Reaction: (1) ATP + a [protein]-L-serine = diphosphate + a [protein]-O-(5′-adenylyl)-L-serine
(1) ATP + a [protein]-L-threonine = diphosphate + a [protein]-O-(5′-adenylyl)-L-threonine
(1) ATP + a [protein]-L-tyrosine = diphosphate + a [protein]-O-(5′-adenylyl)-L-tyrosine
Other name(s): AMPylase; selO (gene name); FMP40 (gene name); SELENOO (gene name); IbpA; VopS; DrrA; FICD (gene name)
Systematic name: [protein] L-serine/L-threonine/L-tyrosine adenylyltransferase
Comments: The enzyme, commonly referred to as AMPylase, transfers an adenylyl (adenosine 5'-phosphate) group from ATP to L-serine, L-threonine, and L-tyrosine residues in its target protein substrates. AMPylation is found in both prokaryotes and eukaryotes. In bacteria AMPylases are abundant enzymes that either regulate the function of endogenous bacterial proteins or are translocated into host cells to hijack host cell signalling processes. Metazoans AMPylases are either enzymes containing a conserved Fic domain that primarily modify the ER-resident chaperone BiP, or mitochondrial selenocysteine-containing proteins (SelO) involved in redox signalling.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Xiao, J., Worby, C.A., Mattoo, S., Sankaran, B. and Dixon, J.E. Structural basis of Fic-mediated adenylylation. Nat. Struct. Mol. Biol. 17 (2010) 1004-1010. [PMID: 20622875]
2. Palanivelu, D.V., Goepfert, A., Meury, M., Guye, P., Dehio, C. and Schirmer, T. Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA. Protein Sci. 20 (2011) 492-499. [PMID: 21213248]
3. Truttmann, M.C., Cruz, V.E., Guo, X., Engert, C., Schwartz, T.U. and Ploegh, H.L. The Caenorhabditis elegans protein FIC-1 is an AMPylase that covalently modifies heat-shock 70 family proteins, translation elongation factors and histones. PLoS Genet. 12 (2016) e1006023. [PMID: 27138431]
4. Sreelatha, A., Yee, S.S., Lopez, V.A., Park, B.C., Kinch, L.N., Pilch, S., Servage, K.A., Zhang, J., Jiou, J., Karasiewicz-Urbanska, M., Lobocka, M., Grishin, N.V., Orth, K., Kucharczyk, R., Pawlowski, K., Tomchick, D.R. and Tagliabracci, V.S. Protein AMPylation by an evolutionarily conserved pseudokinase. Cell 175 (2018) 809-821. [PMID: 30270044]
5. Bardwell, L. Pseudokinases: Flipping the ATP for AMPylation. Curr. Biol. 29 (2019) R23-R25. [PMID: 30620911]
6. Chatterjee, B.K. and Truttmann, M.C. Fic and non-Fic AMPylases: protein AMPylation in metazoans. Open Biol 11 (2021) 210009. [PMID: 33947243]