Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenosylhomocysteinase |
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| MTBC0 PGAP re-annotation | adenosylhomocysteinase |
|---|
| Revised (this work) | Adenosylhomocysteinase. Pfam: AdoHcyase (PF05221.24), AdoHcyase_NAD (PF00670.28), 2-Hacid_dh_C (PF02826.26), KARI_N (PF07991.19). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGV3
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Adenosylhomocysteinase |
|---|
| EC (curated) |
EC 3.13.2.1
|
|---|
| Curated function | May play a key role in the regulation of the intracellular concentration of adenosylhomocysteine. |
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Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
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| Preferred name | ahcY |
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| eggNOG description | May play a key role in the regulation of the intracellular concentration of adenosylhomocysteine |
|---|
| Orthologous group | COG0499 |
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| EC number |
EC 3.3.1.1
|
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| KEGG orthology |
K01251
|
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| KEGG pathways |
map00270, map01100
|
|---|
| KEGG modules |
M00035
|
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| Gene Ontology (103) |
GO:0000096, GO:0000098, GO:0000166, GO:0003674, GO:0003824, GO:0004013, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005622 +91 more
|
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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 |
0.187 · strong purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 3 missense, 0 nonsense, 0 frameshift
|
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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 |
|---|
AdoHcyase | PF05221.24 |
1.2e-148 | 20–494 |
S-adenosyl-L-homocysteine hydrolase |
AdoHcyase_NAD | PF00670.28 |
9.1e-78 | 253–415 |
S-adenosyl-L-homocysteine hydrolase, NAD binding domain |
2-Hacid_dh_C | PF02826.26 |
3.3e-09 | 273–362 |
D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain |
KARI_N | PF07991.19 |
2.5e-07 | 273–338 |
Acetohydroxy acid isomeroreductase, NADPH-binding domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase |
958 |
953 |
coexpression:526 database:900 |
Rv2124c metH |
methionine synthase |
971 |
940 |
database:900 textmining:554 |
Rv1077 cbs |
cystathionine beta-synthase |
941 |
934 |
database:900 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase |
950 |
918 |
database:900 textmining:428 |
Rv1079 metB |
cystathionine gamma-synthase |
929 |
917 |
database:900 |
Rv0091 mtn |
5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase |
909 |
904 |
database:900 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase |
916 |
901 |
database:900 |
Rv2294 |
cystathionine beta-lyase |
900 |
901 |
database:900 |
Rv0075 |
aminotransferase |
900 |
901 |
database:900 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM |
902 |
900 |
database:900 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase |
858 |
847 |
database:800 |
Rv3684 |
lyase |
857 |
843 |
database:800 |
Rv1294 thrA |
homoserine dehydrogenase |
841 |
835 |
database:800 |
Rv3238c mddA |
integral membrane protein |
822 |
823 |
database:800 |
Rv1559 ilvA |
threonine dehydratase IlvA |
836 |
813 |
database:800 |
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: adenosylhomocysteinase
- MTBC0 PGAP product: adenosylhomocysteinase
- Pfam (hmmscan --cut_ga): AdoHcyase PF05221.24 (E=1e-148), AdoHcyase_NAD PF00670.28 (E=9e-78), 2-Hacid_dh_C PF02826.26 (E=3e-09), KARI_N PF07991.19 (E=2e-07)
- (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_217765.1)
- Domains: Pfam-A via hmmscan --cut_ga — AdoHcyase (PF05221.24), AdoHcyase_NAD (PF00670.28), 2-Hacid_dh_C (PF02826.26), KARI_N (PF07991.19)
- 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
COG0499
- Curated reference: UniProt
P9WGV3
(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 —
101 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003456|Rv3248c|sahH
MTGNLVTKNSLTPDVRNGIDFKIADLSLADFGRKELRIAEHEMPGLMSLRREYAEVQPLKGARISGSLHMTVQTAVLIETLTALGAEVRWASCNIFSTQDHAAAAVVVGPHGTPDEPKGVPVFAWKGETLEEYWWAAEQMLTWPDPDKPANMILDDGGDATMLVLRGMQYEKAGVVPPAEEDDPAEWKVFLNLLRTRFETDKDKWTKIAESVKGVTEETTTGVLRLYQFAAAGDLAFPAINVNDSVTKSKFDNKYGTRHSLIDGINRGTDALIGGKKVLICGYGDVGKGCAEAMKGQGARVSVTEIDPINALQAMMEGFDVVTVEEAIGDADIVVTATGNKDIIMLEHIKAMKDHAILGNIGHFDNEIDMAGLERSGATRVNVKPQVDLWTFGDTGRSIIVLSEGRLLNLGNATGHPSFVMSNSFANQTIAQIELWTKNDEYDNEVYRLPKHLDEKVARIHVEALGGHLTKLTKEQAEYLGVDVEGPYKPDHYRY
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