ftsH Resolved · high auto-curated
H37Rv Rv3610c · MTBC0 mtbc0_003828 ·
760 aa · 4074305–4076587 (-) ·
RefSeq NP_218127.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | zinc metalloprotease FtsH |
|---|---|
| MTBC0 PGAP re-annotation | ATP-dependent zinc metalloprotease FtsH |
| Revised (this work) | ATP-dependent zinc metalloprotease FtsH. Pfam: FtsH_ext (PF06480.21), AAA_5 (PF07728.21), AAA (PF00004.36), AAA_lid_3 (PF17862.8), Peptidase_M41 (PF01434.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQN3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP-dependent zinc metalloprotease FtsH |
| EC (curated) |
EC 3.4.24.-
|
| Curated function | Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. Plays a role in the quality control of integral membrane proteins..; FUNCTION: Complements an E.coli null mutation. Upon overexpression in E.coli has been shown to degrade endogenous sigma-32, SecY and phage lambda cII protein. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | ftsH |
| eggNOG description | Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. Plays a role in the quality control of integral membrane proteins |
| Orthologous group | COG0465 |
| KEGG orthology |
K03798
|
| KEGG modules |
M00742
|
| Gene Ontology (48) |
GO:0003674, GO:0003824, GO:0004176, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006508, GO:0006807, GO:0006950 +36 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 | 0.195 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 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 |
|---|---|---|---|---|
FtsH_ext | PF06480.21 | 2.7e-08 | 11–105 | FtsH Extracellular |
AAA_5 | PF07728.21 | 1.7e-05 | 198–318 | AAA domain (dynein-related subfamily) |
AAA | PF00004.36 | 2.3e-47 | 199–330 | ATPase family associated with various cellular activities (AAA) |
AAA_lid_3 | PF17862.8 | 1.3e-10 | 354–394 | AAA+ lid domain |
Peptidase_M41 | PF01434.25 | 9.2e-71 | 412–601 | Peptidase family M41 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folE (GTP cyclohydrolase I), high confidence from genomic context alone (score 974 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3609c folE |
GTP cyclohydrolase I | 976 | 974 ctx | neighborhood:867 coexpression:816 |
Rv3607c folB |
dihydroneopterin aldolase | 963 | 962 ctx | neighborhood:867 coexpression:729 |
Rv1488 hyp |
hypothetical protein | 963 | 959 | coexpression:467 experimental:805 database:633 |
Rv3090 hyp |
hypothetical protein | 956 | 951 | experimental:805 database:633 |
Rv3608c folP1 |
dihydropteroate synthase | 941 | 936 ctx | neighborhood:867 coexpression:539 |
Rv2904c rplS |
50S ribosomal protein L19 | 892 | 888 | experimental:860 |
Rv3443c rplM |
50S ribosomal protein L13 | 896 | 881 | experimental:810 |
Rv3442c rpsI |
30S ribosomal protein S9 | 882 | 877 | experimental:830 |
Rv0723 rplO |
50S ribosomal protein L15 | 879 | 877 | experimental:870 |
Rv0683 rpsG |
30S ribosomal protein S7 | 875 | 875 | experimental:817 |
Rv3456c rplQ |
50S ribosomal protein L17 | 887 | 873 | experimental:830 |
Rv0701 rplC |
50S ribosomal protein L3 | 885 | 869 | experimental:817 |
Rv0704 rplB |
50S ribosomal protein L2 | 884 | 866 | experimental:810 |
Rv3459c rpsK |
30S ribosomal protein S11 | 872 | 861 | experimental:810 |
Rv0721 rpsE |
30S ribosomal protein S5 | 882 | 857 | experimental:817 |
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: zinc metalloprotease FtsH
- MTBC0 PGAP product: ATP-dependent zinc metalloprotease FtsH
- Pfam (hmmscan --cut_ga): FtsH_ext PF06480.21 (E=3e-08), AAA_5 PF07728.21 (E=2e-05), AAA PF00004.36 (E=2e-47), AAA_lid_3 PF17862.8 (E=1e-10), Peptidase_M41 PF01434.25 (E=9e-71)
- (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_218127.1)
- Domains: Pfam-A via hmmscan --cut_ga — FtsH_ext (PF06480.21), AAA_5 (PF07728.21), AAA (PF00004.36), AAA_lid_3 (PF17862.8), Peptidase_M41 (PF01434.25)
- 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
COG0465 - Curated reference: UniProt P9WQN3 (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 —
210 functional partner(s); context anchor
folE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003828|Rv3610c|ftsH MNRKNVTRTITAIAVVVLLGWSFFYFSDDTRGYKPVDTSVAITQINGDNVKSAQIDDREQQLRLILKKGNNETDGSEKVITKYPTGYAVDLFNALSAKNAKVSTVVNQGSILGELLVYVLPLLLLVGLFVMFSRMQGGARMGFGFGKSRAKQLSKDMPKTTFADVAGVDEAVEELYEIKDFLQNPSRYQALGAKIPKGVLLYGPPGTGKTLLARAVAGEAGVPFFTISGSDFVEMFVGVGASRVRDLFEQAKQNSPCIIFVDEIDAVGRQRGAGLGGGHDEREQTLNQLLVEMDGFGDRAGVILIAATNRPDILDPALLRPGRFDRQIPVSNPDLAGRRAVLRVHSKGKPMAADADLDGLAKRTVGMTGADLANVINEAALLTARENGTVITGPALEEAVDRVIGGPRRKGRIISEQEKKITAYHEGGHTLAAWAMPDIEPIYKVTILARGRTGGHAVAVPEEDKGLRTRSEMIAQLVFAMGGRAAEELVFREPTTGAVSDIEQATKIARSMVTEFGMSSKLGAVKYGSEHGDPFLGRTMGTQPDYSHEVAREIDEEVRKLIEAAHTEAWEILTEYRDVLDTLAGELLEKETLHRPELESIFADVEKRPRLTMFDDFGGRIPSDKPPIKTPGELAIERGEPWPQPVPEPAFKAAIAQATQAAEAARSDAGQTGHGANGSPAGTHRSGDRQYGSTQPDYGAPAGWHAPGWPPRSSHRPSYSGEPAPTYPGQPYPTGQADPGSDESSAEQDDEVSRTKPAHG