Rv0477 Still unknown · low auto-curated

H37Rv Rv0477 · MTBC0 mtbc0_000502 · 148 aa · 570141–570587 (+) · RefSeq NP_214991.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2599 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF2599. Function unknown. Foldseek best (non-significant) hit: 3tgo-assembly2_D Crystal structure of the E. coli BamCD complex (prob 0.01, TM 0.15).

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

Curated reference (UniProt)

UniProt P9WKV9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0477

UniProt still lists this protein as Uncharacterized protein Rv0477; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2599)
Orthologous group2EB1C
Gene Ontology (2) GO:0005575, GO:0005576

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 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
DUF2599PF10783.15 1.5e-4146–142 Protein of unknown function (DUF2599)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 92.5 (very high). 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
3tgo-assembly2_D 0.01 0.15 7.0e+00 3tgo-assembly2_D Crystal structure of the E. coli BamCD complex

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

Closest characterised functional partner: deoC (2-deoxyribose-5-phosphate aldolase), high confidence from genomic context alone (score 883 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0478 deoC 2-deoxyribose-5-phosphate aldolase 883 883 ctx neighborhood:882
Rv0476 transmembrane protein 882 882 ctx neighborhood:882
Rv0475 hbhA heparin binding hemagglutinin HbhA 835 829 ctx neighborhood:766
Rv0474 HTH-type transcriptional regulator 671 668 ctx neighborhood:661
Rv3724B cut5b Rv3724B, (MTV025.072), len: 187 aa. Probable cut5b,truncated cutinase, similar to C-terminal end of others e.g. Q9XB09|RVD2-RV1758 protein ( 592 592 ctx cooccurence:587
Rv0283 eccB3 ESX-3 secretion system protein EccB3 583 583 ctx cooccurence:511
Rv1758 cut1 cutinase 545 546 ctx cooccurence:540
Rv1364c sigma factor regulatory protein 520 515 coexpression:500
Rv3035 hyp hypothetical protein 510 510 ctx cooccurence:507
Rv2923c hyp hypothetical protein 489 490 ctx cooccurence:483
Rv2942 mmpL7 transmembrane transport protein MmpL7 481 481 ctx cooccurence:481
Rv2429 ahpD alkyl hydroperoxide reductase AphD 471 471 ctx cooccurence:471
Rv0676c mmpL5 transmembrane transport protein MmpL5 470 470 ctx cooccurence:470
Rv1874 hyp hypothetical protein 459 459 ctx cooccurence:459
Rv2608 PPE42 PPE family protein PPE42 456 456 ctx cooccurence:456

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: DUF2599 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF2599 PF10783.15 (E=1e-41)
  • Foldseek best: 3tgo-assembly2_D Crystal structure of the E. coli BamCD complex (prob 0.01, E=7e+00, TM=0.15)
  • (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_214991.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2599 (PF10783.15)
  • 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 2EB1C
  • Curated reference: UniProt P9WKV9 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 92.5, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 29 functional partner(s); context anchor deoC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000502|Rv0477|
MKALVAVSAVAVVALLGVSSAQADPEADPGAGEANYGGPPSSPRLVDHTEWAQWGSLPSLRVYPSQVGRTASRRLGMAAADAAWAEVLALSPEADTAGMRAQFICHWQYAEIRQPGKPSWNLEPWRPVVDDSEMLASGCNPGSPEESF