Rv3075c Resolved · high auto-curated

H37Rv Rv3075c · MTBC0 mtbc0_003269 · 307 aa · 3459414–3460337 (-) · RefSeq NP_217591.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationCoA ester lyase
Revised (this work)CoA ester lyase. Pfam: HpcH_HpaI (PF03328.21).

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

Curated reference (UniProt)

UniProt I6YF40 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 G Carbohydrate transport and metabolism
Preferred namecitE_2
eggNOG descriptionBelongs to the HpcH HpaI aldolase family
Orthologous groupCOG2301
EC number EC 4.1.3.34
KEGG orthology K01644
KEGG pathways map02020

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 0.664 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
HpcH_HpaIPF03328.21 5.0e-2627–228 HpcH/HpaI aldolase/citrate lyase

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

Closest characterised functional partner: hab (hydroxylaminobenzene mutase), 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)
Rv2498c citE citrate (pro-3S)-lyase subunit beta 949 926 database:900
Rv0727c fucA L-fuculose phosphate aldolase FucA 730 730 coexpression:730
Rv3076 hyp hypothetical protein 602 602 ctx neighborhood:602
Rv3078 hab hydroxylaminobenzene mutase 597 597 ctx neighborhood:596
Rv2286c hyp hypothetical protein 549 549 ctx neighborhood:544
Rv3073c hyp hypothetical protein 545 545 ctx neighborhood:544
Rv3077 hydrolase 545 545 ctx neighborhood:545
Rv2499c oxidase regulatory-like protein 504 481
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 455 448
Rv2332 mez malate oxidoreductase 467 440 coexpression:408
Rv2753c dapA 4-hydroxy-tetrahydrodipicolinate synthase 408 409 coexpression:408
Rv1493 mutB methylmalonyl-CoA mutase large subunit 409 185
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 532 85 textmining:511
Rv0772 purD phosphoribosylamine--glycine ligase 607 68 textmining:596
Rv1480 hyp hypothetical protein 623 50 textmining:620

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: CoA ester lyase
  • Pfam (hmmscan --cut_ga): HpcH_HpaI PF03328.21 (E=5e-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_217591.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HpcH_HpaI (PF03328.21)
  • 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 COG2301
  • Curated reference: UniProt I6YF40 (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 — 17 functional partner(s); context anchor hab
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003269|Rv3075c|
MTSMYEQVDTNTADPVAGSRIDPVLARSWLLVNGAHGDRFESAAHSRADIVVLDIEDAVAPKDKHAARDNAVRWFGDGNADWVRINGFGTPWWADDLAMLADSPVGGVMLAMVESVDHVTETAKRLPNVPIVALVETARGLERINEIAAAKGTFRLAFGIGDFRRDTGFGEDPATLAYARSRFTIAARAAGLPSAIDGPTIGSNALKLIEATAVSAEFGMTGKICLSPDQCPVVNEGLSPSQDEIVWAKEFFAEFARDGGEIRNGSDLPRIARATKILDLARAYGIEVSDFEDEPVHMPAPTDTYHY