Rv1770 Family assigned · medium auto-curated

H37Rv Rv1770 · MTBC0 - · 428 aa · 2003878–2005164 (+) · RefSeq NP_216286.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Peptidase_M28 (PF04389.23) 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 O06803 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 descriptionPeptidase family M28
Orthologous groupCOG2234

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 0.358 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (378) · 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_M28PF04389.23 1.3e-12252–418 Peptidase family M28

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

Closest characterised functional partner: Rv1771 (L-gulono-1,4-lactone dehydrogenase), high confidence from genomic context alone (score 888 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1769 hyp hypothetical protein 970 971 ctx neighborhood:881 coexpression:734
Rv1771 L-gulono-1,4-lactone dehydrogenase 887 888 ctx neighborhood:881
Rv2045c lipT carboxylesterase LipT 715 700 database:587
Rv1104 Rv1104, (MTV017.57), len: 229 aa. Possible para-nitrobenzyl esterase (fragment; possibly first part). Similar to the N-terminal domain of ma 713 698 database:587
Rv1105 Rv1105, (MTV017.58), len: 171 aa. Possible para-nitrobenzyl esterase (fragment; possibly second part). Similar to C-terminal domain of many 711 696 database:587
Rv1990A Rv1990A, len: 111 aa. Possible dehydrogenase (fragment), similar to N-terminal part of several dehydrogenases and hypothetical proteins, e.g 681 681 ctx cooccurence:477
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 657 655 database:584
Rv1004c membrane protein 630 631 ctx cooccurence:627
Rv3350c PPE56 PPE family protein PPE56 621 621 ctx cooccurence:620
Rv0355c PPE8 PPE family protein PPE8 621 621 ctx cooccurence:620
Rv3347c PPE55 PPE family protein PPE55 617 617 ctx cooccurence:616
Rv3372 otsB2 trehalose 6-phosphate phosphatase 613 610 database:584
Rv0304c PPE5 PPE family protein PPE5 608 609 ctx cooccurence:607
Rv2337c hyp hypothetical protein 599 600 ctx cooccurence:529
Rv2124c metH methionine synthase 618 588 database:572

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): Peptidase_M28 PF04389.23 (E=1e-12)
  • (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_216286.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M28 (PF04389.23)
  • 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 COG2234
  • Curated reference: UniProt O06803 (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 — 136 functional partner(s); context anchor Rv1771
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1770|
MDEAHPAHPADAGRPGGPIQGARRGAAMTPITALPTELAAMREVVETLAPIERAAGEPGEHKAAEWIVERLRTAGAQDARIEEEQYLDGYPRLHLKLSVIGVAAGVAGLLSRRLRIPAALAGVGAGLAIADDCANGPRIVRKRTETPRTTWNAVAEAGDPAGQLTVVVCAHHDAAHSGKFFEAHIEEVMVELFPGIVERIDTQLPNWWGPILAPALAGVGALRGSRPMMIAGTVGSALAAALFADIARSPVVPGANDNLSAVALLVALAERLRERPVKGVRVLLVSLGAEETLQGGIYGFLARHKPELDRDRTYFLNFDTIGSPELIMLEGEGPTVMEDYFYRPFRDLVIRAAERADAPLRRGIRSRNSTDAVLMSRAGYPTACFVSINRHKSVANYHLMSDTPENLCYETVSHAVTVAESVIRELAR