Rv3722c Resolved · high auto-curated

H37Rv Rv3722c · MTBC0 mtbc0_003945 · 435 aa · 4190942–4192249 (-) · RefSeq NP_218239.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationaminotransferase
Revised (this work)Aminotransferase. Pfam: Asp_aminotransf (PF12897.14).

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

Curated reference (UniProt)

UniProt O69689 SwissProt · reviewed · Evidence at protein level
UniProt nameAspartate aminotransferase
EC (curated) EC 2.6.1.1
Curated functionMain aspartate aminotransferase that couples nitrogen assimilation to aspartate synthesis. Has a weak, but significant, side activity toward kynurenine (Kyn). Oxaloacetate and 2-oxoglutarate, but not pyruvate, serve as amino acceptors, while Asp, Glu and Kyn serve as the best amino donors. Essential for axenic growth and survival of M.tuberculosis in macrophages and in mice.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
K Transcription
Preferred nameaspT
eggNOG descriptionCOG1167 Transcriptional regulators containing a DNA-binding HTH domain and an aminotransferase domain (MocR family) and their eukaryotic orthologs
Orthologous groupCOG1167

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 2.674 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 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
Asp_aminotransfPF12897.14 1.4e-1846–425 Aspartate amino-transferase

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

Closest characterised functional partner: dnaZX (DNA polymerase III subunit gamma/tau), high confidence from genomic context alone (score 780 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3721c dnaZX DNA polymerase III subunit gamma/tau 780 780 ctx neighborhood:779
Rv2230c GTP cyclohydrolase 510 511 coexpression:507
Rv3723 lucA transmembrane protein 510 510 ctx neighborhood:507
Rv3464 rmlB dTDP-glucose 4,6-dehydratase 447 408 coexpression:408
Rv3784 dTDP-glucose 4,6-dehydratase 400 401 coexpression:401
Rv1085c hemolysin-like protein 716 210 textmining:656
Rv3802c membrane protein 694 197 textmining:635
Rv2704 hyp hypothetical protein 454 165
Rv3256c hyp hypothetical protein 402 47
Rv3192 hyp hypothetical protein 432 41 textmining:432

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: hypothetical protein
  • MTBC0 PGAP product: aminotransferase
  • Pfam (hmmscan --cut_ga): Asp_aminotransf PF12897.14 (E=1e-184)
  • (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_218239.2)
  • Domains: Pfam-A via hmmscan --cut_ga — Asp_aminotransf (PF12897.14)
  • 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 COG1167
  • Curated reference: UniProt O69689 (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 — 10 functional partner(s); context anchor dnaZX
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003945|Rv3722c|
MSFDSLSPQELAALHARHQQDYAALQGMKLALDLTRGKPSAEQLDLSNQLLSLPGDDYRDPEGTDTRNYGGQHGLPGLRAIFAELLGIAVPNLIAGNNSSLELMHDIVAFSMLYGGVDSPRPWIQEQDGIKFLCPVPGYDRHFAITETMGIEMIPIPMLQDGPDVDLIEELVAVDPAIKGMWTVPVFGNPSGVTYSWETVRRLVQMRTAAPDFRLFWDNAYAVHTLTLDFPRQVDVLGLAAKAGNPNRPYVFASTSKITFAGGGVSFFGGSLGNIAWYLQYAGKKSIGPDKVNQLRHLRFFGDADGVRLHMLRHQQILAPKFALVAEVLDQRLSESKIASWTEPKGGYFISLDVLPGTARRTVALAKDVGIAVTEAGASFPYRKDPDDKNIRIAPSFPSVPDLRNAVDGLATCALLAATETLLNQGLASSAPNVR