Rv2522c Resolved · high auto-curated

H37Rv Rv2522c · MTBC0 mtbc0_002686 · 470 aa · 2861019–2862431 (-) · RefSeq NP_217038.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationdipeptidase
Revised (this work)Dipeptidase. Pfam: Peptidase_M20 (PF01546.34), M20_dimer (PF07687.20).

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

Curated reference (UniProt)

UniProt I6X4J0 TrEMBL · unreviewed · Evidence at protein level
UniProt namePeptidase M20 dimerisation domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameargE
eggNOG descriptionCOG0624 Acetylornithine deacetylase Succinyl-diaminopimelate desuccinylase and related deacylases
Orthologous groupCOG0624

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 0.307 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 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
Peptidase_M20PF01546.34 9.4e-30102–457 Peptidase family M20/M25/M40
M20_dimerPF07687.20 2.2e-13211–360 Peptidase dimerisation domain

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

Closest characterised functional partner: acpS (holo-ACP synthase), high confidence from genomic context alone (score 832 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2523c acpS holo-ACP synthase 832 832 ctx neighborhood:817
Rv2524c fas fatty acid synthase 569 547 ctx neighborhood:539
Rv1652 argC N-acetyl-gamma-glutamyl-phoshate reductase 544 495 coexpression:401
Rv1658 argG argininosuccinate synthase 519 468
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 492 438 experimental:419
Rv2438c nadE glutamine-dependent NAD(+) synthetase 433 362
Rv1202 dapE succinyl-diaminopimelate desuccinylase DapE 409 45 textmining:407

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: dipeptidase
  • Pfam (hmmscan --cut_ga): Peptidase_M20 PF01546.34 (E=9e-30), M20_dimer PF07687.20 (E=2e-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_217038.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M20 (PF01546.34), M20_dimer (PF07687.20)
  • 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 COG0624
  • Curated reference: UniProt I6X4J0 (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 — 7 functional partner(s); context anchor acpS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002686|Rv2522c|
MSASRRRIASKSGFSCDSASARELVERVREVLPSVRCDLEELVRIESVWADPDRRDEVHRSARAVADLLSQAGFDDVRIVSERGAPAVIARYPAPPGAPTVLLYAHHDVQPEGDRGQWVSPPFEPTERGGRLYGRGTADDKAGIATHVAAFWAHGGRPPVGVTVFVEGEEESGSPSLGRLLAAHRDALAADVIVIADSDNWSTDIPALTVSLRGMADCVVEVATLDHGLHSGLWGGVVPDALTVLVRLLASLHDDDGNVAVAGMHESTAARVDYPAGRVRAESGLLDGVSEIGTGSVPQRLWAKPAITVIGIDTTSVAAASNTLIPRARAKISIRVAPGGDATAHLDAVEAHLRRHAPWGAQVTVTRGEVGQPYAIEASGPVYDAARSAFRQAWGADPIDMGMGGSIPFIAEFAAAFPQATILVTGVEDPGTQAHSVNESLHLGVLERAATAEALLLAKLAAIPTGRAEA