lepA Resolved · high auto-curated
H37Rv Rv2404c · MTBC0 mtbc0_002560 ·
653 aa · 2725534–2727495 (-) ·
RefSeq NP_216920.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GTP-binding protein LepA |
|---|---|
| MTBC0 PGAP re-annotation | translation elongation factor 4 |
| Revised (this work) | Translation elongation factor 4. Pfam: GTP_EFTU (PF00009.34), GTP_EFTU_D2 (PF03144.32), EFG_C (PF00679.31), LepA_C (PF06421.18). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK97
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Elongation factor 4 |
| EC (curated) |
EC 3.6.5.n1
|
| Curated function | Required for accurate and efficient protein synthesis under certain stress conditions. May act as a fidelity factor of the translation reaction, by catalyzing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Back-translocation proceeds from a post-translocation (POST) complex to a pre-translocation (PRE) complex, thus giving elongation factor G a second chance to translocate the tRNAs correctly. Binds to ribosomes in a GTP-dependent manner. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | lepA |
| eggNOG description | Required for accurate and efficient protein synthesis under certain stress conditions. May act as a fidelity factor of the translation reaction, by catalyzing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Back- translocation proceeds from a post-translocation (POST) complex to a pre-translocation (PRE) complex, thus giving elongation factor G a second chance to translocate the tRNAs correctly. Binds to ribosomes in a GTP-dependent manner |
| Orthologous group | COG0481 |
| KEGG orthology |
K03596
|
| KEGG pathways |
map05134
|
| Gene Ontology (11) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0030312, GO:0044424, GO:0044444, GO:0044464, GO:0071944
|
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 | 0.295 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 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 |
|---|---|---|---|---|
GTP_EFTU | PF00009.34 | 1.5e-54 | 51–229 | Elongation factor Tu GTP binding domain |
GTP_EFTU_D2 | PF03144.32 | 1.2e-08 | 252–322 | Elongation factor Tu domain 2 |
EFG_C | PF00679.31 | 6.2e-21 | 448–534 | Elongation factor G C-terminus |
LepA_C | PF06421.18 | 1.1e-48 | 538–642 | GTP-binding protein LepA C-terminus |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rplS (50S ribosomal protein L19), high confidence from genomic context alone (score 963 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2904c rplS |
50S ribosomal protein L19 | 963 | 963 ctx | cooccurence:464 experimental:917 |
Rv3443c rplM |
50S ribosomal protein L13 | 971 | 962 | experimental:919 |
Rv2890c rpsB |
30S ribosomal protein S2 | 965 | 955 | experimental:918 |
Rv2909c rpsP |
30S ribosomal protein S16 | 956 | 954 | experimental:917 |
Rv3456c rplQ |
50S ribosomal protein L17 | 956 | 953 | experimental:921 |
Rv1015c rplY |
50S ribosomal protein L25/general stress protein Ctc | 953 | 953 | coexpression:415 experimental:917 |
Rv2441c rpmA |
50S ribosomal protein L27 | 953 | 953 | experimental:917 |
Rv1643 rplT |
50S ribosomal protein L20 | 958 | 952 | experimental:917 |
Rv3442c rpsI |
30S ribosomal protein S9 | 961 | 950 | experimental:917 |
Rv2785c rpsO |
30S ribosomal protein S15 | 959 | 948 | experimental:921 |
Rv0641 rplA |
50S ribosomal protein L1 | 959 | 947 | experimental:917 |
Rv3458c rpsD |
30S ribosomal protein S4 | 956 | 944 | experimental:917 |
Rv0683 rpsG |
30S ribosomal protein S7 | 956 | 944 | experimental:920 |
Rv0053 rpsF |
30S ribosomal protein S6 | 948 | 942 | experimental:919 |
Rv0701 rplC |
50S ribosomal protein L3 | 954 | 941 | experimental:918 |
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: GTP-binding protein LepA
- MTBC0 PGAP product: translation elongation factor 4
- Pfam (hmmscan --cut_ga): GTP_EFTU PF00009.34 (E=2e-54), GTP_EFTU_D2 PF03144.32 (E=1e-08), EFG_C PF00679.31 (E=6e-21), LepA_C PF06421.18 (E=1e-48)
- (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_216920.1)
- Domains: Pfam-A via hmmscan --cut_ga — GTP_EFTU (PF00009.34), GTP_EFTU_D2 (PF03144.32), EFG_C (PF00679.31), LepA_C (PF06421.18)
- 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
COG0481 - Curated reference: UniProt P9WK97 (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 —
159 functional partner(s); context anchor
rplS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002560|Rv2404c|lepA MRTPCSQHRRDRPSAIGSQLPDADTLDTRQPPLQEIPISSFADKTFTAPAQIRNFCIIAHIDHGKSTLADRMLQLTGVVDERSMRAQYLDRMDIERERGITIKAQNVRLPWRVDKTDYVLHLIDTPGHVDFTYEVSRALEACEGAVLLVDAAQGIEAQTLANLYLALDRDLHIIPVLNKIDLPAADPDRYAAEMAHIIGCEPAEVLRVSGKTGEGVSDLLDEVVRQVPPPQGDAEAPTRAMIFDSVYDIYRGVVTYVRVVDGKISPRERIMMMSTGATHELLEVGIVSPEPKPCEGLGVGEVGYLITGVKDVRQSKVGDTVTSLSRARGAAAEALTGYREPKPMVYSGLYPVDGSDYPNLRDALDKLQLNDAALTYEPETSVALGFGFRCGFLGLLHMEITRERLEREFGLDLISTSPNVVYRVHKDDGTEIRVTNPSDWPEGKIRTVYEPVVKTTIIAPSEFIGTIMELCQSRRGELGGMDYLSPERVELRYTMPLGEIIFDFFDALKSRTRGYASLDYEEAGEQEAALVKVDILLQGEAVDAFSAIVHKDTAYAYGNKMTTKLKELIPRQQFEVPVQAAIGSKIIARENIRAIRKDVLSKCYGGDITRKRKLLEKQKEGKKRMKTIGRVEVPQEAFVAALSTDAAGDKGKK