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UniProt release 2013_08

Published July 24, 2013


Girls just want to have … IFNE

Interferons (IFNs) are proteins made and released in answer to the presence of pathogens, such as viruses or bacteria, that trigger the protective defenses of the immune system. In other words, they “interfere” with infections, hence their name. Within the large IFN family, type I IFNs are clustered on a defined locus on chromosome 9p21 in humans and in a region of conserved synteny on chromosome 4 in mice. Their expression is induced by the activation of signaling pathways downstream of pattern-recognition receptors and they all bind to the IFN-alpha cell surface receptor complex consisting of IFNAR1 and IFNAR2 chains, leading to the expression of a whole set of genes.

There is, however, an alien on the type I IFN locus: IFN-epsilon (IFNE). IFNE shares less than 40% amino acid identity with bona fide type I IFNs, such as IFN-alpha or IFN-beta, but it does still bind to IFNAR, as expected for a type I IFN. However, unlike any of the other family members, it is not induced by the activation of any known pattern-recognition, including Toll-like receptor pathways. In addition, while other type I IFNs are mainly produced by haemopoietic cells, IFNE is constitutively expressed by epithelial cells of the female reproductive tract in humans and mice. At first glance, these observations seem to challenge a potential protective function for IFNE.

In a recent publication, Fung et al. reported that IFNE expression varied approximately 30-fold at different stages of the estrous cycle in the mouse uterus, with the highest levels at estrus (when estrogen levels are high) and was reduced during pregnancy (when progesterone levels are high). Similarly, in the human endometrium, IFNE levels were highest in the proliferative phase of the menstrual cycle and lowest in postmenopausal women (when estrogen levels are low). The suspected hormonal regulation could then be confirmed in mice and in humans: IFNE is induced by estrogens and reduced by progesterone. What about IFNE function? Fung et al. demonstrated that IFNE regulates IFN-regulated genes, including IRF7 and ISG15, as well as 2’5’oligoadenylate synthetase. What is more, Ifne-/- female mice, whose vaginas were infected with Chlamydia muridarum or herpes simplex virus 2, had more severe clinical disease than wild-type mice, as well as higher levels of virus or bacteria at defined time points after infection. Hence IFNE seems to play an important – though local – protective role against sexually transmitted infections.

These very interesting observations may have pinpointed the cause of susceptibility to infections of the reproductive tract in women on progesterone-containing contraception, i.e. a progesterone-induced decrease in IFNE expression.

In UniProtKB/Swiss-Prot, IFNE entries have been updated accordingly.

UniProtKB news

Cross-references to GeneWiki

Cross-references have been added to GeneWiki, an initiative that aims to create seed articles for every notable human gene.

GeneWiki is available at

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

Resource abbreviation GeneWiki
Resource identifier GeneWiki identifier
Example Q96N67:
DR   GeneWiki; Dock7; -.

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

Change of the cross-reference GlycoSuiteDB to UniCarbKB

GlycoSuiteDB, an annotated and curated relational database of glycan structures, has been integrated into UniCarbKB, with a new user interface and added functionalities.

We therefore changed the corresponding resource abbreviation from GlycoSuiteDB to UniCarbKB.

Example: P02763:

Previous flat file format:
DR   GlycoSuiteDB; P02763; -.
New flat file format:
DR   UniCarbKB; P02763; -.

UniProtKB/Swiss-Prot is currently linked to this resource from the cross-reference section (DR lines), but we also have some site-specific links from the sequence annotation section (FT CARBOHYD) of relevant UniProtKB/Swiss-Prot entries. An increase of the number of cross-linked entries is planned, including more literature based glycan data from UniCarbKB.

Removal of the cross-reference to GermOnline

Cross-references to GermOnline have been removed.

Changes to the controlled vocabulary of human diseases

New diseases: Modified diseases: Deleted diseases:
  • Cataract, congenital, cerulean type, 3
  • Cataract, congenital, non-nuclear polymorphic, autosomal dominant
  • Cataract, cortical, age-related, 2
  • Cataract-microcornea syndrome
  • Cataract, sutural, with punctate and cerulean opacities
  • Cataract, zonular
  • Hereditary non-polyposis colorectal cancer 3
  • Leukotriene C4 synthase deficiency
  • Neuropathy, congenital amyelinating
  • Pallido-ponto-nigral degeneration
  • Platyspondylic lethal skeletal dysplasia Sand Diego type
  • Thromboxane synthetase deficiency
  • Weaver syndrome 2

Changes to the controlled vocabulary for PTMs

New terms for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):
  • 5-glutamyl N2-arginine
  • 5-glutamyl N2-glutamate

Changes in subcellular location controlled vocabulary

New subcellular location:

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