InterPro domain: IPR004939

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 [ 1 ].

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 (see PDOC00449 ), cullin (see PDOC00967 ) or HECT (see PDOC50237 ) domains [ 2 , 3 , 4 ].

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 [ 5 , 5 ].

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.

1. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133, 653-65
2. Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. J. Biol. Chem. 274, 14500-7
3. Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex. Nat. Struct. Biol. 8, 784-8
4. Implications for the ubiquitination reaction of the anaphase-promoting complex from the crystal structure of the Doc1/Apc10 subunit. J. Mol. Biol. 316, 955-68