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UniProt release 2018_04

Published April 25, 2018


The Matrix (enzymes) Reloaded

Collagen is the major protein that stitches together animal tissues, and is the most abundant protein in mammals, making up to 25-35% of our body weight. It comprises three individual protein molecules which coil together to form tropocollagen fibers which in turn make microfibrils. Collagen is extremely stable and extremely ancient; collagen fragments have been sequenced from 80 million year old dinosaurs, such as Brachylophosaurus canadensis and Tyrannosaurus rex, and is found in all extant metazoans. The breakdown of collagen is essential to permit tissue growth, and all animals have the ability to metabolize collagen in a very controlled way by cutting a single site. Infectious bacteria, such as gas gangrene-causing Clostridium perfringens and Hathewaya histolytica, on the other hand digest collagen indiscriminately, using collagenases with both endopeptidase and tripeptidylcarboxypeptidase activities. This rampant activity causes massive tissue disruption, favoring bacterial colonization and virulence, and is obviously severely problematic in a clinical setting.

Despite their different approaches to collagen degradation (cautious versus gung-ho), mammalian and clostridial collagenases have similar enzymatic mechanisms and many inhibitors work on both types of collagenases, making them unsuitable for antibacterial therapy. Recent work by Schönauer et al. has found promising new molecules that inhibit only bacterial and not mammalian collagenases, pointing to a possible way to block bacterial collagenase action in a wound setting for example. By not attacking the bacteria directly, these inhibitors should provide novel, non-selective ways to treat some of the damage inflicted by these bacteria, while minimizing potential resistance. While these inhibitors are undoubtedly very useful, there are also many applications in which potentially undesirable bacterial collagenase activities are actively exploited. The H.histolytica collagenases (ColG and ColH) are used to isolate pancreatic islet cells for transplantation, remove retained placenta in cattle and horses, to debride wounds, ulcers and severely burned patients (SANTYL Ointment, Smith and Nephew, Inc.), and to treat human diseases caused by abnormal accumulation of collagen plaques such as Dupuytren's disease and Peyronie's disease (Xiaflex, Endo Pharmaceuticals, Inc.). Dupuytren's disease is an abnormal deposition of collagen in the hand that causes permanent contraction. In Peyronie's disease, collagen forms fibrous plaques in the penis, restricting erection. Collagenase injection relieves this accumulation, leading to an increased quality of life. The collagen-binding domain of collagenases when attached to other proteins, promotes their retention at injection sites for as long as 10 days. Although this is far from the only example of a repurposed enzyme (think of Botox, another clostridial protein), it is fascinating how a protein class that can be so dangerous to life, when harnessed, can be so very helpful.

As of this release 3 clostridial collagenases have been expertly updated in UniProtKB/Swiss-Prot.

Cross-references to GlyConnect

Cross-references have been added to the GlyConnect database and protein glycosylation platform.

GlyConnect is available at

The format of the explicit links is:

Resource abbreviationGlyConnect
Resource identifierResource identifier

Example: P00742

Show all entries having a cross-reference to GlyConnect.

Cross-references to GlyConnect may be isoform-specific. The general format of isoform-specific cross-references was described in release 2014_03.

Text format

Example: P00742

DR   GlyConnect; 102; -.

XML format

Example: P00742

<dbReference type="GlyConnect" id="102"/>

RDF format

Example: P00742

  rdfs:seeAlso <> .
  rdf:type up:Resource ;
  up:database <> .

Changes to the controlled vocabulary of human diseases

New diseases:

Modified diseases:

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