Rv3273 Resolved · high auto-curated

H37Rv Rv3273 · MTBC0 - · 764 aa · 3654637–3656931 (+) · RefSeq NP_217790.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane carbonic anhydrase
MTBC0 PGAP re-annotation
Revised (this work)Transmembrane carbonic anhydrase. Pfam: Sulfate_transp (PF00916.27), Pro_CA (PF00484.25).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P96878 TrEMBL · unreviewed · Evidence at protein level
UniProt namecarbonic anhydrase
EC (curated) EC 4.2.1.1
Curated functionCatalyzes the reversible hydration of carbon dioxide to form bicarbonate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred namest2
eggNOG descriptionTransporter
Orthologous groupCOG0288
EC number EC 4.2.1.1
KEGG orthology K01673, K03321
KEGG pathways map00910

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 0.213 · purifying
Polymorphic sites (≥ 0.1% of strains) 12 synonymous, 7 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
Sulfate_transpPF00916.27 1.9e-8531–398 Sulfate permease family
Pro_CAPF00484.25 2.8e-39580–739 Carbonic anhydrase

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

Closest characterised functional partner: Rv3271c (integral membrane protein), medium confidence from genomic context alone (score 603 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3588c canB carbonic anhydrase 967 918 database:900 textmining:623
Rv1284 canA beta-carbonic anhydrase 970 914 database:900 textmining:675
Rv2048c pks12 polyketide synthase 842 821 experimental:772
Rv3272 hyp hypothetical protein 820 820 ctx neighborhood:810
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 816 791 experimental:772
Rv2940c mas multifunctional mycocerosic acid synthase 816 791 experimental:772
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 816 790 experimental:772
Rv1527c pks5 polyketide synthase 816 790 experimental:772
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 799 787 experimental:774
Rv1663 pks17 polyketide synthase 795 783 experimental:772
Rv0153c ptbB phosphotyrosine protein phosphatase 760 761 experimental:749
Rv3157 nuoM NADH-quinone oxidoreductase subunit M 770 700 experimental:648
Rv1277 hyp hypothetical protein 699 700 experimental:681
Rv2584c apt adenine phosphoribosyltransferase 666 652 coexpression:640
Rv3271c integral membrane protein 619 603 ctx neighborhood:597

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): transmembrane carbonic anhydrase
  • Pfam (hmmscan --cut_ga): Sulfate_transp PF00916.27 (E=2e-85), Pro_CA PF00484.25 (E=3e-39)
  • (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_217790.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sulfate_transp (PF00916.27), Pro_CA (PF00484.25)
  • 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 COG0288
  • Curated reference: UniProt P96878 (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 — 65 functional partner(s); context anchor Rv3271c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3273|
MTIPRSQHMSTAVNSCTEAPASRSQWMLANLRHDVPASLVVFLVALPLSLGIAIASGAPIIAGVIAAVVGGIVAGAVGGSPVQVSGPAAGLTVVVAELIDELGWPMLCLMTIAAGALQIVFGLSRMARAALAIAPVVVHAMLAGIGITIALQQIHVLLGGTSHSSAWRNIVALPDGILHHELHEVIVGGTVIAILLMWSKLPAKVRIIPGPLVAIAGATVLALLPVLQTERIDLQGNFFDAIGLPKLAEMSPGGQPWSHEISAIALGVLTIALIASVESLLSAVGVDKLHHGPRTDFNREMVGQGSANVVSGLLGGLPITGVIVRSSANVAAGARTRMSTILHGVWILLFASLFTNLVELIPKAALAGLLIVIGAQLVKLAHIKLAWRTGNFVIYAITIVCVVFLNLLEGVAIGLVVAIVFLLVRVVRAPVEVKPVGGEQSKRWRVDIDGTLSFLLLPRLTTVLSKLPEGSEVTLNLNADYIDDSVSEAISDWRRAHETRGGVVAIVETSPAKLHHAHARPPKRHFASDPIGLVPWRSARGKDRGSASVLDRIDEYHRNGAAVLHPHIAGLTDSQDPYELFLTCADSRILPNVITASGPGDLYTVRNLGNLVPTDPDDRSVDAALDFAVNQLGVSSVVVCGHSSCAAMTALLEDDPANTTTPMMRWLENAHDSLVVFRNHHPARRSAESAGYPEADQLSIVNVAVQVERLTRHPILATAVAAADLQVIGIFFDISTARVYEVGPNGIICPDEPADRPVDHESAQ