Rv1995 Family assigned · medium auto-curated

H37Rv Rv1995 · MTBC0 mtbc0_002122 · 255 aa · 2261754–2262521 (+) · RefSeq NP_216511.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhemerythrin domain-containing protein
Revised (this work)Hemerythrin domain-containing protein. Pfam: Hemerythrin (PF01814.29).

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

Curated reference (UniProt)

UniProt P9WLP3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1995

UniProt still lists this protein as Uncharacterized protein Rv1995; 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 descriptionHemerythrin HHE cation binding domain
Orthologous groupCOG3945
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 1.632 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 3.34% of strains (4843) · 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
HemerythrinPF01814.29 2.2e-1569–201 Hemerythrin HHE cation binding domain

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

Closest characterised functional partner: Rv1996 (universal stress protein), medium confidence from genomic context alone (score 580 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1996 universal stress protein 706 580 ctx neighborhood:578
Rv0470A hyp hypothetical protein 543 544 ctx cooccurence:543
Rv1994c cmtR HTH-type transcriptional regulator CmtR 732 539 ctx neighborhood:528 textmining:443
Rv0665 vapC8 ribonuclease VapC8 484 484 ctx cooccurence:484
Rv3479 transmembrane protein 464 464 ctx cooccurence:464
Rv2337c hyp hypothetical protein 452 452 ctx cooccurence:446
Rv1992c ctpG cation transporter ATPase G 636 445 ctx neighborhood:440
Rv0626 vapB5 antitoxin VapB5 436 436 ctx cooccurence:436
Rv1993c hyp hypothetical protein 918 430 ctx neighborhood:425 textmining:862
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 427 427 ctx cooccurence:427
Rv1979c permease 434 194
Rv1673c hyp hypothetical protein 613 180 textmining:548
Rv1521 fadD25 fatty-acid--CoA ligase FadD25 511 164 textmining:440
Rv2075c hyp hypothetical protein 602 159 textmining:547
Rv2434c transmembrane protein 563 71 textmining:549

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: hemerythrin domain-containing protein
  • Pfam (hmmscan --cut_ga): Hemerythrin PF01814.29 (E=2e-15)
  • (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_216511.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Hemerythrin (PF01814.29)
  • 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 COG3945
  • Curated reference: UniProt P9WLP3 (SwissProt, reviewed; 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 Rv1996
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002122|Rv1995|
MVASGAATKGVTVMKQTPPAAVGRRHLLEISASAAGVIALSACSGSPPEPGKGRPDTTPEQEVPVTAPEDLMREHGVLKRILLIYREGIRRLQADDQSPAPALNESAQIIRRFIEDYHGQLEEQYVFPKLEQAGKLTDITSVLRTQHQRGRVLTDRVLAATTAAAAFDQPARDTLAQDMAAYIRMFEPHEAREDTVVFPALRDVMSAVEFRDMAETFEDEEHRRFGEAGFQSVVDKVADIEKSLGIYDLSQFTPS