Rv3555c Family assigned · medium auto-curated

H37Rv Rv3555c · MTBC0 mtbc0_003772 · 289 aa · 4018507–4019376 (-) · RefSeq NP_218072.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF559 domain-containing protein
Revised (this work)DUF559 domain-containing protein. Pfam: AbiEi_1 (PF09407.17), DUF559 (PF04480.19).

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

Curated reference (UniProt)

UniProt P96837 TrEMBL · unreviewed · Predicted
UniProt nameConserved protein

UniProt still lists this protein as Conserved 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 groupCOG2852

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 2.182 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 6 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
AbiEi_1PF09407.17 7.7e-0663–174 AbiEi antitoxin C-terminal domain
DUF559PF04480.19 2.6e-04217–271 Protein of unknown function (DUF559)

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

Closest characterised functional partner: fadA6 (acetyl-CoA acetyltransferase FadA), medium confidence from genomic context alone (score 597 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3297 nei endonuclease VIII 820 820 coexpression:817
Rv3296 lhr ATP-dependent helicase 800 800 coexpression:799
Rv3202c adnA ATP-dependent DNA helicase 744 745 coexpression:730
Rv2191 hyp hypothetical protein 730 731 coexpression:730
Rv3556c fadA6 acetyl-CoA acetyltransferase FadA 597 597 ctx neighborhood:580
Rv0804 hyp hypothetical protein 558 558 ctx cooccurence:558
Rv3859c gltB glutamate synthase large subunit 522 522 coexpression:515
Rv3586 disA DNA integrity scanning protein DisA 512 512 coexpression:441
Rv3557c kstR2 HTH-type transcriptional regulator KstR2 485 485 ctx neighborhood:480
Rv2735c hyp hypothetical protein 483 484 coexpression:409
Rv2345 transmembrane protein 481 481 ctx cooccurence:481
Rv0767c HTH-type transcriptional regulator 437 437 ctx cooccurence:437
Rv3585 radA DNA repair protein RadA 432 432 coexpression:431
Rv0083 oxidoreductase 807 63 textmining:803

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: DUF559 domain-containing protein
  • Pfam (hmmscan --cut_ga): AbiEi_1 PF09407.17 (E=8e-06), DUF559 PF04480.19 (E=3e-04)
  • (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_218072.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AbiEi_1 (PF09407.17), DUF559 (PF04480.19)
  • 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 COG2852
  • Curated reference: UniProt P96837 (TrEMBL, unreviewed; Predicted)
  • 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 — 14 functional partner(s); context anchor fadA6
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003772|Rv3555c|
MDELPWPVLGSEVLAAKAIPERAMRQLYEPVYPGVYAPAGVELTARQRAHAAWLWSRRRAVVAGNSAAALLGAKWVNPALDAELVHANRKPPPRIVVHTDRLAPHETVAVDGVAVTTPARTAFDIGRRTPSRLQAVQRLDALANSTDVKVADVQAVIAEHTGARGLVRLRAVLPLIDGGAESPQETWTRLVLIDAGLPKPQTQIRVFDDYGDFVARIDLGYEQLRVGVEYDGPQHWTDPAQRARDIERSTALLDLGWTIIRVTSELLRYRRGTFVGRVDAAMRAAGWRP