cobB Resolved · high auto-curated

H37Rv Rv1151c · MTBC0 mtbc0_001237 · 237 aa · 1287345–1288058 (-) · RefSeq NP_215667.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NAD-dependent protein deacylase
MTBC0 PGAP re-annotationNAD-dependent protein deacylase
Revised (this work)NAD-dependent protein deacylase. Pfam: SIR2 (PF02146.24).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WGG3 SwissProt · reviewed · Evidence at protein level
UniProt nameNAD-dependent protein deacylase
EC (curated) EC 2.3.1.286
Curated functionNAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated form..; FUNCTION: Reactivates acetylated acetyl-CoA synthetase (ACS) through an NAD-dependent deacetylation. Is able to auto-ADP-ribosylate. Deacetylates acetylated HupB..; FUNCTION: Probably desuccinylates succinylated HupB..; FUNCTION: Involved in non-homologous end joining (NHEJ) repair of blunt, 5' overhang and 3' overhang DNA double strand breaks (DSB).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namecobB
eggNOG descriptionNAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated form
Orthologous groupCOG0846
KEGG orthology K12410
Gene Ontology (59) GO:0000726, GO:0003674, GO:0003824, GO:0003953, GO:0005575, GO:0005618, GO:0005623, GO:0006139, GO:0006259, GO:0006281, GO:0006302, GO:0006303 +47 more

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 0.331 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 missense, 0 nonsense, 0 frameshift

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)

PfamAccessioni-EvalueResiduesDescription
SIR2PF02146.24 8.5e-578–184 Sir2 family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv1152 (transcriptional regulator), high confidence from genomic context alone (score 923 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0212c nadR transcriptional regulator NadR 984 984 coexpression:845 database:900
Rv2438c nadE glutamine-dependent NAD(+) synthetase 963 926 database:900 textmining:529
Rv1152 transcriptional regulator 923 923 ctx neighborhood:789 coexpression:651
Rv2043c pncA pyrazinamidase/nicotinamidase PncA 927 917 database:900
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 947 915 database:900 textmining:408
Rv2713 sthA pyridine nucleotide transhydrogenase 919 914 database:900
Rv3199c nudC NADH pyrophosphatase 941 912 database:900
Rv1695 ppnK inorganic polyphosphate/ATP-NAD kinase 923 906 database:900
Rv3307 deoD purine nucleoside phosphorylase 935 904 database:900
Rv3393 iunH nucleoside hydrolase 909 904 database:900
Rv0156 pntAb NAD(P) transhydrogenase subunit alpha PntAb 909 904 database:900
Rv0155 pntAa NAD(P) transhydrogenase subunit alpha PntAa 909 904 database:900
Rv0157 pntB NAD(P) transhydrogenase subunit beta PntB 904 904 database:900
Rv3840 transcriptional regulator 862 862 coexpression:860
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 866 861 coexpression:861

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: NAD-dependent protein deacylase
  • MTBC0 PGAP product: NAD-dependent protein deacylase
  • Pfam (hmmscan --cut_ga): SIR2 PF02146.24 (E=8e-57)
  • (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_215667.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SIR2 (PF02146.24)
  • 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 COG0846
  • Curated reference: UniProt P9WGG3 (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 — 164 functional partner(s); context anchor Rv1152
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001237|Rv1151c|cobB
MRVAVLSGAGISAESGVPTFRDDKNGLWARFDPYELSSTQGWLRNPERVWGWYLWRHYLVANVEPNDGHRAIAAWQDHAEVSVITQNVDDLHERAGSGAVHHLHGSLFEFRCARCGVPYTDALPEMPEPAIEVEPPVCDCGGLIRPDIVWFGEPLPEEPWRSAVEATGSADVMVVVGTSAIVYPAAGLPDLALARGTAVIEVNPEPTPLSGSATISIRESASQALPGLLERLPALLK