Table 3.

Examples of computational and experimental discovery of unexpected functions in archaea.

COG numbers [37,38]	Function and comments	References
Computational predictions
0012, 1325, 1603, 1369, 0638, 1500, 1097, 689, 2123, 1996, 2136, 2892, 0618, 1782, 1096, 3286, 1761 and more	Archaeal exosome. Orthologs of eukaryotic exosome subunits form the largest conserved superoperon in archaea, after the ribosomal superoperon, suggesting the existence of a physical complex	[88]
1769, 1336, 3337, 1583, 1367, 1604, 1517, 1857, 1688, 1203, 1468, 1518, 2254, 1343, 1353, 1421, 1337, 1567, 1332, 4343	DNA repair system represented primarily in thermophiles	[59]
0358	Bacterial-type DNA primase (DnaG orthologs)	[24]
1311	Small subunit of euryarchaeal DNA polymerase II, predicted PHP family phosphohydrolase (probably phosphatase); eukaryotic homologs appear to be inactivated	[123]
1833	Uri superfamily endonuclease.	[136]
1628	Endonuclease V homologs.	K.S.M. and E.V.K., unpublished observations
1679,1786	Aconitase catalytic core and an interacting 'swiveling domain'	K.S.M. and E.V.K., unpublished observations
1711	Possible subunit of the DNA replication machinery	K.S.M. and E.V.K., unpublished observations
1310	Zn2+-dependent hydrolase homologous to the eukaryotic ubiquitin isopeptidase contained in the proteasome and COP9 signalosome	[137,138]
Computational predictions validated by experiments
1708	'Minimal' nucleotidyltransferases	[100,139]
1830	Fructose-1,6-bisphosphate aldolases (DhnA family)	[76,77]
1351	Thymidylate synthase	[61,64]
1685	Shikimate kinase (predicted on the basis of operon organization)	[140]
3635	Phosphoglycerate mutase	[24,141]
Experimental discovery of unexpected protein functions in archaea
1384	Class I lysyl-tRNA synthetase	[62]
1933	DNA polymerase II	[104]
1980	Fructose 1,6-bisphosphatase	[142]
1630	NurA, a novel 5'-3' nuclease encoded next to Rad50 and Mre11 orthologs; present in all sequenced archaeal genomes and some bacteria	[143] and K.S.M. and E.V.K., unpublished observations
1812	S-adenosylmethionine synthetase, was identified by mass tags	[144]
1591	Holliday junction resolvase	[101]
1581	Alba, a major DNA-binding chromatin protein in Crenarchaeota	[106]
1945	Pyruvoyl-dependent arginine decarboxylase (PvlArgDC), involved in polyamine biosynthesis	[145]