hycD Family assigned · medium auto-curated
H37Rv Rv0084 · MTBC0 mtbc0_000094 ·
316 aa · 92491–93441 (+) ·
RefSeq NP_214598.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | formate hydrogenlyase HycD |
|---|---|
| MTBC0 PGAP re-annotation | respiratory chain complex I subunit 1 family protein |
| Revised (this work) | Respiratory chain complex I subunit 1 family protein. Pfam: NADHdh (PF00146.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
Q10881
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible formate hydrogenlyase HycD |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | hycD |
| eggNOG description | Formate hydrogenlyase |
| Orthologous group | COG0650 |
| KEGG orthology |
K12138
|
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 | 0.274 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 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 |
|---|---|---|---|---|
NADHdh | PF00146.27 | 6.9e-42 | 13–305 | NADH dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0082 (oxidoreductase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0082 |
oxidoreductase | 999 | 1000 ctx | neighborhood:882 cooccurence:768 coexpression:844 experimental:899 |
Rv0087 hycE |
formate hydrogenase HycE | 999 | 1000 ctx | neighborhood:884 cooccurence:774 coexpression:580 experimental:999 textmining:763 |
Rv0086 hycQ |
hydrogenase HycQ | 999 | 999 ctx | neighborhood:874 cooccurence:774 coexpression:801 experimental:787 |
Rv0083 |
oxidoreductase | 998 | 998 ctx | neighborhood:881 cooccurence:774 coexpression:769 experimental:787 |
Rv0085 hycP |
hydrogenase HycP | 992 | 992 ctx | neighborhood:874 cooccurence:774 coexpression:731 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 958 | 951 | coexpression:648 experimental:855 |
Rv0081 |
HTH-type transcriptional regulator | 906 | 902 ctx | neighborhood:881 |
Rv3146 nuoB |
NADH-quinone oxidoreductase subunit B | 749 | 750 | experimental:652 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 694 | 683 | experimental:652 |
Rv0088 |
polyketide cyclase/dehydrase | 657 | 657 ctx | neighborhood:644 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 638 | 593 | experimental:446 |
Rv0080 hyp |
hypothetical protein | 556 | 556 ctx | neighborhood:554 |
Rv0079 hyp |
hypothetical protein | 550 | 550 ctx | neighborhood:548 |
Rv0089 |
methyltransferase | 435 | 435 ctx | neighborhood:419 |
Rv0327c cyp135A1 |
cytochrome P450 Cyp135A1 | 518 | 47 | textmining:515 |
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: formate hydrogenlyase HycD
- MTBC0 PGAP product: respiratory chain complex I subunit 1 family protein
- Pfam (hmmscan --cut_ga): NADHdh PF00146.27 (E=7e-42)
- (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_214598.1)
- Domains: Pfam-A via hmmscan --cut_ga — NADHdh (PF00146.27)
- 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
COG0650 - Curated reference: UniProt Q10881 (TrEMBL, unreviewed; Predicted)
- 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 —
19 functional partner(s); context anchor
Rv0082 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000094|Rv0084|hycD MSYLAGAAQIGGVMVGAPLVIGMTRQVRARWEGRAGAGLLQPWRDLLKQLGKQQITPAGTTIVFAAAPVIVAGTTLLIAAIAPLVATGSPLDPSADLFAVVGLLFLGTVALTLAGIDTGTSFGGMGASREITIAALVEPTILLAVFALSIPAGSANLGALVASTIDHPGHVVSLAGVLAFVALVIVIVAETGRLPVDNPATHLELTMVHEAMVLEYAGPRLALVEWAAGMRLTVLLALLANLFLPWGIAGAAPTALDVLTGVVAVAAKVAILAVLLATFEVFLAKLRLFRVPELLAGSFLLALLAVTAANFFTVGA