Rv3770c Family assigned · low

H37Rv Rv3770c · MTBC0 mtbc0_003994 · 191 aa · 4239321–4239896 (-) · RefSeq NP_218287.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Polytopic integral membrane protein with 5 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined.

Curated reference (UniProt)

UniProt P72037 TrEMBL · unreviewed · Predicted
UniProt nameHypothetical leucine rich protein

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 1.292 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.75% of strains (1089) · 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)

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

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

Closest characterised functional partner: Rv3770A (Rv3770A, len: 60 aa. Probable remnant of a transposase, similar to many e.g. Rv2812|MTCY16B7.31c|Z81331_17 IS1604 putative transposase from ), medium confidence from genomic context alone (score 556 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3770A Rv3770A, len: 60 aa. Probable remnant of a transposase, similar to many e.g. Rv2812|MTCY16B7.31c|Z81331_17 IS1604 putative transposase from 557 556 ctx neighborhood:536
Rv3770B Rv3770B, len: 63 aa. Probable remnant of a transposase, similar to many e.g. Rv2812|MTCY16B7.31c|Z81331_17 IS1604 putative transposase from 528 528 ctx neighborhood:521

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

  • DeepTMHMM: 5 transmembrane helices (type TM)
  • Integral membrane topology (localisation feature, not a function)
  • DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.

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_218287.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt P72037 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 88.3, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 2 functional partner(s); context anchor Rv3770A
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003994|Rv3770c|
MLSGIQQNTLMDNDPLAHGYYVADLLVALAVVVLMLRARRTRPELARMLLLGTLIGLVWELPVFGLSAWTNTPIIEWATPLPLPTVVFLLAHSVWDGALLTMGWLLARALTGEPAGALGLTVQVLWGQLTALAVELSAILAGTWSYVDDLWFNPVMFWFRGHPVTAAMQLTWLLAPLCFAALVRRLALTAR