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UniProt release 2013_12

Published December 11, 2013

Headline

The aflatoxin biosynthetic pathway annotated in UniProtKB/Swiss-Prot

Aflatoxins are very important members of the family of mycotoxins, that contaminate food and feed crops. More than 14 different aflatoxins have been identified so far. These secondary metabolites are mainly produced by the filamentous fungi Aspergillus flavus and Aspergillus parasiticus. These organisms grow in warm and humid locations, such as those where crops (e.g. rice, maize and ground nuts) are stored.

Intake of aflatoxins has both acute and long term effects. Acute aflatoxin poisoning leads to effects such as hemorrhagic necrosis of the liver, bile duct proliferation, edema and lethargy. In addition, aflatoxins have immunosuppressive effects and interfere with nutrient uptake leading to malnutrition (kwashiorkor). The most toxic of the aflatoxins, aflatoxin B1, is the most potent naturally occurring carcinogen known. The carcinogenic effect of aflatoxins is mediated by 2 cytochromes P-450 enzymes, CYP1A2 and CYP3A4. CYP1A2 and CYP3A4 turn the aflatoxins into much more reactive epoxides that react with DNA bases and induce mutations, leading, in the long term, to liver cancer. Overall it is estimated that aflatoxins negatively impact up to 5 billion people who live in warm and humid climates. The presence of dietary aflatoxin is strongly associated with incidences of liver and lung cancers, HIV/AIDS, malaria, growth stunting and childhood malnutrition, and increased risk of adverse birth outcomes in Asia, Africa, and Central America.

To increase the ability to eliminate or reduce aflatoxin contamination, the mycotoxin biosynthetic pathway has been comprehensively studied. The pathway is composed of over 25 enzymatic steps, each step catalyzed by a different enzyme. 13 of these enzymes have been biochemically characterized in sufficient depth to allow the recent attribution of enzyme classification (EC) numbers.

EC numbers are part of a classification system managed by the International Union for Biochemistry and Molecular Biology (IUBMB). They are composed of 4 digits, which represent both the name of the enzyme and the precise description of the chemical reaction it catalyzes. In UniProtKB, enzymes are annotated with EC numbers (in ‘Names and origin’, ‘Protein names’, ‘Recommended name’, see for instance pksL1 entry), when these are available.

As of this release, the enzymes involved in aflatoxin biosynthesis have been manually annotated and are publicly available in UniProtKB/Swiss-Prot. The newly characterized enzymes from this pathway belong to oxidoreductase, transferase, hydrolase, and lyase classes of the EC classification system.

UniProtKB news

New human 1000 Genomes Project variants file

UniProt would like to announce the release of a new extension to the humsavar.txt variant catalogue. This new variant file, homo_sapiens_variation.txt.gz, supplements the set of manually curated human variants in humsavar.txt with a catalogue of novel Single Nucleotide Variants (SNVs or SNPs) from the 1000 Genomes Project for both UniProtKB/Swiss-Prot and UniProtKB/TrEMBL sequences. These variants have been automatically mapped to UniProtKB sequences, including isoform sequences, through Ensembl. In addition to defining the position and amino acid change due to each variant, the new file maps each affected UniProtKB record to the corresponding Ensembl gene, transcript and protein identifiers, provides the chromosomal location with allele change and, where possible, a cross-reference to OMIM is provided for the variant. This file along with the humsavar.txt file can now be found in the new dedicated ‘variants’ directory in the UniProt FTP site. We very much welcome the feedback of the community on our efforts. In future UniProt releases, we expect to add additional data sources for human variants that will include somatic variants, new data fields providing additional details concerning the variant and variants from additional species.

Cross-references to GuidetoPHARMACOLOGY

Cross-references have been added to GuidetoPHARMACOLOGY, which provides an expert-driven guide to pharmacological targets and the substances that act on them.

GuidetoPHARMACOLOGY is available at http://www.guidetopharmacology.org/

The format of the explicit links in the flat file is:

Resource abbreviation GuidetoPHARMACOLOGY
Resource identifier GuidetoPHARMACOLOGY identifier
Example Q08460:
DR   GuidetoPHARMACOLOGY; 380; -.

Show all the entries having a cross-reference to GuidetoPHARMACOLOGY.

New cross-reference category: Chemistry

A new database category has been added: Chemistry.

Change of the category of the cross-references BindingDB, ChEMBL and DrugBank

The BindingDB, ChEMBL and DrugBank databases have been moved from the category “Other” to the category “Chemistry”.

Changes to the controlled vocabulary of human diseases

New diseases:

Modified diseases:

Changes to keywords

New keywords:

Modified keyword:

Deleted keyword:

  • Inhibition of host TBK1-IKBKE-DDX3 complex by virus