proC Resolved · high auto-curated
H37Rv Rv0500 · MTBC0 - ·
295 aa · 590083–590970 (+) ·
RefSeq NP_215014.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyrroline-5-carboxylate reductase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Pyrroline-5-carboxylate reductase. Pfam: F420_oxidored (PF03807.24), NAD_binding_2 (PF03446.22), P5CR_dimer (PF14748.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WHU7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Pyrroline-5-carboxylate reductase |
| EC (curated) |
EC 1.5.1.2
|
| Curated function | Catalyzes the reduction of 1-pyrroline-5-carboxylate (PCA) to L-proline. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | proC |
| eggNOG description | Catalyzes the reduction of 1-pyrroline-5-carboxylate (PCA) to L-proline |
| Orthologous group | COG0345 |
| EC number |
EC 1.5.1.2
|
| KEGG orthology |
K00286
|
| KEGG pathways |
map00330, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00015
|
| Gene Ontology (52) |
GO:0000287, GO:0003674, GO:0003824, GO:0004735, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006560, GO:0006561 +40 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 | 0.075 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 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 |
|---|---|---|---|---|
F420_oxidored | PF03807.24 | 6.6e-19 | 7–105 | NADP oxidoreductase coenzyme F420-dependent |
NAD_binding_2 | PF03446.22 | 7.1e-05 | 7–85 | NAD binding domain of 6-phosphogluconate dehydrogenase |
P5CR_dimer | PF14748.12 | 3.1e-34 | 169–290 | Pyrroline-5-carboxylate reductase dimerisation |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: proB (glutamate 5-kinase protein), high confidence from genomic context alone (score 832 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1188 |
proline dehydrogenase | 990 | 924 | database:900 textmining:880 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 957 | 905 | database:900 textmining:570 |
Rv0840c pip |
proline iminopeptidase | 903 | 903 | database:900 |
Rv0499 hyp |
hypothetical protein | 847 | 848 ctx | neighborhood:846 |
Rv2439c proB |
glutamate 5-kinase protein | 945 | 832 ctx | cooccurence:660 coexpression:422 textmining:688 |
Rv0498 hyp |
hypothetical protein | 831 | 831 ctx | neighborhood:830 |
Rv0496 ppx1 hyp |
hypothetical protein | 816 | 816 ctx | neighborhood:815 |
Rv0497 |
transmembrane protein | 815 | 816 ctx | neighborhood:815 |
Rv2427c proA |
gamma-glutamyl phosphate reductase | 936 | 802 ctx | cooccurence:676 textmining:695 |
Rv0500A |
DNA-binding protein | 744 | 744 ctx | neighborhood:742 |
Rv0495c hyp |
hypothetical protein | 737 | 737 ctx | neighborhood:737 |
Rv0500B |
Rv0500B, len: 33 aa. Conserved hypothetical protein. Basic protein 18 of the 33 aa are Arg or Lys, with strong similarity to AL079345|SCE68_ | 465 | 464 ctx | neighborhood:461 |
Rv2146c |
transmembrane protein | 436 | 436 | |
Rv2148c hyp |
hypothetical protein | 478 | 424 | |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 414 | 340 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): pyrroline-5-carboxylate reductase
- Pfam (hmmscan --cut_ga): F420_oxidored PF03807.24 (E=7e-19), NAD_binding_2 PF03446.22 (E=7e-05), P5CR_dimer PF14748.12 (E=3e-34)
- (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_215014.1)
- Domains: Pfam-A via hmmscan --cut_ga — F420_oxidored (PF03807.24), NAD_binding_2 (PF03446.22), P5CR_dimer (PF14748.12)
- 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
COG0345 - Curated reference: UniProt P9WHU7 (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 —
42 functional partner(s); context anchor
proB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0500|proC MLFGMARIAIIGGGSIGEALLSGLLRAGRQVKDLVVAERMPDRANYLAQTYSVLVTSAADAVENATFVVVAVKPADVEPVIADLANATAAAENDSAEQVFVTVVAGITIAYFESKLPAGTPVVRAMPNAAALVGAGVTALAKGRFVTPQQLEEVSALFDAVGGVLTVPESQLDAVTAVSGSGPAYFFLLVEALVDAGVGVGLSRQVATDLAAQTMAGSAAMLLERMEQDQGGANGELMGLRVDLTASRLRAAVTSPGGTTAAALRELERGGFRMAVDAAVQAAKSRSEQLRITPE