Rv2314c Family assigned · medium auto-curated

H37Rv Rv2314c · MTBC0 mtbc0_002462 · 457 aa · 2610666–2612039 (-) · RefSeq NP_216830.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationTldD/PmbA family protein
Revised (this work)TldD/PmbA family protein. Pfam: PmbA_TldD_3rd (PF19289.5).

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

Curated reference (UniProt)

UniProt P71898 TrEMBL · unreviewed · Evidence at protein level
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 descriptionPutative modulator of DNA gyrase
Orthologous groupCOG0312

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 0.18 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 3 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
PmbA_TldD_3rdPF19289.5 1.4e-26221–451 PmbA/TldA metallopeptidase C-terminal domain

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

Closest characterised functional partner: uspA (sugar ABC transporter permease UspA), high confidence from genomic context alone (score 791 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2315c hyp hypothetical protein 973 974 ctx neighborhood:882 cooccurence:774
Rv2313c hyp hypothetical protein 879 880 ctx neighborhood:879
Rv2316 uspA sugar ABC transporter permease UspA 790 791 ctx neighborhood:790
Rv2317 uspB sugar ABC transporter permease UspB 789 790 ctx neighborhood:790
Rv2318 uspC sugar ABC transporter substrate-binding lipoprotein UspC 789 790 ctx neighborhood:790
Rv1473A transcriptional regulator 606 606 ctx cooccurence:606
Rv0090 membrane protein 531 531 ctx cooccurence:531
Rv3118 sseC1 hyp hypothetical protein 442 443 ctx cooccurence:439
Rv0814c sseC2 hyp hypothetical protein 440 441 ctx cooccurence:439
Rv2525c hyp hypothetical protein 416 417 ctx cooccurence:413
Rv1094 desA2 acyl-ACP desaturase DesA 408 380
Rv0824c desA1 acyl-ACP desaturase DesA 404 376

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: TldD/PmbA family protein
  • Pfam (hmmscan --cut_ga): PmbA_TldD_3rd PF19289.5 (E=1e-26)
  • (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_216830.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PmbA_TldD_3rd (PF19289.5)
  • 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 COG0312
  • Curated reference: UniProt P71898 (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 — 12 functional partner(s); context anchor uspA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002462|Rv2314c|
MIEPQHAVNIVLKEAARSGRADETMVLVTEKVEATLRWAGNSMTTNGVSHSRNVTVISIVRRGDSAFVGSVVSAEVDPSVLPGLVVSSQDAARSAPEAGDAAPLLADTGEPDDWDAPVPGTGAGVFTGIAGSLSRGFRGADRLYGYAHRSVSTTFLASSTGLRRRYTQPTGAIEINAKRGDASAWVGIGTPDFVEVPIDLMLERLSTRLRWAQRTVELPAGRYQTIMPPSTVADMMIYLGWSMAGRGAQEGRTAFSAPGGGTRVGERLTELPLTLFTDPAAPGLACTPFVAVSNSSETQSVFDNGMEISQVDWIRSGVINALAYPRATAAKFDAPVAVAADNLIMTGGSADLADMIAGTERGLLLTTLWYIREVDPTTLLLTGLTRDGVYLVEDGEVSAAVNNFRFNESPLDLLRRATEAGVSEPTLPREWSDWVTRTAMPPLRIPDFHMSSVSQAQ