ephD Family assigned · medium auto-curated
H37Rv Rv2214c · MTBC0 mtbc0_002350 ·
592 aa · 2506080–2507858 (-) ·
RefSeq NP_216730.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxidoreductase EphD |
|---|---|
| MTBC0 PGAP re-annotation | SDR family oxidoreductase |
| Revised (this work) | SDR family oxidoreductase. Pfam: Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14), adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGS3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable oxidoreductase EphD |
| EC (curated) |
EC 1.-.-.-
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | ephD |
| eggNOG description | Alpha beta hydrolase |
| Orthologous group | COG1028 |
| Gene Ontology (19) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0030312, GO:0031224 +7 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 | 0.354 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 7 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 |
|---|---|---|---|---|
Abhydrolase_1 | PF00561.27 | 5.6e-44 | 30–287 | alpha/beta hydrolase fold |
Hydrolase_4 | PF12146.16 | 1.3e-07 | 31–121 | Serine aminopeptidase, S33 |
Abhydrolase_6 | PF12697.14 | 2.4e-15 | 32–293 | Alpha/beta hydrolase family |
adh_short | PF00106.32 | 3.1e-49 | 327–514 | short chain dehydrogenase |
KR | PF08659.17 | 3.9e-09 | 329–479 | KR domain |
adh_short_C2 | PF13561.13 | 4.0e-41 | 331–515 | Enoyl-(Acyl carrier protein) reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks12 (polyketide synthase), high confidence from genomic context alone (score 767 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2048c pks12 |
polyketide synthase | 832 | 767 ctx | neighborhood:514 experimental:516 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 831 | 767 ctx | neighborhood:514 experimental:516 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 860 | 766 ctx | neighborhood:514 experimental:516 textmining:428 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 831 | 766 ctx | neighborhood:514 experimental:516 |
Rv1527c pks5 |
polyketide synthase | 831 | 765 ctx | neighborhood:514 experimental:516 |
Rv3549c |
short-chain type dehydrogenase/reductase | 748 | 693 ctx | cooccurence:629 |
Rv2946c pks1 |
polyketide synthase | 723 | 637 | experimental:408 |
Rv2777c hyp |
hypothetical protein | 627 | 627 ctx | cooccurence:535 |
Rv2216 |
epimerase family protein | 595 | 595 ctx | neighborhood:547 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 639 | 583 | experimental:408 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 585 | 569 ctx | neighborhood:524 |
Rv1661 pks7 |
polyketide synthase | 591 | 527 | experimental:408 |
Rv0331 |
dehydrogenase/reductase | 532 | 493 | |
Rv1663 pks17 |
polyketide synthase | 530 | 486 | experimental:414 |
Rv1871c hyp |
hypothetical protein | 507 | 482 ctx | cooccurence:421 |
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: oxidoreductase EphD
- MTBC0 PGAP product: SDR family oxidoreductase
- Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=6e-44), Hydrolase_4 PF12146.16 (E=1e-07), Abhydrolase_6 PF12697.14 (E=2e-15), adh_short PF00106.32 (E=3e-49), KR PF08659.17 (E=4e-09), adh_short_C2 PF13561.13 (E=4e-41)
- (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_216730.1)
- Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14), adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13)
- 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
COG1028 - Curated reference: UniProt P9WGS3 (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 —
62 functional partner(s); context anchor
pks12 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002350|Rv2214c|ephD MPATQQMSRLVDSPDGVRIAVYHEGNPDGPTVVLVHGFPDSHVLWDGVVPLLAERFRIVRYDNRGVGRSSVPKPISAYTMAHFADDFDAVIGELSPGEPVHVLAHDWGSVGVWEYLRRPGASDRVASFTSVSGPSQDHLVNYVYGGLRRPWRPRTFLRAISQTLRLSYMALFSVPVVAPLLLRVALSSAAVRRNMVGDIPVDQIHHSETLARDAAHSVKTYPANYFRSFSSSRRGRAIPIVDVPVQLIVNSQDPYVRPYGYDQTARWVPRLWRRDIKAGHFSPMSHPQVMAAAVHDFADLADGKQPSRALLRAQVGRPRGYFGDTLVSVTGAGSGIGRETALAFAREGAEIVISDIDEATVKDTAAEIAARGGIAYPYVLDVSDAEAVEAFAERVSAEHGVPDIVVNNAGIGQAGRFLDTPAEQFDRVLAVNLGGVVNGCRAFGQRLVERGTGGHIVNVSSMAAYAPLQSLSAYCTSKAATYMFSDCLRAELDAAGVGLTTICPGVIDTNIVATTGFHAPGTDEEKIDGRRGQIDKMFALRSYGPDKVADAIVSAVKKKKPIRPVAPEAYALYGISRVLPQALRSTARLRVI