Rv3669 Family assigned · medium auto-curated

H37Rv Rv3669 · MTBC0 mtbc0_003888 · 172 aa · 4134657–4135175 (+) · RefSeq NP_218186.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationphage holin family protein
Revised (this work)Phage holin family protein. Pfam: Phage_holin_3_6 (PF07332.17).

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

Curated reference (UniProt)

UniProt O69637 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPutative Actinobacterial Holin-X, holin superfamily III
Orthologous group2DPPE

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 0.355 · 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
Phage_holin_3_6PF07332.17 4.6e-3232–145 Putative Actinobacterial Holin-X, holin superfamily III

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

Closest characterised functional partner: ephE (epoxide hydrolase EphE), high confidence from genomic context alone (score 900 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3670 ephE epoxide hydrolase EphE 900 900 ctx neighborhood:881
Rv3668c protease 733 733 ctx neighborhood:693
Rv3207c hyp hypothetical protein 691 691 ctx cooccurence:691
Rv1417 membrane protein 655 655 ctx cooccurence:655
Rv0862c hyp hypothetical protein 596 596 ctx cooccurence:596
Rv3311 hyp hypothetical protein 595 595 ctx cooccurence:589
Rv3259 hyp hypothetical protein 567 568 ctx cooccurence:546
Rv2049c hyp hypothetical protein 564 565 ctx cooccurence:562
Rv2170 GCN5-like N-acetyltransferase 562 563 ctx cooccurence:561
Rv3438 hyp hypothetical protein 551 551 ctx cooccurence:548
Rv3256c hyp hypothetical protein 545 545 ctx cooccurence:545
Rv3662c hyp hypothetical protein 539 539 ctx cooccurence:426
Rv3212 hyp hypothetical protein 538 521 ctx cooccurence:519
Rv1698 mctB copper transporter MctB 514 515 ctx cooccurence:512
Rv0556 transmembrane protein 505 506 ctx cooccurence:503

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: transmembrane protein
  • MTBC0 PGAP product: phage holin family protein
  • Pfam (hmmscan --cut_ga): Phage_holin_3_6 PF07332.17 (E=5e-32)
  • (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_218186.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Phage_holin_3_6 (PF07332.17)
  • 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 2DPPE
  • Curated reference: UniProt O69637 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 39 functional partner(s); context anchor ephE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003888|Rv3669|
MSKIDRKNGVPSTLTTIPLADPHAGPAEPSIGDLIKDATTQMSTLVRAEVELARAEITRDVKKGLTGSVFFISSLVVGFYSTFFFFFFVAELLDTWIWRWVAFLLVFAIMVVVTAVLALLGFLKVRRIRGPRQTIASVKETRTALTPGHDKTPVTPKPVTSDRATPVDPSGW