Rv2529 Family assigned · medium auto-curated

H37Rv Rv2529 · MTBC0 - · 463 aa · 2852875–2854266 (+) · RefSeq NP_217045.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains ERCC4 (PF02732.22), Lsr2_DNA-bd (PF23359.2) 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 P95024 TrEMBL · unreviewed · Evidence at protein level
UniProt nameERCC4 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionERCC4 domain
Orthologous groupCOG1948

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 0.746 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 8 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.48% of strains (693) · 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
ERCC4PF02732.22 1.9e-14277–399 ERCC4 domain
Lsr2_DNA-bdPF23359.2 4.5e-08427–460 Lsr2 DNA-binding domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3646c topA DNA topoisomerase I 964 953 experimental:883 database:615
Rv1629 polA DNA polymerase I 969 951 experimental:662 database:844 textmining:412
Rv1252c lprE lipoprotein LprE 946 945 experimental:864 database:607
Rv2090 5'-3' exonuclease 891 876 experimental:662 database:622
Rv0641 rplA 50S ribosomal protein L1 843 826 experimental:473 database:683
Rv2737c recA recombinase A 851 806 experimental:528 database:594
Rv2101 helZ helicase HelZ 825 791 experimental:475 database:617
Rv2116 lppK lipoprotein LppK 782 773 experimental:459 database:594
Rv0002 dnaN DNA polymerase III subunit beta 781 772 experimental:459 database:594
Rv1947 hyp hypothetical protein 786 771 database:610
Rv1278 hyp hypothetical protein 769 736 database:615
Rv1277 hyp hypothetical protein 767 730 database:615
Rv1329c dinG ATP-dependent helicase DinG 771 718 database:664
Rv2729c integral membrane protein 714 704 database:516
Rv1179c hyp hypothetical protein 707 687 database:610

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): ERCC4 PF02732.22 (E=2e-14), Lsr2_DNA-bd PF23359.2 (E=4e-08)
  • (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_217045.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ERCC4 (PF02732.22), Lsr2_DNA-bd (PF23359.2)
  • 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 COG1948
  • Curated reference: UniProt P95024 (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 — 114 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2529|
MHLAHRVASSRDTPSSSATPNAVSGSASNAADRPCLVRPPTAPPWAHGPRLRRDPTGGGSTPSIVLSRSTDRSKDGHRIVPAGARKSGVRASTGRLPSTRKTTRSPDCRPSASRTAFGTVTCPFDVTMGSSECLLHRCRTPPVPSHSVELLVAANPAEDSRLPYLIRLPVGAGLVFATSDVWPRTKALYCHRLDIADWPADPVVVDRVELRSCSRRGAAIDVVAARARENRSQLVHTMARGRQVVFWQSPKTRKQSRPGVRTPTARAAGIPELHIVVDAHERYPYTFADKPAKTTREALPCGDYGLKVAGQLVAAVERKALADLTSGVLNGNLKYQLTELAALPRAAVVVEDRYSEIFAHSFARPTAIADGLAELQIGFPNVPIVFCQTRKLAQEYTYRYLAAALTWFVDDADATTVFEPAAAEPEPSSAELRAWAKSVGLPVSDRGRLRPQILQAWRAAHPR