Rv2779c Family assigned · medium auto-curated

H37Rv Rv2779c · MTBC0 - · 179 aa · 3086215–3086754 (-) · RefSeq NP_217295.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Lrp/AsnC family transcriptional regulator
MTBC0 PGAP re-annotation
Revised (this work)Lrp/AsnC family transcriptional regulator. Pfam: HTH_24 (PF13412.13), HTH_AsnC-type (PF13404.13), AsnC_trans_reg (PF01037.29).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O33321 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional regulator AldR
Curated functionTranscriptional regulator that might play a role under hypoxic conditions (Probable). Regulates the expression of ald, which encodes L-alanine dehydrogenase. Serves as both an activator for ald expression in the presence of L-alanine and a repressor in the absence of L-alanine. Acts by binding directly to the upstream region of the ald gene. Four AldR-binding sites (O2, O1, O4 and O3) were identified upstream of the ald gene. O2, O1 and O4 are required for the induction of ald expression by alanine, while O3 is directly involved in the repression of ald expression, by occluding the access of R.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionAsnC family
Orthologous groupCOG1522

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 1.987 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.22% of strains (321) · clonal

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
HTH_24PF13412.13 8.1e-1632–79 Winged helix-turn-helix DNA-binding
HTH_AsnC-typePF13404.13 4.3e-1532–72 AsnC-type helix-turn-helix domain
AsnC_trans_regPF01037.29 6.9e-1695–172 Lrp/AsnC ligand binding domain

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

Closest characterised functional partner: ald (L-alanine dehydrogenase), medium confidence from genomic context alone (score 620 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2778c hyp hypothetical protein 774 774 ctx neighborhood:765
Rv0624 vapC30 ribonuclease VapC30 730 730 coexpression:730
Rv2780 ald L-alanine dehydrogenase 837 620 ctx neighborhood:618 textmining:589
Rv2777c hyp hypothetical protein 425 425 ctx neighborhood:421
Rv3557c kstR2 HTH-type transcriptional regulator KstR2 605 339 textmining:428
Rv3859c gltB glutamate synthase large subunit 518 220 textmining:408
Rv2272 transmembrane protein 692 152 textmining:652
Rv0880 HTH-type transcriptional regulator 858 102 textmining:849
Rv1219c raaS transcriptional regulator 679 89 textmining:663
Rv1218c tetronasin ABC transporter ATP-binding protein 527 75 textmining:510
Rv3549c short-chain type dehydrogenase/reductase 806 63 textmining:802
Rv3777 oxidoreductase 872 58 textmining:870
Rv0591 mce2C Mce family protein Mce2C 656 52 textmining:653
Rv1220c methyltransferase 634 52 textmining:630
Rv3489 hyp hypothetical protein 555 52 textmining:550

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): Lrp/AsnC family transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_24 PF13412.13 (E=8e-16), HTH_AsnC-type PF13404.13 (E=4e-15), AsnC_trans_reg PF01037.29 (E=7e-16)
  • (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_217295.2)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_24 (PF13412.13), HTH_AsnC-type (PF13404.13), AsnC_trans_reg (PF01037.29)
  • 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 COG1522
  • Curated reference: UniProt O33321 (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 — 21 functional partner(s); context anchor ald
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2779c|
MIILFRGHMRDNSTEHKTRRAASSKDVRPAELDEVDRRILSLLHGDARMPNNALADTVGIAPSTCHGRVRRLVDLGVIRGFYTDIDPVAVGLPLQAMISVNLQSSARGKIRSFIQQIRRKRQVMDVYFLAGADDFILHVAARDTEDLRSFVVENLNADADVAGTQTSLIFEHLRGAAPI