Rv2953 Resolved · high auto-curated

H37Rv Rv2953 · MTBC0 mtbc0_003135 · 418 aa · 3326454–3327710 (+) · RefSeq NP_217469.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)trans-acting enoyl reductase
MTBC0 PGAP re-annotationtrans-acting enoyl reductase
Revised (this work)Trans-acting enoyl reductase. Pfam: Sacchrp_dh_NADP (PF03435.25).

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

Curated reference (UniProt)

UniProt P9WGV5 SwissProt · reviewed · Evidence at protein level
UniProt nameTrans-acting enoyl reductase
EC (curated) EC 1.3.1.-
Curated functionInvolved in the reduction of the double bond between C-4 and C-5 during phthiocerol dimycocerosates (DIM A) and glycosylated phenolphthiocerol dimycocerosates (PGL) biosynthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameLYS1
eggNOG descriptionInvolved in the reduction of the double bond between C-4 and C-5 during phthiocerol dimycocerosates (DIM A) and glycosylated phenolphthiocerol dimycocerosates (PGL) biosynthesis
Orthologous groupCOG3268
KEGG orthology K12445
Gene Ontology (36) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006629, GO:0006643, GO:0006664, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009247 +24 more

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 0.364 · 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
Sacchrp_dh_NADPPF03435.25 8.2e-0810–135 Saccharopine dehydrogenase NADP binding domain

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

Closest characterised functional partner: Rv2952 (phthiotriol/phenolphthiotriol dimycocerosates methyltransferase), high confidence from genomic context alone (score 923 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2952 phthiotriol/phenolphthiotriol dimycocerosates methyltransferase 945 923 ctx neighborhood:724 coexpression:733
Rv2951c phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase 963 730 ctx neighborhood:469 database:500 textmining:870
Rv0241c htdX 3-hydroxyacyl-thioester dehydratase HtdX 409 408
Rv3854c ethA monooxygenase EthA 544 303
Rv0632c echA3 enoyl-CoA hydratase EchA3 406 224
Rv1254 acyltransferase 530 81 textmining:510
Rv1484 inhA NADH-dependent enoyl-[ACP 795 57 textmining:792
Rv1679 fadE16 acyl-CoA dehydrogenase FadE16 444 54 textmining:437
Rv2960c hyp hypothetical protein 630 46 textmining:629
Rv2956 hyp hypothetical protein 513 46 textmining:511
Rv3060c GntR family transcriptional regulator 511 41 textmining:511
Rv0854 hyp hypothetical protein 443 41 textmining:443
Rv2382c mbtC polyketide synthetase 414 41 textmining:414
Rv2961 transposase 403 41 textmining:403

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: trans-acting enoyl reductase
  • MTBC0 PGAP product: trans-acting enoyl reductase
  • Pfam (hmmscan --cut_ga): Sacchrp_dh_NADP PF03435.25 (E=8e-08)
  • (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_217469.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sacchrp_dh_NADP (PF03435.25)
  • 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 COG3268
  • Curated reference: UniProt P9WGV5 (SwissProt, reviewed; 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 — 14 functional partner(s); context anchor Rv2952
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003135|Rv2953|
MSPAEREFDIVLYGATGFSGKLTAEHLAHSGSTARIALAGRSSERLRGVRMMLGPNAADWPLILADASQPLTLEAMAARAQVVLTTVGPYTRYGLPLVAACAKAGTDYADLTGELMFCRNSIDLYHKQAADTGARIILACGFDSIPSDLNVYQLYRRSVEDGTGELCDTDLVLRSFSQRWVSGGSVATYSEAMRTASSDPEARRLVTDPYTLTTDRGAEPELGAQPDFLRRPGRDLAPELAGFWTGGFVQAPFNTRIVRRSNALQEWAYGRRFRYSETMSLGKSMAAPILAAAVTGTVAGTIGLGNKYFDRLPRRLVERVTPKPGTGPSRKTQERGHYTFETYTTTTTGARYRATFAHNVDAYKSTAVLLAQSGLALALDRDRLAELRGVLTPAAAMGDALLARLPGAGVVMGTTRLS