Rv3551 Family assigned · medium auto-curated

H37Rv Rv3551 · MTBC0 mtbc0_003768 · 292 aa · 4013573–4014451 (+) · RefSeq NP_218068.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)CoA-transferase subunit alpha
MTBC0 PGAP re-annotationCoA transferase subunit A
Revised (this work)CoA transferase subunit A. Pfam: CoA_trans (PF01144.30).

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

Curated reference (UniProt)

UniProt P9WPW1 SwissProt · reviewed · Evidence at protein level
UniProt nameCholesterol ring-cleaving hydrolase IpdA subunit
EC (curated) EC 4.1.99.-
Curated functionInvolved in the final steps of cholesterol and steroid degradation. Opens the last steroid ring of cholesterol by catalyzing the hydrolysis of (3E)-2-(2-carboxylatoethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA (COCHEA-CoA) to 6-methyl-3,7-dioxodecanedioyl-CoA (MeDODA-CoA).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionAcyl CoA acetate 3-ketoacid CoA transferase, alpha subunit
Orthologous groupCOG1788
EC number EC 2.8.3.12
KEGG orthology K01039
KEGG pathways map00643, map00650, map01120
Gene Ontology (8) GO:0008150, GO:0040007, GO:0044110, GO:0044116, GO:0044117, GO:0044403, GO:0044419, GO:0051704

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 0.256 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 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
CoA_transPF01144.30 2.9e-456–233 Coenzyme A transferase

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

Closest characterised functional partner: Rv3552 (CoA-transferase subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3552 CoA-transferase subunit beta 999 1000 ctx neighborhood:882 cooccurence:774 coexpression:952 experimental:999 database:900 textmining:820
Rv3550 echA20 enoyl-CoA hydratase EchA20 999 998 ctx neighborhood:882 cooccurence:746 coexpression:869 database:500 textmining:634
Rv3553 oxidoreductase 996 981 ctx neighborhood:773 cooccurence:454 coexpression:860 textmining:803
Rv3549c short-chain type dehydrogenase/reductase 983 981 ctx neighborhood:787 cooccurence:584 coexpression:806
Rv3548c short-chain type dehydrogenase/reductase 963 947 ctx neighborhood:588 cooccurence:486 coexpression:770
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 969 938 ctx cooccurence:682 coexpression:810 textmining:529
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 937 931 coexpression:670 experimental:766
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 931 929 ctx cooccurence:730 coexpression:742
Rv3559c oxidoreductase 955 919 ctx cooccurence:706 coexpression:730 textmining:479
Rv3375 amiD amidase 901 901 database:900
Rv1263 amiB2 amidase AmiB 900 901 database:900
Rv2888c amiC amidase AmiC 900 901 database:900
Rv3175 amidase 900 900 database:900
Rv2363 amiA2 amidase 900 900 database:900
Rv3561 fadD3 fatty-acid--CoA ligase FadD3 894 860 coexpression:811

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: CoA-transferase subunit alpha
  • MTBC0 PGAP product: CoA transferase subunit A
  • Pfam (hmmscan --cut_ga): CoA_trans PF01144.30 (E=3e-45)
  • (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_218068.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CoA_trans (PF01144.30)
  • 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 COG1788
  • Curated reference: UniProt P9WPW1 (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 — 68 functional partner(s); context anchor Rv3552
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003768|Rv3551|
MPDKRTSLDDAVAQLRSGMTIGIAGWGSRRKPMAFVRAILRSDVTDLTVVTYGGPDLGLLCSAGKVKRVYYGFVSLDSPPFYDPWFAHARTSGAIEAREMDEGMLRCGLQAAAQRLPFLPIRAGLGSSVPQFWAGELQTVTSPYPAPGGGYETLIAMPALRLDAAFAHLNLGDSHGNAAYTGIDPYFDDLFLMAAERRFLSVERIVATEELVKSVPPQALLVNRMMVDAIVEAPGGAHFTTAAPDYGRDEQFQRHYAEAASTQVGWQQFVHTYLSGTEADYQAAVHNFGASR