Anaphase-promoting complex subunit 2 (ANAPC2)

The protein contains 822 amino acids for an estimated molecular weight of 93828 Da.

 

Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  2. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 37

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The reference OMIM entry for this protein is 606946

Anaphase-promoting complex, subunit 2; anapc2
Apc2
Kiaa1406

DESCRIPTION

ANAPC2 is 1 of several subunits of the anaphase-promoting complex (APC), which functions at the metaphase-to-anaphase transition of the cell cycle and is regulated by spindle checkpoint proteins. The APC is an E3 ubiquitin ligase that targets cell cycle regulatory proteins for degradation by the proteasome, thereby allowing progression through the cell cycle (summary by Jorgensen et al., 2001).

CLONING

By searching an EST database using frog APC peptide sequences, Yu et al. (1998) obtained full-length cDNAs encoding APC2, APC4 (606947), APC5 (606948), and APC7 (606949). The deduced 823-amino acid APC2 protein is similar to the cullin family of proteins (see CUL1; 603134), with which it shares a 200-residue cullin homology (CH) domain. Yu et al. (1998) suggested that the CH domain may perform similar biochemical functions in yeast and humans, such as binding ubiquitin or ubiquitin-conjugating enzymes. By screening for cDNAs with the potential to encode large proteins expressed in brain, Nagase et al. (2000) identified a cDNA encoding APC2, which they termed KIAA1406. RT-PCR analysis detected ubiquitous expression that was relatively strong in brain, kidney, and ovary. APC2 was expressed in all brain subregions tested, with highest levels in hippocampus, corpus luteum, amygdala, and substantia nigra.

GENE FUNCTION

Inversin (INVS; 243305) is a protein involved in embryonic patterning. Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Using transient expression experiments and a yeast 2-hybrid screen, Morgan et al. (2002) found evidence that inversin interacts with Apc2. Site-directed mutagenesis of the well-conserved D box residues abrogated inversin-Apc2 interaction. Dube et al. (2005) obtained 3-dimensional models of the human and Xenopus APC. They mapped CDH1 (FZR1; 603619) and APC2 to the same side of APC, implying that this is where substrates are ubiquitinated.

MAPPING

By radiation hybrid analysis, Nagase et al. (2000) mapped the APC2 gene to chromosome 9. ... More on the omim web site

Subscribe to this protein entry history

June 29, 2020: Protein entry updated
Automatic update: OMIM entry 606946 was added.

Feb. 22, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).