MTBC Gene Atlas

Rv0203 Resolved · high

H37Rv Rv0203 · MTBC0 mtbc0_000217 · 136 aa · 241866–242276 (+) · RefSeq NP_214717.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhemophore
Revised (this work)Secreted heme-binding hemophore (Pfam MHB PF16525). Captures host-derived heme and delivers it across the cell envelope for iron acquisition, a component of the mycobacterial heme-uptake system important for growth on heme as an iron source.

Curated reference (UniProt)

UniProt I6X8R5 SwissProt · reviewed · Evidence at protein level
UniProt nameHeme-binding protein Rv0203
Curated functionPart of a heme-iron acquisition system. Acts by binding heme and delivering it to the membrane proteins MmpL3 and MmpL11. Can use free heme or heme from host hemoglobin.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionHaemophore, haem-binding
Orthologous group2APGR
KEGG orthology K20467

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 3 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
MHBPF16525.11 3.1e-2839–115 Haemophore, haem-binding

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

Closest characterised functional partner: mmpL11 (transmembrane transport protein MmpL11), medium confidence from genomic context alone (score 512 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0201c hyp hypothetical protein 713 513 ctx neighborhood:506 textmining:435
Rv0202c mmpL11 transmembrane transport protein MmpL11 875 512 ctx neighborhood:507 textmining:756
Rv0206c mmpL3 transmembrane transport protein MmpL3 527 50 textmining:523
Rv3533c PPE62 PPE family protein PPE62 692 47 textmining:691
Rv1157c hyp hypothetical protein 441 47 textmining:438
Rv0451c mmpS4 membrane protein MmpS4 437 47 textmining:434
Rv0265c iron ABC transporter substrate-binding lipoprotein 415 47 textmining:412
Rv3592 mhuD heme-degrading monooxygenase 870 45 textmining:870
Rv0603 hyp hypothetical protein 696 44 textmining:696
Rv2253 hyp hypothetical protein 543 44 textmining:542
Rv2108 PPE36 PPE family protein PPE36 475 44 textmining:474
Rv1271c hyp hypothetical protein 696 41 textmining:696
Rv1804c hyp hypothetical protein 696 41 textmining:696
Rv2224c caeA carboxylesterase A 594 41 textmining:594
Rv2223c caeB carboxylesterase B 485 41 textmining:485

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

  • MTBC0 PGAP product: 'hemophore'
  • Pfam: MHB PF16525 (E=3.1e-28) -- mycobacterial heme-binding hemophore domain

ESM Atlas signal (exploratory)

Ancestral protein hash a922ef2d6d78fd1b1d8177e864359f1b · 10 ESM-space neighbours (max similarity 0.944). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
114827 0.84 Signal peptide cleavage neighborhood
214762 0.82 Extracytosolic low-complexity repeats
312515 0.71 Secreted alpha-helical subdomains
411267 0.68 Signal peptides and sortase anchors
59806 0.67 Mature secreted N-terminus
67904 0.67 Terminal helices and disordered tails
712641 0.62 Secreted helical interaction surfaces
814128 0.49 Mature extracellular functional domains

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_214717.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MHB (PF16525.11)
  • 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 2APGR
  • Curated reference: UniProt I6X8R5 (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 — 17 functional partner(s); context anchor mmpL11
  • Primary literature: Tullius MV et al. (2011). Discovery and characterization of a unique mycobacterial heme acquisition system PNAS. doi:10.1073/pnas.1009516108 PMID:21383189

Ancestral MTBC0 protein sequence

>mtbc0_000217|Rv0203|
MKTGTATTRRRLLAVLIALALPGAAVALLAEPSATGASDPCAASEVARTVGSVAKSMGDYLDSHPETNQVMTAVLQQQVGPGSVASLKAHFEANPKVASDLHALSQPLTDLSTRCSLPISGLQAIGLMQAVQGARR