Protein-glutamine deamidase Cif

UniProtKB accession:  Q63KH5

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UniProtKB description:  Protein-glutamine deamidase effector that inhibits the host cell cycle and other key cellular processes such as the actin network and programmed-cell death (PubMed:19308257, PubMed:20688984, PubMed:19225106). Acts by mediating the side chain deamidation of 'Gln-40' of host NEDD8, converting it to glutamate, thereby abolishing the activity of cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (PubMed:20688984, PubMed:21903097). Inactivation of CRL complexes prevents ubiquitination and subsequent degradation of the cyclin-dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40' of host NEDD8 also triggers macrophage-specific programmed cell death (PubMed:23175788). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (PubMed:20688984). Also regulates the host NF-kappa-B signaling via activation of MAPK/ERK cascade: activation of host MAPK/ERK cascade is independent of CRL complexes inhibition, suggesting that Cif has other host protein targets than NEDD8 (PubMed:28166272, PubMed:29848489).