Rv0654 Resolved · high auto-curated

H37Rv Rv0654 · MTBC0 mtbc0_000692 · 501 aa · 754086–755591 (+) · RefSeq NP_215168.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)carotenoid cleavage oxygenase
MTBC0 PGAP re-annotationcarotenoid cleavage oxygenase
Revised (this work)Carotenoid cleavage oxygenase. Pfam: RPE65 (PF03055.22).

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

Curated reference (UniProt)

UniProt P9WPR5 SwissProt · reviewed · Evidence at protein level
UniProt nameCarotenoid cleavage oxygenase
EC (curated) EC 1.13.11.-
Curated functionCatalyzes the oxidative cleavage of several carotenoids and apocarotenoids in vitro. In contrast to other carotenoid oxygenases, cleaves substrates at two different sites, namely the central C15-C15' and an excentric double bond at the C13-C14 position, leading to retinal (C20), beta-apo-14'-carotenal (C22) and beta-apo-13-carotenone (C18) from beta-carotene (C40), as well as the corresponding hydroxylated products from zeaxanthin and lutein. Converts beta-apo-10'-carotenal (C27) into beta-apo-13-carotenone (C18) and to minor amounts of beta-apo-15-carotenal (retinal; C20) from the cleavage at.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptiondioxygenase
Orthologous groupCOG3670
KEGG orthology K11159
Gene Ontology (29) GO:0003674, GO:0003824, GO:0006629, GO:0006720, GO:0006721, GO:0008150, GO:0008152, GO:0008300, GO:0009056, GO:0009987, GO:0010436, GO:0016042 +17 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) pseudogene candidate

pN/pS 1.711 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 2.43% of strains (3524) · 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)

PfamAccessioni-EvalueResiduesDescription
RPE65PF03055.22 6.8e-11219–499 Retinal pigment epithelial membrane protein

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

Closest characterised functional partner: Rv0653c (transcriptional regulator), high confidence from genomic context alone (score 785 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0653c transcriptional regulator 785 785 ctx neighborhood:785
Rv0655 mkl ABC transporter ATP-binding protein 771 772 ctx neighborhood:772
Rv1819c bacA vitamin B12 transport ATP-binding protein BacA 619 620 database:563
Rv1389 gmk guanylate kinase 576 577 database:573
Rv0914c lipid carrier protein or keto acyl-CoA thiolase 556 557 ctx cooccurence:543
Rv2213 pepB cytosol aminopeptidase 561 544 database:544
Rv0418 lpqL lipoprotein aminopeptidase LpqL 538 538 database:528
Rv1770 hyp hypothetical protein 538 538 database:528
Rv0178 Mce associated membrane protein 451 430
Rv2390c hyp hypothetical protein 451 430
Rv1362c membrane protein 451 430
Rv1972 Mce associated membrane protein 451 430
Rv1973 Mce associated membrane protein 451 430
Rv1363c membrane protein 451 430
Rv0177 Mce associated protein 451 430

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: carotenoid cleavage oxygenase
  • MTBC0 PGAP product: carotenoid cleavage oxygenase
  • Pfam (hmmscan --cut_ga): RPE65 PF03055.22 (E=7e-112)
  • (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_215168.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RPE65 (PF03055.22)
  • 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 COG3670
  • Curated reference: UniProt P9WPR5 (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 — 30 functional partner(s); context anchor Rv0653c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000692|Rv0654|
MTTAQAAESQNPYLEGFLAPVSTEVTATDLPVTGRIPEHLDGRYLRNGPNPVAEVDPATYHWFTGDAMVHGVALRDGKARWYRNRWVRTPAVCAALGEPISARPHPRTGIIEGGPNTNVLTHAGRTLALVEAGVVNYELTDELDTVGPCDFDGTLHGGYTAHPQRDPHTGELHAVSYSFARGHRVQYSVIGTDGHARRTVDIEVAGSPMMHSFSLTDNYVVIYDLPVTFDPMQVVPASVPRWLQRPARLVIQSVLGRVRIPDPIAALGNRMQGHSDRLPYAWNPSYPARVGVMPREGGNEDVRWFDIEPCYVYHPLNAYSECRNGAEVLVLDVVRYSRMFDRDRRGPGGDSRPSLDRWTINLATGAVTAECRDDRAQEFPRINETLVGGPHRFAYTVGIEGGFLVGAGAALSTPLYKQDCVTGSSTVASLDPDLLIGEMVFVPNPSARAEDDGILMGYGWHRGRDEGQLLLLDAQTLESIATVHLPQRVPMGFHGNWAPTT