Rv1048c Still unknown · low auto-curated

H37Rv Rv1048c · MTBC0 mtbc0_001124 · 371 aa · 1178377–1179492 (-) · RefSeq NP_215564.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 4rgu-assembly1_A-2 Crystal Structure of Putative MarR Family Transcrip (prob 0.95, TM 0.60).

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

Curated reference (UniProt)

UniProt P96353 TrEMBL · unreviewed · Evidence at protein level
UniProt nameUncharacterized protein

UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein conserved in bacteria
Orthologous groupCOG4861

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 0.804 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 88.9 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
4rgu-assembly1_A-2 0.95 0.60 1.3e-01 4rgu-assembly1_A-2 Crystal Structure of Putative MarR Family Transcriptional Regulator HcaR from Acinetobacter sp. ADP complexed with ferulic acid
5kk1-assembly1_A 0.90 0.61 2.2e-01 5kk1-assembly1_A Structure of pNOB8 AspA-DNA complex.
3k0l-assembly1_B 0.90 0.60 2.1e-01 3k0l-assembly1_B Crystal Structure of Putative MarR Family Transcriptional Regulator from Acinetobacter sp. ADP
3g3z-assembly1_B 0.90 0.63 3.1e-01 3g3z-assembly1_B The structure of NMB1585, a MarR family regulator from Neisseria meningitidis
3bj6-assembly1_B 0.89 0.62 3.3e-01 3bj6-assembly1_B Crystal structure of MarR family transcription regulator SP03579
2ve9-assembly1_B 0.87 0.72 5.5e-01 2ve9-assembly1_B Xray structure of KOPS bound gamma domain of FtsK (P. aeruginosa)
3nrv-assembly2_D 0.87 0.63 3.7e-01 3nrv-assembly2_D Crystal structure of MarR/EmrR family transcriptional regulator from Acinetobacter sp. ADP1
4rgu-assembly1_B-2 0.82 0.55 2.0e-01 4rgu-assembly1_B-2 Crystal Structure of Putative MarR Family Transcriptional Regulator HcaR from Acinetobacter sp. ADP complexed with ferulic acid

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

Closest characterised functional partner: Rv1049 (transcriptional repressor), medium confidence from genomic context alone (score 483 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1049 transcriptional repressor 570 483 ctx neighborhood:469
Rv2528c mrr restriction system protein 575 100 textmining:547
Rv3833 AraC family transcriptional regulator 494 70 textmining:479
Rv0326 hyp hypothetical protein 635 55 textmining:630
Rv0327c cyp135A1 cytochrome P450 Cyp135A1 477 55 textmining:470
Rv0213c methyltransferase 653 51 textmining:650
Rv1833c dhmA2 haloalkane dehalogenase 633 50 textmining:630
Rv2529 hyp hypothetical protein 655 49 textmining:653
Rv0325 hyp hypothetical protein 514 47 textmining:511
Rv1767 hyp hypothetical protein 653 46 textmining:652
Rv1829 hyp hypothetical protein 625 46 textmining:624
Rv3365c hyp hypothetical protein 598 45 textmining:597
Rv2527 vapC17 ribonuclease VapC17 513 45 textmining:511
Rv2534c efp elongation factor P 652 44 textmining:651
Rv1766 hyp hypothetical protein 652 44 textmining:651

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: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 4rgu-assembly1_A-2 Crystal Structure of Putative MarR Family Transcriptional Reg (prob 0.95, E=1e-01, TM=0.60)
  • (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_215564.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG4861
  • Curated reference: UniProt P96353 (TrEMBL, unreviewed; 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)
  • Model confidence: ESMFold per-residue pLDDT (mean 88.9, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 26 functional partner(s); context anchor Rv1049
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001124|Rv1048c|
MQASDRTWQSNFIRRWYFTETVEYRPLVKYDASMSWDERTVSALEGAFRSEVRARRVNGPHRDVIVSLDGAEFLVRWLTTGWPRQVAEALHATSRPDILAAPTMSPGARKAAHDAGVGWVDESGAADIHYRNTSTGTTLVIETKGAPPAPLDARIGWRRATLAVCEALLANIAGPTVASVVEATGLSMGSSAQALKFLEKNGHLASATARGPKSARLIVDRDALLDAYAEAADKLRSPISISTGVLWRDPTAGVVKAGQLWDAAGIEWAATSALSASLLAPMQTEIAPMEIYVPGRSWSDLRRAAMAAGLQEIAGGRLILRFFPTPACARLTEQNLQGFRSMLWPRVYADLRTAGVRGEDAAEHLREAMTK