Rv3712 Family assigned · medium auto-curated

H37Rv Rv3712 · MTBC0 mtbc0_003935 · 413 aa · 4181102–4182343 (+) · RefSeq NP_218229.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ligase
MTBC0 PGAP re-annotationMur ligase family protein
Revised (this work)Mur ligase family protein. Pfam: Mur_ligase_M (PF08245.19), MurT_C (PF08353.16).

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

Curated reference (UniProt)

UniProt I6Y4C7 TrEMBL · unreviewed · Evidence at protein level
UniProt nameLipid II isoglutaminyl synthase
EC (curated) EC 6.3.5.13
Curated functionThe lipid II isoglutaminyl synthase complex catalyzes the formation of alpha-D-isoglutamine in the cell wall lipid II stem peptide. The MurT subunit catalyzes the ATP-dependent amidation of D-glutamate residue of lipid II, converting it to an isoglutamine residue.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG descriptionUDP-N-acetylmuramyl tripeptide synthase
Orthologous groupCOG0769

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 0.447 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 6 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
Mur_ligase_MPF08245.19 1.7e-1456–185 Mur ligase middle domain
MurT_CPF08353.16 1.8e-22303–401 MurT ligase C-terminal

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

Closest characterised functional partner: cobQ2 (cobyric acid synthase CobQ), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3713 cobQ2 cobyric acid synthase CobQ 999 1000 ctx neighborhood:882 fusion:872 cooccurence:774 experimental:817 database:900 textmining:907
Rv2153c murG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase 961 956 coexpression:416 database:900
Rv3711c dnaQ DNA polymerase III subunit epsilon 903 741 ctx neighborhood:739 textmining:641
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 741 668 coexpression:649
Rv2155c murD UDP-N-acetylmuramoylalanine--D-glutamate ligase 676 633 coexpression:550
Rv2163c pbpB penicillin-binding membrane protein PbpB 575 549 coexpression:445
Rv1302 rfe decaprenyl-phosphate N-acetylglucosaminephosphotransferase 513 467 coexpression:449
Rv2156c murX phospho-N-acetylmuramoyl-pentappeptidetransferase 512 466 coexpression:448
Rv2864c penicillin-binding lipoprotein 497 465 coexpression:447
Rv0016c pbpA penicillin-binding protein PbpA 492 460 coexpression:442
Rv2151c ftsQ cell division protein FtsQ 717 453 coexpression:422 textmining:504
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 717 453 coexpression:422 textmining:505
Rv3802c membrane protein 437 437 ctx cooccurence:430
Rv2981c ddlA D-alanine--D-alanine ligase 503 436 coexpression:404
Rv3267 lcp1 hyp hypothetical protein 409 407

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: ligase
  • MTBC0 PGAP product: Mur ligase family protein
  • Pfam (hmmscan --cut_ga): Mur_ligase_M PF08245.19 (E=2e-14), MurT_C PF08353.16 (E=2e-22)
  • (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_218229.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Mur_ligase_M (PF08245.19), MurT_C (PF08353.16)
  • 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 COG0769
  • Curated reference: UniProt I6Y4C7 (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 — 30 functional partner(s); context anchor cobQ2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003935|Rv3712|
MVTTRARLALAAGAGARWASRVTGRGAGAMIGGLVAMTLDRSILRQLGMGRRTVVVTGTNGKSTTTRMTAAALGTLGAVATNAEGANMDAGLVAALAAHRDAELAVLEVDEMHVPHISDAVDPAVVVLLNLSRDQLDRVGEINVIERTLRAGLARHPDAVVVANCDDVLMTSAAYDSPNVVWVAAGGAWSNDSVSCPRSGEVIVRKAPSQEDHWYSTGADFKRPAPHWWFDDATLYGPDGLALPMRLALPGSVNRGNAAQAVAAAVALGADPAVAVAAVCQVDEVAGRYRTVRIGAHQARILLAKNPAGWQEALAMVDKHADGVVIAVNGRVPDGEDLSWLWDVRFEHFEKTRVVAAGERGTDLAVRLGYAGVEHTLVHDTVAAIASCPPGRVEVVANYTAFLQLQRALARRG