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 2020_04

Published August 12, 2020

Headline

Inflammation: the Good, the Bad and the Ugly

In a world filled with (microbial) foes, inflammation is our best friend, helping us fight against invading microorganisms, promoting wound healing and tissue regeneration. When it gets out of hand, however, it becomes our worst enemy. For instance, inflammation is required for mice to fight Influenza virus A (IAV) infections, but animals challenged with high doses of virus experience elevated levels of inflammation, destruction of airway epithelia and eventually die, unless they are deficient in MLKL protein, an endogenous protein that induces cell death in response to orthomyxovirus infection.

The mechanism leading to this fatal issue has been recently elucidated. When IAV infects cells and replicates, newly formed IAV RNA duplexes can adopt the Z-confirmation. These very peculiar RNAs are recognized by ZBP1 protein as a pathogen-associated molecular pattern (PAMP) and initiate a cascade of reactions. Activated ZBP1 recruits RIPK3, which in turn can induce one of two forms of programmed cell death, apoptosis and pro-inflammatory necroptosis. In the presence of RIPK1, apoptosis is favored. In the absence of RIPK1, RIPK3 phosphorylates MLKL, which then induces necroptosis. Programmed cell death is an effective mechanism of IAV clearance that not only eliminates infected cells to limit virus spread but also serves to catalyze adaptive immune responses. When cell death is unrestrained, or when the mode of cell death is primarily necrotic, then injury and severe illness ensue, despite virus clearance.

The dark side of inflammation also includes chronic inflammatory diseases and although progress has been made in this field, the causes that initiate pathogenic inflammatory responses still remain elusive. Could ZBP1 be a player in this deadly game? In other words, can ZBP1 be activated in the absence of any viral infections? An answer to these questions came from a recent publication by Jiao et al.. The authors showed that endogenous retroelements (EREs) produce double-stranded RNAs (dsRNAs) adopting a Z-confirmation. These dsRNAs are recognized by ZBP1 and activate it. EREs derive either from ancient retroviral infections or from active retrotransposons and constitute over half of the human and mouse genomes. Most dsRNAs identified by Jiao et al. originate from B2 and Alu short interspersed nuclear elements, followed by long interspersed nuclear elements (specifically, L1 elements) and long terminal repeat elements. Hence, these old mates of ours may still be able to mimic viral infections. Indeed in RIPK1 knockout mice, deregulation of ERE expression may trigger ZBP1-dependent skin inflammation. This mechanism may be relevant for the pathogenesis of inflammatory pathologies in humans, particularly in patients with variations in proteins that inhibit the ZBP1-MLKL-induced necroptotic pathway, such as RIPK1.

As of this release, ZBP1, RIPK3, and MLKL have been updated and are available in UniProtKB/Swiss-Prot.

UniProtKB news

Cross-references to GlyGen

Cross-references have been added to the GlyGen Computational and Informatics Resource for Glycoscience. GlyGen retrieves information from multiple international data sources, integrates and harmonizes this data and makes it searchable.

GlyGen is available at https://www.glygen.org.

The format of the explicit links is:

Resource abbreviationGlyGen
Resource identifierUniProtKB accession number
Optional information 1Glycosylation details

Example: P07766

Show all entries having a cross-reference to GlyGen.

Text format

Example: P14210

DR   GlyGen; P14210; 5 sites, 8 N-linked glycans (4 sites), 1 O-linked glycan (1 site).

XML format

Example: P14210

<dbReference type="GlyGen" id="P14210">
  <property type="glycosylation" value="5 sites, 8 N-linked glycans (4 sites), 1 O-linked glycan (1 site)"/>
</dbReference>

RDF format

Example: P14210

uniprot:P07766
  rdfs:seeAlso <http://purl.uniprot.org/glygen/P14210> .
<http://purl.uniprot.org/glygen/P14210>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/GlyGen> ;
  rdfs:comment "5 sites, 8 N-linked glycans (4 sites), 1 O-linked glycan (1 site)" .

Cross-references to PathwayCommons

Cross-references have been added to the PathwayCommons, a resource that aims to collect and disseminate biological pathway and interaction data. Data is collected from partner databases and is represented in the BioPAX standard. By representing data in BioPAX, Pathway Commons is able to provide a detailed representation of a variety of biological concepts including: Biochemical reactions; gene regulatory networks; and genetic interactions; transport and catalysis events; and physical interactions involving proteins, DNA, RNA and small molecules and complexes.

PathwayCommons is available at http://www.pathwaycommons.org.

The format of the explicit links is:

Resource abbreviationPathwayCommons
Resource identifierUniProtKB accession number

Example: P01042

Show all entries having a cross-reference to PathwayCommons.

Text format

Example: P01042

DR   PathwayCommons; P01042; -.

XML format

Example: P01042

<dbReference type="PathwayCommons" id="P01042"/>

RDF format

Example: P01042

uniprot:P01042
  rdfs:seeAlso <http://purl.uniprot.org/pathwaycommons/P01042> .
<http://purl.uniprot.org/pathwaycommons/P01042>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/PathwayCommons> .

Change to the cross-references to GlyConnect

We have introduced an additional field in the cross-references to the GlyConnect protein glycosylation database, a platform integrating sources of information to help characterize the molecular components of protein glycosylation. This allows us to provide some additional information, e.g. about the nature of the glycans and the number of glycosylation sites.

The format of the explicit links is:

Resource abbreviationGlyConnect
Resource identifierResource identifier
Optional information 1Glycosylation details

Text format

Example: P12763

Previous format:

DR   GlyConnect; 22; -.

New format:

DR   GlyConnect; 22; 49 N-Linked glycans (3 sites), 13 O-Linked glycans (6 sites).

XML format

Example: P12763

Previous format:

<dbReference type="GlyConnect" id="22"/>

New format:

<dbReference type="GlyConnect" id="22">
  <property type="glycosylation" value="49 N-Linked glycans (3 sites), 13 O-Linked glycans (6 sites)"/>
</dbReference>

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

RDF format

Example: P12763

Previous format

uniprot:P12763
  rdfs:seeAlso <http://purl.uniprot.org/glyconnect/22> .
<http://purl.uniprot.org/glyconnect/22>
  rdf:type <http://purl.uniprot.org/core/Resource> ;
  <http://purl.uniprot.org/core/database> <http://purl.uniprot.org/database/GlyConnect> .

New format:

uniprot:P12763
  rdfs:seeAlso <http://purl.uniprot.org/glyconnect/22> .
<http://purl.uniprot.org/glyconnect/22>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/GlyConnect> ;
  rdfs:comment "49 N-Linked glycans (3 sites), 13 O-Linked glycans (6 sites)" .

New automatic annotation system ARBA (Association-Rule-Based Annotator)

In the UniProt Automatic Annotation pipeline which enhances unreviewed (UniProtKB/TrEMBL) records by enriching them with automatic classification and annotation, the SAAS (Statistical Automatic Annotation System) component has been superseded by the more powerful ARBA (Association-Rule-Based Annotator). ARBA is a multiclass learning system trained on expertly annotated entries in UniProtKB/Swiss-Prot. ARBA uses rule mining techniques to generate concise annotation models with the highest representativeness and coverage for annotation, based on the properties of InterPro group membership and taxonomy. ARBA employs a data exclusion set that censors data not suitable for computational annotation (such as specific biophysical or chemical properties) and generates human-readable rules for each release. ARBA rules can be browsed and searched via the website.

Changes to the controlled vocabulary of human diseases

New diseases:

Changes to the controlled vocabulary for PTMs

New term for the feature key 'Cross-link' ('CROSSLNK' in the flat file):

  • Isoaspartyl glycine isopeptide (Gly-Asp)

New terms for the feature key 'Modified residue' ('MOD_RES' in the flat file):

  • 2-oxo-5,5-dimethylhexanoate
  • 3-methylisoleucine
  • 3-methylvaline
  • 3-methyl-D-valine
  • N4-methyl-D-asparagine
  • 3-hydroxyvaline (Thr)
  • (3S)-3-methylglutamine
  • 3-hydroxy-D-valine
  • (3R)-N4-methyl-3-hydroxy-D-asparagine
  • 3,3-dimethylmethionine
  • Diphosphoserine
  • Diphosphothreonine

Modified terms for the feature key 'Modified residue' ('MOD_RES' in the flat file):

  • Lactic acid -> D-lactate
  • 3-hydroxyvaline -> 3-hydroxyvaline (Val)
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
单机德州扑克中文版 快3贵州 喜乐彩中奖号码 上海配资炒股 11选5玩法及中奖规则 广东十一选五一定牛 吉林11选5怎么玩怎么看 河北十一选五走势分布图 福建快3中二不同 股票融资比例最高多少 河南快三技巧规律 江苏快三玩法中奖规则 云南11选5追号 内蒙古快三计算办法 中国福利彩票3d彩吧 宁夏11选5平台注册 广西快乐双彩开奖彩控