Rv1215c Family assigned · medium auto-curated

H37Rv Rv1215c · MTBC0 mtbc0_001303 · 561 aa · 1366201–1367886 (-) · RefSeq NP_215731.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationCocE/NonD family hydrolase
Revised (this work)CocE/NonD family hydrolase. Pfam: Peptidase_S15 (PF02129.25), Peptidase_S9 (PF00326.28), PepX_C (PF08530.17).

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

Curated reference (UniProt)

UniProt O05316 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionX-Pro dipeptidyl-peptidase C-terminal non-catalytic domain
Orthologous groupCOG2936
KEGG orthology K06978

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 0.512 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 9 synonymous, 13 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.31% of strains (450) · 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
Peptidase_S15PF02129.25 2.7e-3855–294 X-Pro dipeptidyl-peptidase (S15 family)
Peptidase_S9PF00326.28 5.9e-05122–292 Prolyl oligopeptidase family
PepX_CPF08530.17 5.6e-23339–553 X-Pro dipeptidyl-peptidase C-terminal non-catalytic domain

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

Closest characterised functional partner: Rv1217c (tetronasin ABC transporter integral membrane protein), high confidence from genomic context alone (score 822 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1217c tetronasin ABC transporter integral membrane protein 936 822 ctx neighborhood:821 textmining:658
Rv1216c integral membrane protein 927 746 ctx neighborhood:744 textmining:724
Rv1219c raaS transcriptional regulator 943 726 ctx neighborhood:725 textmining:803
Rv1218c tetronasin ABC transporter ATP-binding protein 900 726 ctx neighborhood:725 textmining:650
Rv2800 hydrolase 690 691 ctx cooccurence:686
Rv1214c PE14 PE family protein PE14 514 496 ctx neighborhood:496
Rv2305 hyp hypothetical protein 473 474 ctx cooccurence:466
Rv1260 oxidoreductase 466 466 ctx cooccurence:460
Rv1220c methyltransferase 863 463 ctx neighborhood:457 textmining:756
Rv1501 hyp hypothetical protein 455 455 ctx cooccurence:455
Rv0399c lpqK lipoprotein LpqK 425 425 ctx cooccurence:406
Rv3161c dioxygenase 421 421 ctx cooccurence:415
Rv3633 hyp hypothetical protein 413 413 ctx cooccurence:407
Rv3510c hyp hypothetical protein 425 192
Rv2938 drrC daunorubicin ABC transporter permease DrrC 610 185 textmining:542

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: CocE/NonD family hydrolase
  • Pfam (hmmscan --cut_ga): Peptidase_S15 PF02129.25 (E=3e-38), Peptidase_S9 PF00326.28 (E=6e-05), PepX_C PF08530.17 (E=6e-23)
  • (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_215731.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S15 (PF02129.25), Peptidase_S9 (PF00326.28), PepX_C (PF08530.17)
  • 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 COG2936
  • Curated reference: UniProt O05316 (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 — 18 functional partner(s); context anchor Rv1217c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001303|Rv1215c|
MARNPSPALDRPWRRPGALRYALERVRGVAKPPITVTDPPADVVIERDVEVPTRDGTLLRINVFRSAEGGARPVIASIHPYGKDALPRRRGNRWTFSPQYRMLRQPKPLTFSALTGWEAPDPAWWTAQGFVVVNADSRGCGRSDGTGDLLSHQEAEDTYDLVGWLADQSWSDGRVVMLGVSYLAISQYAVAALQPPALRAICPWEGFTDAYRDLAFPGGIRESGFTRLWSRGVRRRTRQTYDMEQMQEAHPLRDDFWRSRVPDLSAIKVPMLVCGSFSDNNLHSRGSIRAFTRSGCGHARLYTHRGGKWETFYSATALSEQLKFLRDALAGSSGSRSVRLEVREDRDTITAVREETQWPLAGTRWRPMYLAGPGLLATEPPPTAGSIRFQTRSRAAAFNWTIPEDIELTGPMAARLWVQLDGCDDANLFVGVEKWRDGQFVAFEGSYGWGRDRVTTGWQRVSLRELDPELSQPWEPVPACARPRPVTAGEVVAVDVALGPSATLFRAGEQLRLVVGGRWLSPRNPLTGQFPAAYPRPPRGRVTLHWGPRYDAHLLIPEVPG