Rv0142 Resolved · medium

H37Rv Rv0142 · MTBC0 mtbc0_000153 · 308 aa · 168057–168983 (+) · RefSeq NP_214656.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDNA-3-methyladenine glycosylase
Revised (this work)DNA-3-methyladenine glycosylase: a base-excision-repair enzyme that removes alkylated bases (e.g. 3-methyladenine) from DNA, initiating their repair. Assigned by RefSeq/PGAP homology (no Pfam domain above the gathering threshold).

Curated reference (UniProt)

UniProt P96819 TrEMBL · unreviewed · Predicted
UniProt nameDNA-3-methyladenine glycosylase II
EC (curated) EC 3.2.2.21

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionDNA glycosylase
Orthologous groupCOG0122

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 0.162 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 3 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: rslA (anti-sigma-L factor RslA), medium confidence from genomic context alone (score 535 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0427c xthA exodeoxyribonuclease III protein XthA 757 725 database:651
Rv0141c hyp hypothetical protein 618 617 ctx neighborhood:615
Rv0736 rslA anti-sigma-L factor RslA 535 535 ctx cooccurence:521
Rv3731 ligC DNA ligase C 544 515 ctx cooccurence:485
Rv3202c adnA ATP-dependent DNA helicase 502 475
Rv3062 ligB DNA ligase 479 446 ctx cooccurence:404
Rv0786c hyp hypothetical protein 442 443 ctx cooccurence:425
Rv0670 end endonuclease IV 503 436
Rv1171 hyp hypothetical protein 424 425 ctx cooccurence:407
Rv1635c mannosyltransferase 422 422 ctx cooccurence:404
Rv2090 5'-3' exonuclease 409 354
Rv1629 polA DNA polymerase I 480 265
Rv3197A whiB7 transcriptional regulator WhiB7 555 54 textmining:549
Rv0102 integral membrane protein 871 53 textmining:870
Rv1911c lppC lipoprotein LppC 519 50 textmining:515

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

  • MTBC0 PGAP product: 'DNA-3-methyladenine glycosylase'
  • Pfam: no domain above cut_ga; assignment from RefSeq/PGAP homology

ESM Atlas signal (exploratory)

Ancestral protein hash 02cf801cc7770368a4456da256100aec · 10 ESM-space neighbours (max similarity 0.879). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
19583 1.43 HhH-GPD DNA glycosylase core
29822 1.23 HhH glycosylase DNA-binding helix
38366 1.16 DNA glycosylase catalytic cores
412414 1.03 N-terminal DNA entry module
56660 0.93 Glycosylase C-terminal lesion-recognition
614043 0.87 Terminal IDRs in DNA repair
76006 0.79 Small-residue hinge detector
815399 0.78 DNA glycosylase catalytic helix-loop

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_214656.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0122
  • Curated reference: UniProt P96819 (TrEMBL, unreviewed; Predicted)
  • 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 — 16 functional partner(s); context anchor rslA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000153|Rv0142|
MRSIDVVVEAVVTFAGAAGFAHTLAPLRRGQQDPCFRVPGDGTIWRTSLLPTGPVTARISRAGRDAARCVAWGSGAEEFVDMAPAMLGAADDASDFVPLHPAVAAAHRRLPNLRLGRTGQVLEALIPAVIEQRVPGADAFRSWRLLVSKYGTQAPGPAPPGMRVPPSAEVWRHIPSWEFHRANVDPGRARAVVGCAQRAASLERLVSLPAARAAEALTSLPGVGVWTAAETTQRVFGDADAVSVGDYHIPKMIGWTLVGRPVDDAGMLELLEPMRPHRHRVVRLLEASGLAREPRRGPRLPVQNIRAL