SMART: RelA_SpoT domain annotation

RelA_SpoT Region found in RelA / SpoT proteins

SMART accession number:	SM00954
Description:	The functions of Escherichia coli RelA and SpoT differ somewhat. RelA produces pppGpp (or ppGpp) from ATP and GTP (or GDP). SpoT degrades ppGpp, but may also act as a secondary ppGpp synthetase. The two proteins are strongly similar. In many species, a single homolog to SpoT and RelA appears reponsible for both ppGpp synthesis and ppGpp degradation. (p)ppGpp is a regulatory metabolite of the stringent response, but appears also to be involved in antibiotic biosynthesis in some species.
Interpro abstract (IPR007685):	This entry includes the catalytic domains of Escherichia coli ppGpp synthetase (RelA), ppGpp synthetase/hydrolase (SpoT), and related proteins. The functions of Escherichia coli RelA and SpoT differ somewhat. RelA ( EC 2.7.6.5 ) produces pppGpp (or ppGpp) from ATP and GTP (or GDP) in response to amino-acid starvation and in association with ribosomes [ (PUBMED:2844820) ]. SpoT ( EC 3.1.7.2 ) degrades ppGpp, but may also act as a secondary ppGpp synthetase under carbon limitation in a ribosome-independent manner [ (PUBMED:8730877) (PUBMED:8648647) ]. Gram-negative bacteria have two enzymes involved in (p)ppGpp metabolism while most Gram-positive organisms have a single Rel-Spo enzyme (Rel), which both synthesizes and degrades (p)ppGpp [ (PUBMED:12003927) (PUBMED:8631718) ]. The Arabidopsis thaliana Rel-Spo proteins, At-RSH1, At-RSH2, and At-RSH3 appear to regulate a rapid (p)ppGpp-mediated response to pathogens and other stresses [ (PUBMED:10725385) ]. This catalytic domain is found in association with an N-terminal HD domain and a C-terminal metal dependent phosphohydrolase domain (TGS). Some Rel-Spo proteins also have a C-terminal regulatory ACT domain. This subgroup belongs to the Pol beta-like NT superfamily [ (PUBMED:10075991) (PUBMED:7482698) ]. (p)ppGpp is a regulatory metabolite of the stringent response [ (PUBMED:16554711) ], but appears also to be involved in antibiotic biosynthesis in some species [ (PUBMED:9531539) ]. In the Pol beta-like NT superfamily [ (PUBMED:10075991) (PUBMED:7482698) ], the majority of enzymes have two carboxylates, Dx[D/E], together with a third more distal carboxylate, which coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. These carboxylate residues are fairly well conserved in this family.
GO process:	guanosine tetraphosphate metabolic process (GO:0015969)
Family alignment:	View or

There are 35291 RelA_SpoT domains in 35288 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing RelA_SpoT domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with RelA_SpoT domain is also avaliable.

Click on the protein counts, or double click on taxonomic names to display all proteins containing RelA_SpoT domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, Cashel M
- Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA nullmutants can be eliminated by spoT null mutations.
- J Biol Chem. 1991; 266: 5980-90
- Display abstract
- It was known previously that 1) the relA gene of Escherichia coli encodesan enzyme capable of guanosine 3',5'-bispyrophosphate (ppGpp) synthesis,2) an uncharacterized source of ppGpp synthesis exists in relA nullstrains, and 3) cellular degradation of ppGpp is mainly due to amanganese-dependent ppGpp 3'-pyrophosphohydrolase encoded by the spoTgene. Here, the effects of spoT gene insertions and deletions are comparedwith analogous alterations in neighboring genes in the spo operon andfound to be lethal in relA+ strains as well as slower growing in relAlbackgrounds than delta relA hosts. Cells with null alleles in both therelA and spoT genes are found no longer to accumulate ppGpp after glucoseexhaustion or after chelation of manganese ions by picolinic acidaddition; the inability to form ppGpp is reversed by a minimal spoT geneon a multicopy plasmid. Strains apparently lacking ppGpp show a complexphenotype including auxotrophy for several amino acids and morphologicalalterations. We propose that the SpoT protein can either catalyze orcontrol the alternative pathway of ppGpp synthesis in addition to itsknown role as a (p)ppGpp 3'-pyrophosphohydrolase. We favor the possibilitythat the SpoT protein is a bifunctional enzyme capable of catalyzingeither ppGpp synthesis or degradation.
Structure (3D structures containing this domain)

Links (links to other resources describing this domain)
PFAM RelA_SpoT
INTERPRO IPR007685

PDB code	Main view	Title
1vj7		Crystal structure of the bifunctional catalytic fragment of RelSeq, the RelA/SpoT homolog from Streptococcus equisimilis.
2be3		Structure of a GTP Pyrophosphokinase Family Protein from Streptococcus pneumoniae
3l9d		The Crystal Structure of smu.1046c from Streptococcus mutans UA159
5dec		5DEC
5ded		5DED
5f2v		5F2V
5iqr		5IQR
5kps		5KPS
5kpv		5KPV
5kpw		5KPW
5kpx		5KPX
5l3p		5L3P

PFAM	RelA_SpoT
INTERPRO	IPR007685

RelA_SpoT

Taxonomic distribution of proteins containing RelA_SpoT domain.

3D Structures of RelA_SpoT domains in PDB