HGNC Approved Gene Symbol: USP44
Cytogenetic location: 12q22 Genomic coordinates (GRCh38) : 12:95,516,560-95,551,681 (from NCBI)
Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP44 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004).
By searching databases for sequences similar to USP family members, followed by PCR of human cDNA libraries, Quesada et al. (2004) cloned USP44. The deduced protein has an N-terminal zinc finger ubiquitin-binding (ZNF-UBP) domain, followed by a catalytic domain containing the cys box, QQD box, and his box characteristic of USP enzymes. Northern blot analysis detected a 4.4-kb transcript that was highly expressed in testis, but not in any other tissue examined.
Quesada et al. (2004) showed that recombinant USP44 could remove ubiquitin from a test protein.
Using a short hairpin RNA screen targeting components of the ubiquitin-proteasome pathway in human cells, Stegmeier et al. (2007) identified the deubiquitinating enzyme USP44 as a critical regulator of the spindle checkpoint. USP44 is not required for the initial recognition of unattached kinetochores and the subsequent recruitment of checkpoint components. Instead, it prevents the premature activation of the anaphase-promoting complex (APC) by stabilizing the APC-inhibitory Mad2-Cdc20 (601467, 603618) complex. USP44 deubiquitinates the APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts the APC-driven disassembly of Mad2-Cdc20 complexes. Stegmeier et al. (2007) concluded that a dynamic balance of ubiquitination by the APC and deubiquitination by USP44 contributes to the generation of the switch-like transition controlling anaphase entry, analogous to the way that phosphorylation and dephosphorylation of Cdk1 (116940) by Wee1 (193525) and Cdc25 (157680) controls entry into mitosis.
The International Radiation Hybrid Mapping Consortium mapped the USP44 gene to chromosome 12 (RH93395).
Quesada, V., Diaz-Perales, A., Gutierrez-Fernandez, A., Garabaya, C., Cal, S., Lopez-Otin, C. Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases. Biochem. Biophys. Res. Commun. 314: 54-62, 2004. [PubMed: 14715245] [Full Text: https://doi.org/10.1016/j.bbrc.2003.12.050]
Stegmeier, F., Rape, M., Draviam, V. M., Nalepa, G., Sowa, M. E., Ang, X. L., McDonald, E. R., III, Li, M. Z., Hannon, G. J., Sorger, P. K., Kirschner, M. W., Harper, J. W., Elledge, S. J. Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature 446: 876-881, 2007. [PubMed: 17443180] [Full Text: https://doi.org/10.1038/nature05694]