additional field in the cross-references to the ABCD (AntiBodies Chemically Defined) database, a manually curated depository of sequenced antibodies. This allows us to specify the number of sequenced antibodies available for a given protein in UniProtKB.

Text format

Example: O75084

Previous format:

DR   ABCD; O75084; -.

New format:

DR   ABCD; O75084; 10 sequenced antibodies.

XML format

Example: O75084

Previous format:

<dbReference type="ABCD" id="O75084"/>

New format:

<dbReference type="ABCD" id="O75084"/>
  <property type="antibodies" value="10 sequenced antibodies"/>
</dbReference>

This change does not affect the XSD, but may nevertheless require code changes.

RDF format

Example: O75084

Previous format:

uniprot:O75084
  rdfs:seeAlso <http://purl.uniprot.org/abcd/O75084> .
<http://purl.uniprot.org/abcd/O75084>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/ABCD> .

New format:

uniprot:O75084
  rdfs:seeAlso <http://purl.uniprot.org/abcd/O75084> .
<http://purl.uniprot.org/abcd/O75084>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/ABCD> ;
  rdfs:comment "10 sequenced antibodies" .

Change of the cross-references to MycoCLAP

The MycoCLAP resource has changed its name to CLAE and we have updated our cross-references to reflect this name change.

Cross-references to BioGRID

The BioGrid database was renamed BioGRID. We changed the database name in the relevant cross-references (DR lines in the flat file) accordingly.

Example:

DR   BioGRID; 198188; 12.

Cross-references to Unimod in the ptmlist.txt document file

The ptmlist.txt document, which is available by FTP and on the website, describes post-translational modifications (PTMs) annotated in the UniProt knowledgebase. This release sees the addition of optional cross-references from ptmlist.txt to Unimod, an open access database of protein modifications for use in mass spectrometry applications which provides molecular-level details of PTMs (both natural and non-natural) including molecular formula, target residues, monoisotopic and average mass shifts and literature references with a community-driven curation.

Example:

ID   (3R)-3-hydroxyasparagine
AC   PTM-0369
FT   MOD_RES
..
KW   Hydroxylation.
..
DR   Unimod; 35.

This new mapping to Unimod will facilitate the integration of data on PTMs identified by mass spectrometry based proteomics.

We have currently mapped 236 of the most common PTMs in UniProtKB to Unimod and will continue to add new cross-references to Unimod in forthcoming releases. This mapping of PTMs to Unimod is part of our ongoing work on the standardization of knowledge of PTMs in UniProtKB by providing cross-references to a resource which is widely used in proteomics bioinformatics. We welcome your feedback on these current and future developments.

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 'Lipidation' ('LIPID' in the flat file):

  • 3'-prenyl-2',N2-cyclotryptophan
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