greA Resolved · high auto-curated

H37Rv Rv1080c · MTBC0 - · 164 aa · 1205304–1205798 (-) · RefSeq NP_215596.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcription elongation factor GreA
MTBC0 PGAP re-annotation
Revised (this work)Transcription elongation factor GreA. Pfam: GreA_GreB_N (PF03449.21), GreA_GreB (PF01272.26).

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 P9WMT9 SwissProt · reviewed · Evidence at protein level
UniProt nameTranscription elongation factor GreA
Curated functionNecessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by cleavage factors such as GreA or GreB allows the resumption of elongation from the new 3'terminus. GreA releases sequences of 2 to 3 nucleotides.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namegreA
eggNOG descriptionNecessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by cleavage factors such as GreA or GreB allows the resumption of elongation from the new 3'terminus. GreA releases sequences of 2 to 3 nucleotides
Orthologous groupCOG0782
KEGG orthology K03624
Gene Ontology (17) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0042221, GO:0044424 +5 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 0.313 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 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
GreA_GreB_NPF03449.21 2.6e-258–76 Transcription elongation factor, N-terminal
GreA_GreBPF01272.26 8.1e-1382–160 Transcription elongation factor, GreA/GreB, C-term

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

Closest characterised functional partner: Rv1081c (membrane protein), medium confidence from genomic context alone (score 563 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 943 922 coexpression:472 experimental:819
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 882 866 experimental:798
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 915 862 experimental:818 textmining:414
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 862 844 experimental:793
Rv2785c rpsO 30S ribosomal protein S15 565 565 coexpression:560
Rv1081c membrane protein 562 563 ctx neighborhood:560
Rv3458c rpsD 30S ribosomal protein S4 573 554 coexpression:466
Rv0702 rplD 50S ribosomal protein L4 564 554 coexpression:460
Rv1082 mca mycothiol S-conjugate amidase 543 543 ctx neighborhood:468
Rv2904c rplS 50S ribosomal protein L19 571 531 coexpression:515
Rv2783c gpsI bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase 550 496 coexpression:479
Rv1298 rpmE 50S ribosomal protein L31 499 480 coexpression:477
Rv0704 rplB 50S ribosomal protein L2 476 476 coexpression:475
Rv1083 hyp hypothetical protein 453 454 ctx neighborhood:452
Rv0639 nusG transcription termination/antitermination protein NusG 746 440 textmining:565

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): transcription elongation factor GreA
  • Pfam (hmmscan --cut_ga): GreA_GreB_N PF03449.21 (E=3e-25), GreA_GreB PF01272.26 (E=8e-13)
  • (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_215596.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GreA_GreB_N (PF03449.21), GreA_GreB (PF01272.26)
  • 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 COG0782
  • Curated reference: UniProt P9WMT9 (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 — 45 functional partner(s); context anchor Rv1081c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1080c|greA
MTDTQVTWLTQESHDRLKAELDQLIANRPVIAAEINDRREEGDLRENGGYHAAREEQGQQEARIRQLQDLLSNAKVGEAPKQSGVALPGSVVKVYYNGDKSDSETFLIATRQEGVSDGKLEVYSPNSPLGGALIDAKVGETRSYTVPNGSTVSVTLVSAEPYHS