cuvA Resolved · high auto-curated
H37Rv Rv1422 · MTBC0 mtbc0_001522 ·
342 aa · 1606225–1607253 (+) ·
RefSeq NP_215938.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | carbon utilization/virulence protein CuvA |
| Revised (this work) | Carbon utilization/virulence protein CuvA. Pfam: CofD (PF01933.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMU5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative gluconeogenesis factor |
| Curated function | Required for morphogenesis under gluconeogenic growth conditions. |
UniProt still lists this protein as Putative gluconeogenesis factor; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Required for morphogenesis under gluconeogenic growth conditions |
| Orthologous group | COG0391 |
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 | 0.194 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 2 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 |
|---|---|---|---|---|
CofD | PF01933.24 | 3.4e-73 | 5–283 | 2-phospho-L-lactate transferase CofD |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: whiA (transcriptional regulator WhiA), high confidence from genomic context alone (score 965 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) |
|---|---|---|---|---|
Rv1421 rapZ hyp |
hypothetical protein | 972 | 968 ctx | neighborhood:882 coexpression:743 |
Rv1423 whiA |
transcriptional regulator WhiA | 969 | 965 ctx | neighborhood:882 coexpression:673 |
Rv1420 uvrC |
excinuclease ABC subunit UvrC | 890 | 885 ctx | neighborhood:882 |
Rv1417 |
membrane protein | 691 | 692 ctx | neighborhood:682 |
Rv1416 ribH |
6,7-dimethyl-8-ribityllumazine synthase | 691 | 692 ctx | neighborhood:682 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 687 | 687 ctx | neighborhood:682 |
Rv1419 hyp |
hypothetical protein | 596 | 597 ctx | neighborhood:594 |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 813 | 578 | coexpression:512 textmining:576 |
Rv1460 sufR |
transcriptional regulator | 562 | 562 ctx | cooccurence:557 |
Rv1418 lprH |
lipoprotein LprH | 439 | 439 ctx | neighborhood:435 |
Rv3840 |
transcriptional regulator | 418 | 419 ctx | cooccurence:415 |
Rv1018c glmU |
bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase | 415 | 353 | |
Rv2332 mez |
malate oxidoreductase | 629 | 231 | textmining:538 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 402 | 168 | |
Rv1224 tatB |
Sec-independent protein translocase protein TatB | 680 | 102 | textmining:659 |
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: carbon utilization/virulence protein CuvA
- Pfam (hmmscan --cut_ga): CofD PF01933.24 (E=3e-73)
- (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_215938.1)
- Domains: Pfam-A via hmmscan --cut_ga — CofD (PF01933.24)
- 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
COG0391 - Curated reference: UniProt P9WMU5 (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 —
18 functional partner(s); context anchor
whiA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001522|Rv1422|cuvA MTDGIVALGGGHGLYATLSAARRLTPYVTAVVTVADDGGSSGRLRSELDVVPPGDLRMALAALASDSPHGRLWATILQHRFGGSGALAGHPIGNLMLAGLSEVLADPVAALDELGRILGVKGRVLPMCPVALQIEADVSGLEADPRMFRLIRGQVAIATTPGKVRRVRLLPTDPPATRQAVDAIMAADLVVLGPGSWFTSVIPHVLVPGLAAALRATSARRALVLNLVAEPGETAGFSVERHLHVLAQHAPGFTVHDIIIDAERVPSEREREQLRRTATMLQAEVHFADVARPGTPLHDPGKLAAVLDGVCARDVGASEPPVAATQEIPIDGGRPRGDDAWR