Alternative titles; symbols
HGNC Approved Gene Symbol: ANAPC2
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:137,174,784-137,188,560 (from NCBI)
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).
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.
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.
Wang et al. (2020) reported that the host E3 ubiquitin ligase ANAPC2, a core subunit of the anaphase-promoting complex/cyclosome, interacts with the mycobacterial protein Rv0222 and promotes the attachment of lys11-linked ubiquitin chains to lys76 of Rv0222 in order to suppress the expression of proinflammatory cytokines. Inhibition of ANAPC2 by specific shRNA abolished the inhibitory effect of Rv0222 on proinflammatory responses. Moreover, mutation of the ubiquitination site on Rv0222 impaired the inhibition of proinflammatory cytokines by Rv0222 and reduced virulence during infection in mice. Mechanistically, lys11-linked ubiquitination of Rv0222 by ANAPC2 facilitates the recruitment of the protein tyrosine phosphatase SHP1 (PTPN6; 176883) to the adaptor protein TRAF6 (602355), preventing the lys63-linked ubiquitination and activation of TRAF6.
By radiation hybrid analysis, Nagase et al. (2000) mapped the APC2 gene to chromosome 9.
Stumpf (2020) mapped the ANAPC2 gene to chromosome 9q34.3 based on an alignment of the ANAPC2 sequence (GenBank BC032503) with the genomic sequence (GRCh38).
Dube, P., Herzog, F., Gieffers, C., Sander, B., Riedel, D., Muller, S. A., Engel, A., Peters, J.-M., Stark, H. Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C. Molec. Cell 20: 867-879, 2005. [PubMed: 16364912] [Full Text: https://doi.org/10.1016/j.molcel.2005.11.008]
Jorgensen, P. M., Graslund, S., Betz, R., Stahl, S., Larsson, C., Hoog, C. Characterisation of the human APC1, the largest subunit of the anaphase-promoting complex. Gene 262: 51-59, 2001. [PubMed: 11179667] [Full Text: https://doi.org/10.1016/s0378-1119(00)00511-4]
Morgan, D., Eley, L., Sayer, J., Strachan, T., Yates, L. M., Craighead, A. S., Goodship, J. A. Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. Hum. Molec. Genet. 11: 3345-3350, 2002. [PubMed: 12471060] [Full Text: https://doi.org/10.1093/hmg/11.26.3345]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 65-73, 2000. [PubMed: 10718198] [Full Text: https://doi.org/10.1093/dnares/7.1.65]
Stumpf, A. M. Personal Communication. Baltimore, Md. 06/22/2020.
Wang, L., Wu, J., Li, J., Yang, H., Tang, T., Liang, H., Zuo, M., Wang, J., Liu, H., Liu, F., Chen, J., Liu, Z., Wang, Y., Peng, C., Wu, X., Zheng, R., Huang, X., Ran, Y., Rao, Z., Ge, B. Host-mediated ubiquitination of a mycobacterial protein suppresses immunity. Nature 577: 682-688, 2020. [PubMed: 31942069] [Full Text: https://doi.org/10.1038/s41586-019-1915-7]
Yu, H., Peters, J.-M., King, R. W., Page, A. M., Hieter, P., Kirschner, M. W. Identification of a cullin homology region in a subunit of the anaphase-promoting complex. Science 279: 1219-1222, 1998. [PubMed: 9469815] [Full Text: https://doi.org/10.1126/science.279.5354.1219]