fhaA Resolved · high auto-curated
H37Rv Rv0020c · MTBC0 mtbc0_000024 ·
521 aa · 23861–25426 (-) ·
RefSeq NP_214534.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | FHA domain-containing protein FhaA |
|---|---|
| MTBC0 PGAP re-annotation | cell division-associated protein FhaA |
| Revised (this work) | Cell division-associated protein FhaA. Pfam: FhaA_N (PF12401.14), Yop-YscD_cpl (PF16697.11), FHA (PF00498.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71590
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | FHA domain-containing protein FhaA |
| Curated function | Regulates cell growth and peptidoglycan synthesis by binding to MviN. May inhibit the late stages of peptidoglycan synthesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | fhaA |
| eggNOG description | Fha domain |
| Orthologous group | COG1716 |
| Gene Ontology (18) |
GO:0003674, GO:0003676, GO:0003723, GO:0003729, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0030312 +6 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 | 0.487 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 15 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 |
|---|---|---|---|---|
FhaA_N | PF12401.14 | 1.5e-34 | 9–121 | FhaA, N-terminal domain |
Yop-YscD_cpl | PF16697.11 | 3.7e-11 | 438–518 | Inner membrane component of T3SS, cytoplasmic domain |
FHA | PF00498.32 | 1.4e-18 | 450–512 | FHA domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: murJ (peptidoglycan biosynthesis protein), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3910 murJ |
peptidoglycan biosynthesis protein | 999 | 1000 ctx | cooccurence:643 experimental:999 textmining:914 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 988 | 984 | experimental:984 |
Rv0014c pknB |
serine/threonine-protein kinase PknB | 996 | 968 ctx | neighborhood:700 experimental:870 textmining:882 |
Rv0019c fhaB |
FHA domain-containing protein FhaB | 981 | 851 ctx | neighborhood:597 cooccurence:625 textmining:879 |
Rv0015c pknA |
serine/threonine-protein kinase PknA | 970 | 837 ctx | neighborhood:700 textmining:828 |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 960 | 788 ctx | neighborhood:700 textmining:823 |
Rv0016c pbpA |
penicillin-binding protein PbpA | 916 | 773 ctx | neighborhood:700 textmining:650 |
Rv0017c rodA |
cell division protein RodA | 885 | 747 ctx | neighborhood:700 textmining:564 |
Rv3212 hyp |
hypothetical protein | 748 | 736 ctx | cooccurence:731 |
Rv0556 |
transmembrane protein | 731 | 731 ctx | cooccurence:728 |
Rv2360c hyp |
hypothetical protein | 721 | 722 ctx | cooccurence:720 |
Rv1109c hyp |
hypothetical protein | 715 | 715 ctx | cooccurence:711 |
Rv0996 |
transmembrane protein | 689 | 690 ctx | cooccurence:685 |
Rv1364c |
sigma factor regulatory protein | 688 | 687 | coexpression:647 |
Rv3438 hyp |
hypothetical protein | 670 | 671 ctx | cooccurence:669 |
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: FHA domain-containing protein FhaA
- MTBC0 PGAP product: cell division-associated protein FhaA
- Pfam (hmmscan --cut_ga): FhaA_N PF12401.14 (E=1e-34), Yop-YscD_cpl PF16697.11 (E=4e-11), FHA PF00498.32 (E=1e-18)
- (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_214534.1)
- Domains: Pfam-A via hmmscan --cut_ga — FhaA_N (PF12401.14), Yop-YscD_cpl (PF16697.11), FHA (PF00498.32)
- 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
COG1716 - Curated reference: UniProt P71590 (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 —
127 functional partner(s); context anchor
murJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000024|Rv0020c|fhaA MGSQKRLVQRVERKLEQTVGDAFARIFGGSIVPQEVEALLRREAADGIQSLQGNRLLAPNEYIITLGVHDFEKLGADPELKSTGFARDLADYIQEQGWQTYGDVVVRFEQSSNLHTGQFRARGTVNPDVETHPPVIDCARPQSNHAFGAEPGVAPMSDNSSYRGGQGQGRPDEYYDDRYARPQEDPRGGPDPQGGSDPRGGYPPETGGYPPQPGYPRPRHPDQGDYPEQIGYPDQGGYPEQRGYPDQRGYQDQGRGYPDQGQGGYPPPYEQRPPVSPGPAAGYGAPGYDQGYRQSGGYGPSPGGGQPGYGGYGEYGRGPARHEEGSYVPSGPPGPPEQRPAYPDQGGYDQGYQQGATTYGRQDYGGGADYTRYTESPRVPGYAPQGGGYAEPAGRDYDYGQSGAPDYGQPAPGGYSGYGQGGYGSAGTSVTLQLDDGSGRTYQLREGSNIIGRGQDAQFRLPDTGVSRRHLEIRWDGQVALLADLNSTNGTTVNNAPVQEWQLADGDVIRLGHSEIIVRMH