hflX Family assigned · medium auto-curated

H37Rv Rv2725c · MTBC0 - · 495 aa · 3037427–3038914 (-) · RefSeq NP_217241.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)GTP-binding protein HflX
MTBC0 PGAP re-annotation
Revised (this work)GTP-binding protein HflX. Pfam: GTP-bdg_N (PF13167.12), GTP-bdg_M (PF16360.11), MMR_HSR1 (PF01926.30).

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 O33230 TrEMBL · unreviewed · Evidence at protein level
UniProt nameGTPase HflX
Curated functionGTPase that associates with the 50S ribosomal subunit and may have a role during protein synthesis or ribosome biogenesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namehflX
eggNOG descriptionGTPase that associates with the 50S ribosomal subunit and may have a role during protein synthesis or ribosome biogenesis
Orthologous groupCOG2262
KEGG orthology K03665
Gene Ontology (14) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0016462, GO:0016787, GO:0016817, GO:0016818, GO:0016887, GO:0017111 +2 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 0.969 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (169) · 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
GTP-bdg_NPF13167.12 4.1e-3390–177 GTP-binding GTPase N-terminal
GTP-bdg_MPF16360.11 2.4e-28179–265 GTP-binding GTPase Middle Region
MMR_HSR1PF01926.30 6.9e-21273–395 50S ribosome-binding GTPase

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0640 rplK 50S ribosomal protein L11 932 921 experimental:920
Rv2904c rplS 50S ribosomal protein L19 919 916 experimental:911
Rv2442c rplU 50S ribosomal protein L21 915 916 experimental:912
Rv2441c rpmA 50S ribosomal protein L27 916 915 experimental:911
Rv0979A rpmF 50S ribosomal protein L32 921 912 experimental:911
Rv3456c rplQ 50S ribosomal protein L17 912 912 experimental:911
Rv1643 rplT 50S ribosomal protein L20 912 912 experimental:911
Rv0701 rplC 50S ribosomal protein L3 919 908 experimental:905
Rv0702 rplD 50S ribosomal protein L4 919 908 experimental:906
Rv0706 rplV 50S ribosomal protein L22 913 908 experimental:905
Rv3461c rpmJ 50S ribosomal protein L36 907 908 experimental:907
Rv0704 rplB 50S ribosomal protein L2 910 907 experimental:905
Rv0715 rplX 50S ribosomal protein L24 907 907 experimental:905
Rv3443c rplM 50S ribosomal protein L13 915 906 experimental:905
Rv0708 rplP 50S ribosomal protein L16 904 905 experimental:903

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): GTP-binding protein HflX
  • Pfam (hmmscan --cut_ga): GTP-bdg_N PF13167.12 (E=4e-33), GTP-bdg_M PF16360.11 (E=2e-28), MMR_HSR1 PF01926.30 (E=7e-21)
  • (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_217241.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GTP-bdg_N (PF13167.12), GTP-bdg_M (PF16360.11), MMR_HSR1 (PF01926.30)
  • 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 COG2262
  • Curated reference: UniProt O33230 (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 — 87 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2725c|hflX
MPANSDARPAATCHHRVLAMTYPDPPQTGLSDFTPSLGELALEDRSALRRVAGLSTELADVSEVEYRQLRLERVVLVGVWTEGSAADNRASLAELAALAETAGSQVLEGLIQRRDKPDPSTYIGSGKAAELREVIVATGADTVICDGELSPAQLTALEKAVQVKVIDRTALILDIFAQHATSREGKAQVSLAQMEYMLPRLRGWGESMSRQAGGRAGGSGGGVGLRGPGETKIETDRRRIRERMAKLRRDIRAMKQVRDTQRSRRRHSDVPSIAIVGYTNAGKSSLLNALTGAGVLVQDALFATLEPTTRRAEFGDGRPVVLTDTVGFVRHLPTQLVEAFRSTLEEVVHADLLVHVVDGSDGHPLAQIDAVRQVISEVIADHDGDPPPELLVVNKVDVASDLMLAKLRHGLPGAVFVSARTGDGIDALRRRMAELVVPADTAVDVVIPYDRGDLVARVHADGRIQQAEHKPEGTRIKARVPEALAATLREFAPRA