Rv1188 Resolved · high auto-curated

H37Rv Rv1188 · MTBC0 mtbc0_001276 · 329 aa · 1339463–1340452 (+) · RefSeq NP_215704.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)proline dehydrogenase
MTBC0 PGAP re-annotationproline dehydrogenase
Revised (this work)Proline dehydrogenase. Pfam: Pro_dh (PF01619.25).

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

Curated reference (UniProt)

UniProt O50444 TrEMBL · unreviewed · Evidence at protein level
UniProt nameproline dehydrogenase
EC (curated) EC 1.5.5.2

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameputA
eggNOG descriptionProline dehydrogenase
Orthologous groupCOG0506
KEGG orthology K00318
KEGG pathways map00330, map01100, map01110, map01130

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) pseudogene candidate

pN/pS 1.31 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.45% of strains (2111) · 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
Pro_dhPF01619.25 1.6e-3052–312 Proline dehydrogenase

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

Closest characterised functional partner: rocA (pyrroline-5-carboxylate dehydrogenase RocA), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 999 999 ctx neighborhood:882 cooccurence:650 coexpression:830 database:900 textmining:649
Rv0500 proC pyrroline-5-carboxylate reductase 990 924 database:900 textmining:880
Rv0840c pip proline iminopeptidase 901 902 database:900
Rv1186c hyp hypothetical protein 908 840 ctx neighborhood:783 textmining:451
Rv2858c aldC aldehyde dehydrogenase AldC 689 669 ctx fusion:558
Rv1249c membrane protein 612 612 coexpression:612
Rv1189 sigI ECF RNA polymerase sigma factor SigI 576 576 ctx neighborhood:573
Rv0768 aldA aldehyde dehydrogenase AldA 579 552
Rv3063 cstA carbon starvation protein A 560 542 coexpression:542
Rv1190 hyp hypothetical protein 535 535 ctx neighborhood:532
Rv0223c aldehyde dehydrogenase 536 506
Rv3667 acs acetyl-CoAsynthetase 564 501 coexpression:488
Rv0753c mmsA methylmalonate-semialdehyde dehydrogenase 515 484
Rv1731 gabD2 succinate-semialdehyde dehydrogenase 485 451
Rv0896 gltA2 citrate synthase 1 483 429 coexpression:429

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: proline dehydrogenase
  • MTBC0 PGAP product: proline dehydrogenase
  • Pfam (hmmscan --cut_ga): Pro_dh PF01619.25 (E=2e-30)
  • (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_215704.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pro_dh (PF01619.25)
  • 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 COG0506
  • Curated reference: UniProt O50444 (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 — 28 functional partner(s); context anchor rocA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001276|Rv1188|
MAGWFAHTLRPAMLAAGRSDRLGRIVERSPLTRGVVRRFVPGDTLDDVVDIVTALRDSGRYLSIDYLGENVTDADDAAAAVRAYLGLLDVLGRRGDIACDGVRPLEVSLKLSALGQALDRDGQKIALDNARAICERAERVGAWVTVDAEDHTTTDSTLSISGDLRVDFPWLGTVVQAYLRRTLADCAELAAVGARVRLCKGAYDEPASVAYRDAAQVTDSYLRCLRVLTAGRGYPMVATHDPVIIAAVPGITRESGRSQGDFEYQMLYGVRDDEQRRLTGAGNHVRVYVPFGTRWYGYFLRRLAERPANLAFFLRALTDRRRARGCAER