TsaB, previously known as YeaZ, has been shown to be involved in N6-threonylcarbamoyladenonsine (t(6)A) biosynthesis, together with YgjD (TsaD), YrdC (TsaC), and YjeE (TsaE) [, ].
This entry represents the threonylcarbamoyl-AMP synthase, includding RimN or YrdC (also known as TsaC) [], which is involved in the biosynthesis of N6-threonyl-carbamoyl-adenosine (t6A) modified tRNA. This is a universal modification, found at position 37 of ANN decoding tRNAs. Analysis shows that YrdC binds ATP and preferentially binds tRNA-Thr lacking the t6A modification []. Furthermore YrdC has been shown to have threonine-dependent ATPase activity that generates AMP []. YrdC (TsaC) and proteins YgjD (TsaD), YjeE (TsaE), and YeaZ (TsaB), are necessary and sufficient for t6A biosynthesis in vitro, and may constitute a complex.
This group contains homologues of Escherichia coli YrdC with an additional unique short (~100 aa) C-terminal domain. In accordance with its proposed role as a translation factor, YrdC preferentially binds dsRNA, likely via a depression on the surface of the protein []. However, members of both this group lack the C-terminal domain that has been shown to be essential for the regulatory (probably translational) function of the related two-domain protein SUA5 () [].
This superfamily represents a structural domain consisting of segregated alpha and beta regions in 3-layers. Homologous domains with this structure are found in:3,4-dihydroxy-2-butanone 4-phosphate synthase () (DHBP synthase) (RibB) A family of eukaryotic and prokaryotic hypothetical proteins that includes YrdC and YciO from Escherichia coli and MTH1692 from the archaea Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum)DHBP synthase RibB catalyses the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate, the latter serving as the biosynthetic precursor for the xylene ring of riboflavin []. In Photobacterium leiognathi, the riboflavin synthesis genes ribB (DHBP synthase), ribE (riboflavin synthase), ribH (lumazone synthase) and ribA (GTP cyclohydrolase II) all reside in the lux operon []. RibB is sometimes found as a bifunctional enzyme with GTP cyclohydrolase II that catalyses the first committed step in the biosynthesis of riboflavin (). No sequences with significant homology to DHBP synthase are found in the metazoa.The YrdC family of hypothetical proteins are widely distributed in eukaryotes and prokaryotes and occur as: (i) independent proteins, (ii) with C-terminal extensions, and (iii) as domains in larger proteins, some of which are implicated in regulation []. YrdC from Escherichia coli preferentially binds to double-stranded RNA and DNA. YrdC is predicted to be an rRNA maturation factor, as deletions in its gene lead to immature ribosomal 30S subunits and, consequently, fewer translating ribosomes []. Therefore, YrdC may function by keeping an rRNA structure needed for proper processing of 16S rRNA, especially at lower temperatures. Threonylcarbamoyl-AMP synthase (Sua5) is an example of a multi-domain protein that contains an N-terminal YrdC-like domain and a C-terminal Sua5 domain. Sua5 was identified in Saccharomyces cerevisiae (Baker's yeast) as a suppressor of a translation initiation defect in the cytochrome c gene and is required for formation of a threonylcarbamoyl group on adenosine at position 37 in tRNAs [, ]. HypF is involved in the synthesis of the active site of [NiFe]-hydrogenases [].
This entry represents the TsaD protein family that is widely distributed. TsaD and its archaeal homologue Kae1 () belong to the Kae1/TsaD family (), a conserved protein family with unknown function.This entry includes bacterial TsaD and its homologues, such as Qri7 (localize to the mitochondria) from budding yeast []. TsaD (also known as Gcp or YgjD) was originally described as a glycoprotease essential for cell viability []and a critical mediator involved in the modification of cell wall peptidoglycan synthesis and/or cell division []. Gcp is a member of the Kae1/TsaD family, required for the formation of a threonylcarbamoyl group on adenosine at position 37 in tRNAs that read codons beginning with adenine []. YgjD has been renamed as TsaD, and it has been shown that YgjD and proteins YrdC (TsaC), YjeE (TsaE), and YeaZ (TsaB), are necessary and sufficient for t6A biosynthesis in vitro, and may constitute a complex [].The first characterised member of the Kae1/TsaD family was annotated as Gcp for O-sialoglycoprotein endopeptidase [], but this activity could not be confirmed []. Later, its homologue, Kae1 from Pyrococcus abyssi, has been shown to have DNA-binding properties and apurinic-endonuclease activity []. Members of this family have since been studied in yeast, archaea and bacteria resulting in sometimes conflicting data, several proposed functions and annotations but no definitive characterisation. For instance, some members have been linked to DNA maintenance in bacteria and mitochondria []and transcription regulation and telomere homeostasis in eukaryotes [, ], but their function remained unclear. Recent research indicates that this family is involved in the biosynthesis of N6-threonylcarbamoyl adenosine, a universal modification found at position 37 of tRNAs that read codons beginning with adenine [].
