Rv0435c Family assigned · medium auto-curated

H37Rv Rv0435c · MTBC0 mtbc0_000457 · 728 aa · 525712–527898 (-) · RefSeq NP_214949.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ATPase
MTBC0 PGAP re-annotationAAA family ATPase
Revised (this work)AAA family ATPase. Pfam: CDC48_N (PF02359.25), AAA (PF00004.36), AAA_lid_3 (PF17862.8).

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

Curated reference (UniProt)

UniProt P96281 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved ATPase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionBelongs to the AAA ATPase family
Orthologous groupCOG0464
KEGG orthology K13525
KEGG pathways map04141, map05134
KEGG modules M00400, M00403

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 0.217 · purifying
Polymorphic sites (≥ 0.1% of strains) 13 synonymous, 6 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (178) · 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
CDC48_NPF02359.25 9.8e-1322–94 Cell division protein 48 (CDC48), N-terminal domain
AAAPF00004.36 1.1e-38501–631 ATPase family associated with various cellular activities (AAA)
AAA_lid_3PF17862.8 2.2e-10654–698 AAA+ lid domain

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

Closest characterised functional partner: pssA (CDP-diacylglycerol--serine O-phosphatidyltransferase), high confidence from genomic context alone (score 896 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0436c pssA CDP-diacylglycerol--serine O-phosphatidyltransferase 896 896 ctx neighborhood:881
Rv0437c psd phosphatidylserine decarboxylase 888 884 ctx neighborhood:881
Rv0438c moeA2 molybdopterin molybdenumtransferase 812 804 ctx neighborhood:802
Rv1349 irtB iron ABC transporter ATP-binding protein/permease IrtB 809 800 ctx cooccurence:429 database:528
Rv2110c prcB proteasome subunit beta 785 772 experimental:406 database:537
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 773 745 database:528
Rv3696c glpK glycerol kinase 744 745 database:606
Rv2109c prcA proteasome subunit alpha 756 741 experimental:406 database:537
Rv2115c mpa proteasome-associated ATPase 717 717 database:566
Rv0439c dehydrogenase/reductase 708 707 ctx neighborhood:613
Rv1334 mec [CysO 707 690 database:502
Rv0350 dnaK chaperone protein DnaK 703 688 database:468
Rv2861c mapB methionine aminopeptidase 696 677 database:442
Rv1272c drug ABC transporter ATP-binding protein 691 676 database:528
Rv1819c bacA vitamin B12 transport ATP-binding protein BacA 690 673 database:617

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: ATPase
  • MTBC0 PGAP product: AAA family ATPase
  • Pfam (hmmscan --cut_ga): CDC48_N PF02359.25 (E=1e-12), AAA PF00004.36 (E=1e-38), AAA_lid_3 PF17862.8 (E=2e-10)
  • (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_214949.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CDC48_N (PF02359.25), AAA (PF00004.36), AAA_lid_3 (PF17862.8)
  • 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 COG0464
  • Curated reference: UniProt P96281 (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 — 135 functional partner(s); context anchor pssA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000457|Rv0435c|
MTHPDPARQLTLTARLNTSAVDSRRGVVRLHPNAIAALGIREWDAVSLTGSRTTAAVAGLAAADTAVGTVLLDDVTLSNAGLREGTEVIVSPVTVYGARSVTLSGSTLATQSVPPVTLRQALLGKVMTVGDAVSLLPRDLGPGTSTSAASRALAAAVGISWTSELLTVTGVDPDGPVSVQPNSLVTWGAGVPAAMGTSTAGQVSISSPEIQIEELKGAQPQAAKLTEWLKLALDEPHLLQTLGAGTNLGVLVSGPAGVGKATLVRAVCDGRRLVTLDGPEIGALAAGDRVKAVASAVQAVRHEGGVLLITDADALLPAAAEPVASLILSELRTAVATAGVVLIATSARPDQLDARLRSPELCDRELGLPLPDAATRKSLLEALLNPVPTGDLNLDEIASRTPGFVVADLAALVREAALRAASRASADGRPPMLHQDDLLGALTVIRPLSRSASDEVTVGDVTLDDVGDMAAAKQALTEAVLWPLQHPDTFARLGVEPPRGVLLYGPPGCGKTFVVRALASTGQLSVHAVKGSELMDKWVGSSEKAVRELFRRARDSAPSLVFLDELDALAPRRGQSFDSGVSDRVVAALLTELDGIDPLRDVVMLGATNRPDLIDPALLRPGRLERLVFVEPPDAAARREILRTAGKSIPLSSDVDLDEVAAGLDGYSAADCVALLREAALTAMRRSIDAANVTAADLATARETVRASLDPLQVASLRKFGTKGDLRS