arfA Family assigned · medium auto-curated

H37Rv Rv0899 · MTBC0 mtbc0_000953 · 326 aa · 1006026–1007006 (+) · RefSeq NP_215414.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)peptidoglycan-binding protein ArfA
MTBC0 PGAP re-annotationpeptidoglycan-binding protein ArfA
Revised (this work)Peptidoglycan-binding protein ArfA. Pfam: BON_like (PF21923.2), BON (PF04972.23), OmpA (PF00691.26).

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

Curated reference (UniProt)

UniProt P9WIU5 SwissProt · reviewed · Evidence at protein level
UniProt namePeptidoglycan-binding protein ArfA
Curated functionProbably plays a role in ammonia secretion that neutralizes the medium at pH 5.5, although it does not play a direct role in ammonia transport. The OmpA-like domain (196-326) binds M.tuberculosis peptidoglycan. Overexpression in M.bovis or M.smegmatis gives channels with average conductance value of 1,600 +/- 100 pS, but this may not be physiologically relevant.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameompA
eggNOG descriptionBelongs to the ompA family
Orthologous groupCOG2885
KEGG orthology K16191
Gene Ontology (60) GO:0003674, GO:0005215, GO:0005488, GO:0005539, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0005887 +48 more

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 1.435 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (194) · 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
BON_likePF21923.2 2.7e-2582–128 BON-like domain
BONPF04972.23 4.1e-06150–195 BON domain
OmpAPF00691.26 1.2e-22225–319 OmpA family

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

Closest characterised functional partner: arfC (membrane protein), high confidence from genomic context alone (score 905 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0901 arfC membrane protein 986 905 ctx neighborhood:869 textmining:861
Rv0898c hyp hypothetical protein 780 780 ctx neighborhood:779
Rv0900 arfB membrane protein 969 777 ctx neighborhood:777 textmining:870
Rv0897c oxidoreductase 759 759 ctx neighborhood:758
Rv0053 rpsF 30S ribosomal protein S6 631 632 experimental:405
Rv1157c hyp hypothetical protein 654 611
Rv0056 rplI 50S ribosomal protein L9 581 565 experimental:405
Rv0341 iniB isoniazid inducible protein IniB 576 557
Rv2098c PE_PGRS36 PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub 532 533
Rv3443c rplM 50S ribosomal protein L13 531 532 experimental:405
Rv1288 hyp hypothetical protein 559 531
Rv0979A rpmF 50S ribosomal protein L32 528 528 experimental:405
Rv0682 rpsL 30S ribosomal protein S12 565 527 experimental:405
Rv2890c rpsB 30S ribosomal protein S2 547 525 experimental:405
Rv0720 rplR 50S ribosomal protein L18 523 524 experimental:405

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: peptidoglycan-binding protein ArfA
  • MTBC0 PGAP product: peptidoglycan-binding protein ArfA
  • Pfam (hmmscan --cut_ga): BON_like PF21923.2 (E=3e-25), BON PF04972.23 (E=4e-06), OmpA PF00691.26 (E=1e-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_215414.1)
  • Domains: Pfam-A via hmmscan --cut_ga — BON_like (PF21923.2), BON (PF04972.23), OmpA (PF00691.26)
  • 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 COG2885
  • Curated reference: UniProt P9WIU5 (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 — 82 functional partner(s); context anchor arfC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000953|Rv0899|arfA
MASKAGLGQTPATTDARRTQKFYRGSPGRPWLIGAVVIPLLIAAIGYGAFERPQSVTGPTGVLPTLTPTSTRGASALSLSLLSISRSGNTVTLIGDFPDEAAKAALMTALNGLLAPGVNVIDQIHVDPVVRSLDFSSAEPVFTASVPIPDFGLKVERDTVTLTGTAPSSEHKDAVKRAATSTWPDMKIVNNIEVTGQAPPGPPASGPCADLQSAINAVTGGPIAFGNDGASLIPADYEILNRVADKLKACPDARVTINGYTDNTGSEGINIPLSAQRAKIVADYLVARGVAGDHIATVGLGSVNPIASNATPEGRAKNRRVEIVVN