Rv2004c Family assigned · medium auto-curated
H37Rv Rv2004c · MTBC0 mtbc0_002132 ·
498 aa · 2273091–2274587 (-) ·
RefSeq NP_216520.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | AAA family ATPase |
| Revised (this work) | AAA family ATPase. Pfam: Zeta_toxin (PF06414.19), AAA_33 (PF13671.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WLN3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2004c |
| Curated function | Some isolated peptides of this protein are able to bind to human U937 monocytoblastic and A549 epithelial cell lines. |
UniProt still lists this protein as Uncharacterized protein Rv2004c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | AAA domain |
| Orthologous group | COG0645 |
| KEGG orthology |
K07028
|
| Gene Ontology (13) |
GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0009987, GO:0030312, GO:0044464, GO:0044764, GO:0046812, GO:0051704 +1 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 | 0.192 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 4 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Zeta_toxin | PF06414.19 | 6.2e-06 | 323–426 | Zeta toxin |
AAA_33 | PF13671.13 | 2.9e-17 | 324–461 | AAA domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2005c (universal stress protein), high confidence from genomic context alone (score 967 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2005c |
universal stress protein | 966 | 967 ctx | neighborhood:771 coexpression:860 |
Rv2003c hyp |
hypothetical protein | 978 | 955 ctx | neighborhood:623 coexpression:860 textmining:537 |
Rv2006 otsB1 |
trehalose-6-phosphate phosphatase OtsB | 953 | 953 ctx | neighborhood:762 coexpression:811 |
Rv0571c hyp |
hypothetical protein | 935 | 888 | coexpression:824 textmining:449 |
Rv0570 nrdZ |
vitamin B12-dependent ribonucleoside-diphosphate reductase | 868 | 832 | coexpression:826 |
Rv1997 ctpF |
cation transporter ATPase F | 899 | 828 | coexpression:757 textmining:439 |
Rv3132c devS |
two component sensor histidine kinase DevS | 822 | 811 | coexpression:805 |
Rv2630 hyp |
hypothetical protein | 788 | 788 | coexpression:788 |
Rv2624c |
universal stress protein | 764 | 765 | coexpression:734 |
Rv2629 hyp |
hypothetical protein | 734 | 734 | coexpression:734 |
Rv3133c devR |
two component transcriptional regulator DevR | 834 | 733 | coexpression:732 textmining:404 |
Rv1364c |
sigma factor regulatory protein | 549 | 550 ctx | neighborhood:544 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 546 | 547 ctx | neighborhood:544 |
Rv2031c hspX |
alpha-crystallin | 506 | 507 | |
Rv0251c hsp |
heat shock protein | 501 | 501 |
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: AAA family ATPase
- Pfam (hmmscan --cut_ga): Zeta_toxin PF06414.19 (E=6e-06), AAA_33 PF13671.13 (E=3e-17)
- (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_216520.1)
- Domains: Pfam-A via hmmscan --cut_ga — Zeta_toxin (PF06414.19), AAA_33 (PF13671.13)
- 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
COG0645 - Curated reference: UniProt P9WLN3 (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 —
39 functional partner(s); context anchor
Rv2005c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002132|Rv2004c| MDSPTNDGTCDAHPVTDEPFIDVRETHTAVVVLAGDRAFKAKKPVVTDFCDFRTAEQRERACIREFELNSRLAAQSYLGIAHLSDPSGGHAEPVVVMRRYRDKQRLASMVTAGLPVEGALDAIAEVLARFHQRAQRNRCIDTQGEVGAVARRWHENLAELRHHADKVVSGDVIRRIEHMVDEFVSGREVLFAGRIKEGCIVDGHADLLADDIFLVDGEPALLDCLEFEDELRYLDRIDDAAFLAMDLEFLGRKDLGDYFLAGYAVRSGDTAPASLRDFYIAYRAVVRAKVECVRFSQGKPEAAADAVRHLIIATQHLQHATVRLALVGGNPGTGKSTLARGVAELVGAQVISTDDVRRRLRDCGVITGEPGVLDSGLYSRANVVAVYQEALRKARLLLGSGHSVILDGTWGDPQMRACARRLAADTHSAIVEFRCSATVDVMADRIVARAGGNSDATAEIAAALAARQADWDTGHRIDTAGPRERSVGQAYHIWRSAI