mrr Resolved · high auto-curated

H37Rv Rv2528c · MTBC0 mtbc0_002692 · 306 aa · 2874641–2875561 (-) · RefSeq NP_217044.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)restriction system protein
MTBC0 PGAP re-annotationrestriction endonuclease
Revised (this work)Restriction endonuclease. Pfam: Mrr_N (PF14338.13), Mrr_cat (PF04471.19), NA-iREase1 (PF22722.3), Mrr_cat_2 (PF13156.13).

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

Curated reference (UniProt)

UniProt I6Y9K2 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable restriction system protein Mrr

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namemrr
eggNOG descriptionRestriction endonuclease
Orthologous groupCOG1715
KEGG orthology K07448

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 0.339 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 8 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
Mrr_NPF14338.13 5.2e-297–91 Mrr N-terminal domain
Mrr_catPF04471.19 1.0e-37162–280 Restriction endonuclease
NA-iREase1PF22722.3 1.2e-10169–277 NACHT-associated inactive Restriction Endonuclease 1
Mrr_cat_2PF13156.13 2.9e-06190–283 Restriction endonuclease

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

Closest characterised functional partner: vapC38 (ribonuclease VapC38), medium confidence from genomic context alone (score 410 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2756c hsdM type I restriction/modification system DNA methylase HsdM 643 589 coexpression:423
Rv2529 hyp hypothetical protein 776 498 ctx neighborhood:491 textmining:572
Rv2494 vapC38 ribonuclease VapC38 410 410 ctx cooccurence:410
Rv2755c hsdS.1 Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s 732 367 textmining:594
Rv2761c hsdS type I restriction/modification system specificity determinant HsdS 718 184 textmining:669
Rv1048c hyp hypothetical protein 575 100 textmining:547
Rv2527 vapC17 ribonuclease VapC17 443 61 textmining:432
Rv0620 galK galactokinase 892 52 textmining:892
Rv0325 hyp hypothetical protein 417 52 textmining:411
Rv1833c dhmA2 haloalkane dehalogenase 544 46 textmining:542
Rv0326 hyp hypothetical protein 514 46 textmining:512
Rv1531 hyp hypothetical protein 521 44 textmining:520
Rv2533c nusB N utilization substance protein B 437 44 textmining:436
Rv0682 rpsL 30S ribosomal protein S12 574 42 textmining:574
Rv1767 hyp hypothetical protein 542 42 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: restriction system protein
  • MTBC0 PGAP product: restriction endonuclease
  • Pfam (hmmscan --cut_ga): Mrr_N PF14338.13 (E=5e-29), Mrr_cat PF04471.19 (E=1e-37), NA-iREase1 PF22722.3 (E=1e-10), Mrr_cat_2 PF13156.13 (E=3e-06)
  • (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_217044.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Mrr_N (PF14338.13), Mrr_cat (PF04471.19), NA-iREase1 (PF22722.3), Mrr_cat_2 (PF13156.13)
  • 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 COG1715
  • Curated reference: UniProt I6Y9K2 (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 — 23 functional partner(s); context anchor vapC38
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002692|Rv2528c|mrr
MTIPDAQTLMRPILAYLADGQAKSAKDVIAAMSDEFGLSDDERAQMLPSGRQRTMYDRVHWSLTHMSQAGLLDRPTRGHVQVTDTGRQVLKAHPERVDMAVLREFPSYIAFRERTKAKQPVDATAKRPSGDDVQVSPEDLIDAALAENRAAVEGEILKKALTLSPTGFEDLVIRLLEAMGYGRAGAVERTSASGDAGIDGIISQDPLGLDRIYVQAKRYAVDQTIGRPKIHEFAGALLGKQGDRGVYITTSSFSRGAREEAERINARIELIDGARLAELLVRYRVGVQAVQTVELLRLDEDFFDGL