Rv1977 Family assigned · medium auto-curated

H37Rv Rv1977 · MTBC0 mtbc0_002099 · 348 aa · 2243367–2244413 (+) · RefSeq NP_216493.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationM48 family metallopeptidase
Revised (this work)M48 family metallopeptidase. Pfam: Peptidase_M48 (PF01435.25).

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

Curated reference (UniProt)

UniProt O53978 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 O Post-translational modification, protein turnover, chaperones
eggNOG descriptionPeptidase family M48
Orthologous groupCOG0501

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) pseudogene candidate

pN/pS 0.171 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 17.54% of strains (25468) · 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_M48PF01435.25 1.6e-3367–263 Peptidase family M48

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0342 iniA isoniazid inductible protein IniA 664 644 database:643
Rv1978 hyp hypothetical protein 631 526 ctx neighborhood:519
Rv3610c ftsH zinc metalloprotease FtsH 615 484 coexpression:407
Rv0966c hyp hypothetical protein 441 441 ctx cooccurence:439
Rv0351 grpE stress response protein GrpE 492 437 coexpression:418
Rv1286 cysC adenylyl-sulfate kinase 418 418 coexpression:418
Rv0384c clpB chaperone protein ClpB 464 350
Rv3617 ephA epoxide hydrolase EphA 436 176
Rv1979c permease 403 148
Rv2869c rip zinc metalloprotease 507 86 textmining:484
Rv1976c hyp hypothetical protein 557 57 textmining:550
Rv2467 pepN aminopeptidase PepN 562 53 textmining:557
Rv1974 membrane protein 454 52 textmining:448
Rv1975 hyp hypothetical protein 554 50 textmining:550
Rv1993c hyp hypothetical protein 546 50 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: M48 family metallopeptidase
  • Pfam (hmmscan --cut_ga): Peptidase_M48 PF01435.25 (E=2e-33)
  • (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_216493.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M48 (PF01435.25)
  • 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 COG0501
  • Curated reference: UniProt O53978 (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 — 19 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002099|Rv1977|
MSQTPATTRKTFPEISSRAWEHPADRTALSALRRLKGFDQILKLMSGMLRERQHRLLYLASAARVGPRQFADLDALLDECVDVLDASAKPELYVMQSPIADAFTIGMGKPFTVITSGLYDLVTHDEMRFVMGHELGHALSGHAVYRTMMMHLLRLARSFGVLPVGGWALRAIVAALLEWQRKSELSGDRAGLLCAQDLDTALRVEMKLAGGCRLDKLDSEAFLAQAREYETSGDMRDGVLKLLNLELQTHPFSVLRAAALTHWVDTGGYAKVIAGEYPRRADDGNAKFADDLGAAARYYRDGFDQSNDPLIKGIRDGFGGIVEGVGRAASNAADSLGRKITEWRQPSK