The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome.
One of the subunits of the APC that is required for ubiquitination activity is APC10, a one-domain protein homologous to a sequence element, termed the DOC domain, found in several hypothetical proteins that may also mediate ubiquitination reactions, because they contain combinations of either RING finger cullin or HECT domains [ (PUBMED:10318877) (PUBMED:11524682) (PUBMED:11884135) ].
The DOC domain consists of a beta-sandwich, in which a five-stranded antiparallel beta-sheet is packed on top of a three stranded antiparallel beta-sheet, exhibiting a 'jellyroll' fold [ (PUBMED:11524682) (PUBMED:11884135) ].
Proteins known to contain a DOC domain include:
Eucaryotic Doc1/Apc10.
Mammalian protein associated with the transcription factor Myc (PAM).
Mouse runty-jerky-sterile (RJS) protein.
Human HERC2, the ortholog of RJS.
Family alignment:
There are 4716 APC10 domains in 4712 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing APC10 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with APC10 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing APC10 domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until Sphase and prevents the premature expression of Cdc20p.
J Cell Biol. 2001; 154: 85-94
Display abstract
Cell cycle progression is driven by waves of cyclin expression coupled withregulated protein degradation. An essential step for initiating mitosis is theinactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APC(Cdh1) was proposedpreviously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK).Here, we demonstrate that in a normal cell cycle APC(Cdh1) is inactivated in agraded manner and is not extinguished until S phase. Complete inactivation ofAPC(Cdh1) requires S phase cyclins. Further, persistent APC(Cdh1) activitythroughout G1 helps to ensure the proper timing of Cdc20p expression. Thissuggests that S phase cyclins have an important role in allowing the accumulationof mitotic cyclins and further suggests a regulatory loop among S phase cyclins, APC(Cdh1), and APC(Cdc20).
Characterization of the DOC1/APC10 subunit of the yeast and the humananaphase-promoting complex.
J Biol Chem. 1999; 274: 14500-7
Display abstract
The anaphase-promoting complex/cyclosome (APC) is a ubiquitin-protein ligasewhose activity is essential for progression through mitosis. The vertebrate APCis thought to be composed of 8 subunits, whereas in budding yeast severaladditional APC-associated proteins have been identified, including a 33-kDaprotein called Doc1 or Apc10. Here, we show that Doc1/Apc10 is a subunit of theyeast APC throughout the cell cycle. Mutation of Doc1/Apc10 inactivates the APCwithout destabilizing the complex. An ortholog of Doc1/Apc10, which we callAPC10, is associated with the APC in different vertebrates, including humans and frogs. Biochemical fractionation experiments and mass spectrometric analysis of acomponent of the purified human APC show that APC10 is a genuine APC subunitwhose cellular levels or association with the APC are not cell cycle-regulated.We have further identified an APC10 homology region, which we propose to call theDOC domain, in several protein sequences that also contain either cullin or HECT domains. Cullins are present in several ubiquitination complexes including theAPC, whereas HECT domains represent the catalytic core of a different type ofubiquitin-protein ligase. DOC domains may therefore be important for reactionscatalyzed by several types of ubiquitin-protein ligases.
