Rv0647c Family assigned · medium auto-curated

H37Rv Rv0647c · MTBC0 - · 488 aa · 741151–742617 (-) · RefSeq NP_215161.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains ABC1 (PF03109.23), UbiB_N (PF27536.1) domain(s); putative function inferred from the domain architecture.

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WQI1 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0647c

UniProt still lists this protein as Uncharacterized protein Rv0647c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionunusual protein kinase
Orthologous groupCOG0661
Gene Ontology (13) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, GO:0044424, GO:0044444, GO:0044464 +1 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 1.33 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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
ABC1PF03109.23 2.8e-78132–376 ABC1 atypical kinase-like domain
UbiB_NPF27536.1 2.2e-06400–459 UbiB N-terminal domain

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

Closest characterised functional partner: lipG (lipase/esterase LipG), high confidence from genomic context alone (score 965 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0646c lipG lipase/esterase LipG 996 965 ctx neighborhood:876 coexpression:733 textmining:907
Rv0645c mmaA1 mycolic acid methyltransferase MmaA1 881 667 ctx neighborhood:664 textmining:658
Rv0648 alpha-mannosidase 586 585 ctx neighborhood:558
Rv0649 fabD2 malonyl CoA-acyl carrier protein transacylase 546 546 ctx neighborhood:546
Rv0650 sugar kinase 544 544 ctx neighborhood:544
Rv0644c mmaA2 cyclopropane mycolic acid synthase CmaA 510 425 ctx neighborhood:420
Rv3113 phosphatase 408 408
Rv2232 ptkA protein tyrosine kinase transcriptional regulator PtkA 408 408
Rv1937 oxygenase 436 214
Rv1224 tatB Sec-independent protein translocase protein TatB 497 104 textmining:462
Rv3802c membrane protein 432 46 textmining: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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): ABC1 PF03109.23 (E=3e-78), UbiB_N PF27536.1 (E=2e-06)
  • (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_215161.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ABC1 (PF03109.23), UbiB_N (PF27536.1)
  • 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 COG0661
  • Curated reference: UniProt P9WQI1 (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 — 11 functional partner(s); context anchor lipG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0647c|
MRAEIGPDFRPHYTFGDAYPASERAHVNWELSAPVWHTAQMGSTTHREVAKLDRVPLPVEAARVAATGWQVTRTAVRFIGRLPRKGPWQQKVIKELPQTFADLGPTYVKFGQIIASSPGAFGESLSREFRGLLDRVPPAKTDEVHKLFVEELGDEPARLFASFEEEPFASASIAQVHYATLRSGEEVVVKIQRPGIRRRVAADLQILKRFAQTVELAKLGRRLSAQDVVADFADNLAEELDFRLEAQSMEAWVSHLHASPLGKNIRVPQVHWDFTTERVLTMERVHGIRIDNAAAIRKAGFDGVELVKALLFSVFEGGLRHGLFHGDLHAGNLYVDEAGRIVFFDFGIMGRIDPRTRWLLRELVYALLVKKDHAAAGKIVVLMGAVGTMKPETQAAKDLERFATPLTMQSLGDMSYADIGRQLSALADAYDVKLPRELVLIGKQFLYVERYMKLLAPRWQMMSDPQLTGYFANFMVEVSREHQSDIEV