Rv3434c Family assigned · medium auto-curated

H37Rv Rv3434c · MTBC0 mtbc0_003653 · 237 aa · 3879101–3879814 (-) · RefSeq NP_217951.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationrhomboid-like protein
Revised (this work)Rhomboid-like protein. Pfam: Rhomboid_2 (PF20401.4).

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

Curated reference (UniProt)

UniProt I6YC44 TrEMBL · unreviewed · Predicted
UniProt namePossible conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2CJZS

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) pseudogene candidate

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 5 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 2.29% of strains (3325) · 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
Rhomboid_2PF20401.4 4.9e-6520–214 Rhomboid-like protein

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

Closest characterised functional partner: Rv3435c (transmembrane protein), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3435c transmembrane protein 903 884 ctx neighborhood:832
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 945 883 ctx neighborhood:882 textmining:550
Rv3432c gadB glutamate decarboxylase GadB 830 831 ctx neighborhood:829
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 895 732 ctx neighborhood:730 textmining:625
Rv0180c transmembrane protein 706 707 ctx cooccurence:705
Rv2423 hyp hypothetical protein 669 669 ctx cooccurence:669
Rv3166c hyp hypothetical protein 664 664 ctx cooccurence:662
Rv2638 hyp hypothetical protein 652 653 ctx cooccurence:650
Rv2729c integral membrane protein 624 624 ctx cooccurence:624
Rv3899c hyp hypothetical protein 599 599 ctx cooccurence:597
Rv2963 integral membrane protein 568 568 ctx cooccurence:568
Rv0090 membrane protein 535 535 ctx cooccurence:535
Rv2042c hyp hypothetical protein 525 526 ctx cooccurence:515
Rv1635c mannosyltransferase 517 518 ctx cooccurence:516
Rv2777c hyp hypothetical protein 499 499 ctx cooccurence:478

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: rhomboid-like protein
  • Pfam (hmmscan --cut_ga): Rhomboid_2 PF20401.4 (E=5e-65)
  • (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_217951.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rhomboid_2 (PF20401.4)
  • 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 2CJZS
  • Curated reference: UniProt I6YC44 (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 — 54 functional partner(s); context anchor Rv3435c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003653|Rv3434c|
MADASVVARLRSWALAVWHFVSNAPLTYAWLVVLVITTIIQNNLTGSQLHFVLLHRSTNIAELGRDPLEVLFSSLLWIDGRNLEPYLLLFTLFLAPAEHWLGHLRWLTVGLTAHIGATYLSEGLLYLAIQHRDASERMVHARDIGVSYFLVGVMAVLTYHIAKPWRWGYLGVLLVIFGFPLIAMDKAELDFTAVGHFASILIGLLFYPMARERDGRLWNPARIKSLLHRRGTRGRRA