Rv2264c Family assigned · medium auto-curated

H37Rv Rv2264c · MTBC0 mtbc0_002406 · 592 aa · 2562677–2564455 (-) · RefSeq NP_216780.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationHsp70 family protein
Revised (this work)Hsp70 family protein. Pfam: HSP70 (PF00012.27).

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

Curated reference (UniProt)

UniProt O53538 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved hypothetical proline rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionMolecular chaperone
Orthologous groupCOG0443

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 0.394 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 6 missense, 0 nonsense, 8 frameshift
Disruption 8 distinct premature-stop/frameshift site(s); most common in 23.96% of strains (34798) · convergent

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
HSP70PF00012.27 1.6e-17150–364 Hsp70 protein

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

Closest characterised functional partner: iniA (isoniazid inductible protein IniA), high confidence from genomic context alone (score 786 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2299c htpG chaperone protein HtpG 977 969 coexpression:668 experimental:772 database:622
Rv0351 grpE stress response protein GrpE 961 947 coexpression:703 experimental:773
Rv2373c dnaJ2 chaperone protein DnaJ 942 934 coexpression:630 experimental:476 database:601
Rv0352 dnaJ1 chaperone protein DnaJ 939 929 coexpression:628 experimental:476 database:601
Rv3417c groEL1 chaperonin GroEL 853 829 coexpression:629 experimental:410
Rv0440 groEL2 molecular chaperone GroEL 850 826 coexpression:629 experimental:410
Rv0384c clpB chaperone protein ClpB 833 809 coexpression:616 experimental:508
Rv2667 clpC2 ATP-dependent protease ATP-binding subunit ClpC 833 809 coexpression:615 experimental:508
Rv3596c clpC1 ATP-dependent protease ATP-binding subunit ClpC 832 808 coexpression:614 experimental:508
Rv0342 iniA isoniazid inductible protein IniA 798 786 ctx cooccurence:587 database:411
Rv3529c hyp hypothetical protein 783 772 experimental:455 database:567
Rv2267c stf3 hyp hypothetical protein 782 770 experimental:455 database:567
Rv1691 hyp hypothetical protein 781 769 experimental:455 database:567
Rv0708 rplP 50S ribosomal protein L16 780 760 experimental:749
Rv3418c groES chaperonin GroES 824 759 coexpression:671

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: hypothetical protein
  • MTBC0 PGAP product: Hsp70 family protein
  • Pfam (hmmscan --cut_ga): HSP70 PF00012.27 (E=2e-17)
  • (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_216780.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HSP70 (PF00012.27)
  • 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 COG0443
  • Curated reference: UniProt O53538 (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 — 175 functional partner(s); context anchor iniA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002406|Rv2264c|
MATGARPALGLSIGVTNLAAVAADHSITRKPVLTLYRQRPPEVGVPSENPRLDEPGLVITDFVDRVGDSVGIVAADGSVYRSEALVADALLALAYTATGGRALPGSVTVTYPAHWGPAAVAALDSALRRASEWSHGTSSTAQPLSLLPDAAAALYAIRADPGIPARGIVAVCDFGGSGTGITLVDAADEYRPVAATVRHQAFSGDLIDQSLLSYVMSELPGTGAFDPAGTSAIGSLTKLRIECRKAKERLSSSTVTTLTDALGGDIRLTRNELEDTIRDSLDSVGRALEQTLARSGIRTAELVAIVSVGGGANIPAVTTTLSGRFCVPVVRTPRPQLTAAFGGALWAARRPGDTSATVLTAVTSATATAPADAPASVLQPALAWSEADEDSHIGPAPGYTAARPSLSFDHDAHAEPEPKSPPIPWYRLPAVIITGTTVAVLLVGAAVAIGLSTGDQPTAPGTPQRPGVTTTAAPPPSPAPASDGPTTEPAPPVQAPATGGPAPPLQQPLPPPPTTTNTQPAVTTDVITPAPTTPASAPPATTQPPATTQPPATTSPSPPPIPPIPPIPEIPQLPPGIPQVPGIGQFSAISGS