acrA1 Family assigned · medium auto-curated
H37Rv Rv3391 · MTBC0 mtbc0_003603 ·
650 aa · 3831060–3833012 (+) ·
RefSeq NP_217908.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA-reductase AcrA |
|---|---|
| MTBC0 PGAP re-annotation | SDR family oxidoreductase |
| Revised (this work) | SDR family oxidoreductase. Pfam: Epimerase (PF01370.28), NAD_binding_4 (PF07993.19), GDP_Man_Dehyd (PF16363.12), NAD_binding_10 (PF13460.13), 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 |
O50417
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible multi-functional enzyme with acyl-CoA-reductase activity AcrA1 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | acrA1 |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1028 |
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 | 0.414 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 10 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 |
|---|---|---|---|---|
Epimerase | PF01370.28 | 2.8e-15 | 4–170 | NAD dependent epimerase/dehydratase family |
NAD_binding_4 | PF07993.19 | 1.7e-28 | 5–218 | Male sterility protein |
GDP_Man_Dehyd | PF16363.12 | 3.4e-06 | 5–83 | GDP-mannose 4,6 dehydratase |
NAD_binding_10 | PF13460.13 | 4.2e-08 | 7–171 | NAD(P)H-binding |
adh_short | PF00106.32 | 5.0e-46 | 354–543 | short chain dehydrogenase |
KR | PF08659.17 | 1.4e-14 | 355–521 | KR domain |
adh_short_C2 | PF13561.13 | 3.8e-33 | 359–552 | Enoyl-(Acyl carrier protein) reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks13 (polyketide synthase), high confidence from genomic context alone (score 930 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 957 | 930 ctx | neighborhood:544 coexpression:838 textmining:413 |
Rv2383c mbtB |
phenyloxazoline synthase | 950 | 885 ctx | neighborhood:544 coexpression:759 textmining:590 |
Rv3480c |
diacyglycerol O-acyltransferase | 943 | 824 ctx | cooccurence:693 coexpression:419 textmining:692 |
Rv2285 |
diacylglycerol acyltransferase | 932 | 819 ctx | cooccurence:683 coexpression:420 textmining:642 |
Rv3087 |
diacyglycerol O-acyltransferase | 870 | 771 ctx | cooccurence:597 coexpression:423 textmining:458 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 880 | 763 ctx | neighborhood:544 coexpression:437 textmining:516 |
Rv3740c |
diacyglycerol O-acyltransferase | 771 | 762 ctx | cooccurence:745 |
Rv3734c tgs2 |
diacyglycerol O-acyltransferase | 941 | 759 ctx | cooccurence:745 textmining:765 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 878 | 759 ctx | neighborhood:544 coexpression:426 textmining:516 |
Rv2048c pks12 |
polyketide synthase | 878 | 759 ctx | neighborhood:544 coexpression:426 textmining:516 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 878 | 758 ctx | neighborhood:544 coexpression:425 textmining:516 |
Rv1527c pks5 |
polyketide synthase | 878 | 758 ctx | neighborhood:544 coexpression:425 textmining:516 |
Rv0895 |
diacyglycerol O-acyltransferase | 754 | 744 ctx | cooccurence:729 |
Rv2946c pks1 |
polyketide synthase | 867 | 743 ctx | neighborhood:526 coexpression:425 textmining:506 |
Rv2484c |
diacyglycerol O-acyltransferase | 888 | 737 ctx | cooccurence:539 coexpression:421 textmining:593 |
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: acyl-CoA-reductase AcrA
- MTBC0 PGAP product: SDR family oxidoreductase
- Pfam (hmmscan --cut_ga): Epimerase PF01370.28 (E=3e-15), NAD_binding_4 PF07993.19 (E=2e-28), GDP_Man_Dehyd PF16363.12 (E=3e-06), NAD_binding_10 PF13460.13 (E=4e-08), adh_short PF00106.32 (E=5e-46), KR PF08659.17 (E=1e-14), adh_short_C2 PF13561.13 (E=4e-33)
- (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_217908.1)
- Domains: Pfam-A via hmmscan --cut_ga — Epimerase (PF01370.28), NAD_binding_4 (PF07993.19), GDP_Man_Dehyd (PF16363.12), NAD_binding_10 (PF13460.13), 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 O50417 (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 —
60 functional partner(s); context anchor
pks13 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003603|Rv3391|acrA1 MRYVVTGGTGFIGRHVVSRLLDGRPEARLWALVRRQSLSRFERLAGQWGDRVRPLVGDLTELELSERTIAELGDIDHVLHCAAVHDTTWADATRAVIELAARLDATFHHVSSIAVAGDFAGHYTEADFDVGQRLPTPYHRMTFEAERLVRSTPGLRYRIYRPAVVVGDSRTGEMDTIDGPYYLFGVLAKLAVLPSFTPMLLPDIGRTNIVPVDYVADALVALMHADGRDGQTFHLTAPTAIGLRGIYRGIAGAAGLPPLLGTLPGFVAAPVLNARGRAKVLRNMAATQLGIPAEIFDVVGCAPTFTSDTTREALRGTGIHVPEFATYAPGLWRYWAEHLDPDRARRNDPLLGRHVIITGASSGIGRASAIAVAKRGATVFALARNGNALDELVTEIRAHGGQAHAFTCDVTDSASVEHTVKDILGRFDHVDYLVNNAGRSIRRSVVNSTDRLHDYERVMAVNYFGAVRMVLALLPHWRERRFGHVVNVSSAGVQARNPKYSSYLPTKAALDAFADVVASETLSDHITFTNIHMPLVATPMIVPSRRLNPVRAISAERAAAMVIRGLVEKPARIDTPLGTLAEAGNYVAPRLSRRILHQLYLGYPDSAAAQGISRPDADRPPAPRRPRRSARAGVPRPLRRLGRLVPGVHW