Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional (p)ppGpp synthase/hydrolase RelA |
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| MTBC0 PGAP re-annotation | RelA/SpoT family protein |
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| Revised (this work) | RelA/SpoT family protein. Pfam: HD_4 (PF13328.13), HD (PF01966.29), RelA_SpoT (PF04607.24), TGS (PF02824.28), RelA_AH (PF19296.6), RelA_RIS (PF28438.1), ACT_4 (PF13291.13), ACT (PF01842.32). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHG9
SwissProt · reviewed
· Evidence at protein level
|
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| UniProt name | Bifunctional |
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| EC (curated) |
EC 2.7.6.5, EC 3.1.7.2
|
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| Curated function | In eubacteria ppGpp (guanosine 3'-diphosphate 5'-diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. This enzyme catalyzes both the formation of pppGpp, which is then hydrolyzed to form ppGpp, as well as the hydrolysis of ppGpp. RelA is probably a key factor in the pathogenesis of M.tuberculosis as it regulates the intracellular concentrations of (p)ppGpp. |
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Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
T Signal transduction mechanisms
|
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| Preferred name | relA |
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| eggNOG description | In eubacteria ppGpp (guanosine 3'-diphosphate 5-' diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance |
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| Orthologous group | COG0317 |
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| EC number |
EC 2.7.6.5, EC 3.1.7.2
|
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| KEGG orthology |
K00951, K01139
|
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| KEGG pathways |
map00230
|
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| Gene Ontology (110) |
GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006139, GO:0006163, GO:0006164, GO:0006725, GO:0006753 +98 more
|
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Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are
computed annotations, not manual curation; cross-check against the primary literature
before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS |
0.29 · purifying
|
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| Polymorphic sites (≥ 0.1% of strains) |
7 synonymous, 6 missense, 0 nonsense, 0 frameshift
|
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pN/pS from segregating SNPs (singletons removed) normalised by possible sites.
Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene).
A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic
variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A
clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a
convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
HD_4 | PF13328.13 |
5.3e-45 | 86–233 |
HD domain |
HD | PF01966.29 |
8.1e-15 | 105–202 |
HD domain |
RelA_SpoT | PF04607.24 |
1.2e-42 | 293–403 |
Region found in RelA / SpoT proteins |
TGS | PF02824.28 |
1.9e-24 | 452–511 |
TGS domain |
RelA_AH | PF19296.6 |
1.2e-15 | 539–609 |
RelA/SpoT AH domain |
RelA_RIS | PF28438.1 |
8.3e-23 | 644–704 |
RelA/SpoT RIS domain |
ACT_4 | PF13291.13 |
4.8e-17 | 709–785 |
ACT domain |
ACT | PF01842.32 |
6.6e-13 | 714–778 |
ACT domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0053 rpsF |
30S ribosomal protein S6 |
940 |
925 |
experimental:903 |
Rv2442c rplU |
50S ribosomal protein L21 |
916 |
917 |
experimental:903 |
Rv0720 rplR |
50S ribosomal protein L18 |
919 |
916 |
experimental:903 |
Rv0704 rplB |
50S ribosomal protein L2 |
924 |
915 |
experimental:903 |
Rv1617 pykA |
pyruvate kinase |
921 |
915 |
database:900 |
Rv1389 gmk |
guanylate kinase |
924 |
914 |
database:900 |
Rv1625c cya |
adenylate cyclase |
912 |
913 |
database:900 |
Rv1026 ppx2 hyp |
hypothetical protein |
939 |
912 |
database:900 |
Rv0496 ppx1 hyp |
hypothetical protein |
939 |
912 |
database:900 |
Rv0721 rpsE |
30S ribosomal protein S5 |
919 |
912 |
experimental:903 |
Rv0719 rplF |
50S ribosomal protein L6 |
928 |
911 |
experimental:911 |
Rv1643 rplT |
50S ribosomal protein L20 |
914 |
911 |
experimental:903 |
Rv3443c rplM |
50S ribosomal protein L13 |
951 |
908 |
experimental:903 textmining:493 |
Rv1642 rpmI |
50S ribosomal protein L35 |
910 |
908 |
experimental:903 |
Rv0682 rpsL |
30S ribosomal protein S12 |
919 |
907 |
experimental:903 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression,
experimental, database, text-mining) into a 0–1000 score. The ctx
badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion,
phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an
unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not
depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with
the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: bifunctional (p)ppGpp synthase/hydrolase RelA
- MTBC0 PGAP product: RelA/SpoT family protein
- Pfam (hmmscan --cut_ga): HD_4 PF13328.13 (E=5e-45), HD PF01966.29 (E=8e-15), RelA_SpoT PF04607.24 (E=1e-42), TGS PF02824.28 (E=2e-24), RelA_AH PF19296.6 (E=1e-15), RelA_RIS PF28438.1 (E=8e-23), ACT_4 PF13291.13 (E=5e-17), ACT PF01842.32 (E=7e-13)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024),
An imputed ancestral reference genome for the MTBC,
doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217099.1)
- Domains: Pfam-A via hmmscan --cut_ga — HD_4 (PF13328.13), HD (PF01966.29), RelA_SpoT (PF04607.24), TGS (PF02824.28), RelA_AH (PF19296.6), RelA_RIS (PF28438.1), ACT_4 (PF13291.13), ACT (PF01842.32)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0317
- Curated reference: UniProt
P9WHG9
(SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of
145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
157 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002750|Rv2583c|relA
MAEDQLTAQAVAPPTEASAALEPALETPESPVETLKTSISASRRVRARLARRMTAQRSTTNPVLEPLVAVHREIYPKADLSILQRAYEVADQRHASQLRQSGDPYITHPLAVANILAELGMDTTTLVAALLHDTVEDTGYTLEALTEEFGEEVGHLVDGVTKLDRVVLGSAAEGETIRKMITAMARDPRVLVIKVADRLHNMRTMRFLPPEKQARKARETLEVIAPLAHRLGMASVKWELEDLSFAILHPKKYEEIVRLVAGRAPSRDTYLAKVRAEIVNTLTASKIKATVEGRPKHYWSIYQKMIVKGRDFDDIHDLVGVRILCDEIRDCYAAVGVVHSLWQPMAGRFKDYIAQPRYGVYQSLHTTVVGPEGKPLEVQIRTRDMHRTAEYGIAAHWRYKEAKGRNGVLHPHAAAEIDDMAWMRQLLDWQREAADPGEFLESLRYDLAVQEIFVFTPKGDVITLPTGSTPVDFAYAVHTEVGHRCIGARVNGRLVALERKLENGEVVEVFTSKAPNAGPSRDWQQFVVSPRAKTKIRQWFAKERREEALETGKDAMAREVRRGGLPLQRLVNGESMAAVARELHYADVSALYTAIGEGHVSAKHVVQRLLAELGGIDQAEEELAERSTPATMPRRPRSTDDVGVSVPGAPGVLTKLAKCCTPVPGDVIMGFVTRGGGVSVHRTDCTNAASLQQQAERIIEVLWAPSPSSVFLVAIQVEALDRHRLLSDVTRALADEKVNILSASVTTSGDRVAISRFTFEMGDPKHLGHLLNAVRNVEGVYDVYRVTSAA
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