TABLE 4.

Novel annotations transferred through structural similarity despite low sequence similarity^a

Rv no.	Top I-TASSER hit	AA%	TMADJ	PDB ID	Final annotation	Mycobrowser	UniProt	Mtb Network Portal	Type
Rv1139c	Integral membrane methyltransferase	18	0.86	4a2n	Putative integral membrane methyltransferase	Conserved hypothetical membrane protein	Conserved hypothetical membrane protein (membrane protein)	None	Novel
Rv1766c	Copper-sensing transcriptional repressor CsoR	29	0.84	4m1p	Putative transcription factor	Conserved protein	Conserved protein	None	Novel
Rv3192c	5,10-Methylenetetrahydromethanopterin reductase	16	0.83	1z69	Putative monooxygenase	Conserved hypothetical alanine- and proline-rich protein	Conserved hypothetical alanine- and proline-rich protein	Oxidoreductase	More specific
Rv2141c	M20 family metallopeptidase	20	0.82	2pok	Putative linear amide hydrolase	Conserved protein	Conserved protein	FIG016551: putative peptidase	Affirmatory
Rv1775	2,4-Diacetylphloroglucinol hydrolase	29	0.82	3hwp	Putative 3-oxo-carboxylic acid hydrolase	Conserved hypothetical protein	Uncharacterized protein	None	Novel
Rv0052c	Isonitrile hydratase	33	0.81	3noo	Putative hydrolyase/putative deglycase	Conserved protein	Conserved protein	ThiJ/PfpI family protein	Novel
Rv2036	Mycothiol-dependent maleylpyruvate isomerase	15	0.73	2nsg	Putative thiol-dependent DinB-like metalloenzyme	Conserved hypothetical protein	DinB family protein	None	More specific

^aSelected proteins with modeled structures highly similar to solved PDB structures of known function. Sequence similarities range in the “twilight zone” of sequence similarity, below which remote homology is undetectable by sequence similarity (132). A TM_ADJ above 0.52 indicates that the template and the underannotated gene share structural folds. Annotations from UniProt, Mtb Network Portal, and TubercuList are shown, along with the highest error-adjusted structural similarity match, its identifier (“PDB”), and final product annotation. “Affirmatory” indicates corroboration of the annotations in UniProt or Mtb Network Portal. “Novel” annotations are annotations entirely novel to those in UniProt and Mtb Network Portal, while “More specific” annotations are in accord with annotations in other databases but describe product function in greater detail.