mku Resolved · high auto-curated
H37Rv Rv0937c · MTBC0 mtbc0_000995 ·
273 aa · 1048416–1049237 (-) ·
RefSeq NP_215452.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | non-homologous end joining protein Ku |
|---|---|
| MTBC0 PGAP re-annotation | Ku protein |
| Revised (this work) | Ku protein. Pfam: Ku (PF02735.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKD9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Non-homologous end joining protein Ku |
| Curated function | With LigD forms a non-homologous end joining (NHEJ) repair enzyme. Binds linear dsDNA with 5'- and 3'-overhangs but not closed circular dsDNA nor ssDNA. One dimer binds for every 30 bp. Recruits and stimulates the ligase activity of LigD but not of T4 ligase or a human ligase complex (LIG4/XRCC4). Attenuates the 3'- to 5'-exonuclease activity of LigD. Stimulates the template-directed addition of dNTPs by LigD on 5'-overhangs and nuclease activity on 3'-overhangs. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | ku |
| eggNOG description | With LigD forms a non-homologous end joining (NHEJ) DNA repair enzyme, which repairs dsDNA breaks with reduced fidelity. Binds linear dsDNA with 5'- and 3'- overhangs but not closed circular dsDNA nor ssDNA. Recruits and stimulates the ligase activity of LigD |
| Orthologous group | COG1273 |
| KEGG orthology |
K10979
|
| KEGG pathways |
map03450
|
| Gene Ontology (39) |
GO:0000726, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0005488, GO:0006139, GO:0006259, GO:0006281, GO:0006302, GO:0006303, GO:0006725 +27 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 | 0.176 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 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 |
|---|---|---|---|---|
Ku | PF02735.23 | 4.9e-53 | 11–194 | Ku70/Ku80 beta-barrel domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ligD (multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD), high confidence from genomic context alone (score 954 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD | 997 | 954 ctx | neighborhood:628 cooccurence:774 coexpression:501 textmining:956 |
Rv3730c ligD hyp |
hypothetical protein | 927 | 864 ctx | cooccurence:773 coexpression:404 textmining:489 |
Rv0269c hyp |
hypothetical protein | 898 | 864 ctx | cooccurence:773 coexpression:402 |
Rv3731 ligC |
DNA ligase C | 983 | 840 ctx | cooccurence:765 textmining:901 |
Rv0949 uvrD1 |
ATP-dependent DNA helicase UvrD | 876 | 722 | database:720 textmining:575 |
Rv3062 ligB |
DNA ligase | 889 | 674 ctx | cooccurence:578 textmining:674 |
Rv0939 |
bifunctional 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase | 597 | 597 ctx | neighborhood:591 |
Rv3198c uvrD2 |
ATP-dependent DNA helicase UvrD | 669 | 543 | database:540 |
Rv3202c adnA |
ATP-dependent DNA helicase | 568 | 541 | database:540 |
Rv3201c adnB |
ATP-dependent DNA helicase | 568 | 541 | database:540 |
Rv2737c recA |
recombinase A | 603 | 44 | textmining:603 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta | 493 | 44 | textmining:492 |
Rv3014c ligA |
DNA ligase A | 415 | 41 | textmining:416 |
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: non-homologous end joining protein Ku
- MTBC0 PGAP product: Ku protein
- Pfam (hmmscan --cut_ga): Ku PF02735.23 (E=5e-53)
- (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_215452.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ku (PF02735.23)
- 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
COG1273 - Curated reference: UniProt P9WKD9 (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 —
13 functional partner(s); context anchor
ligD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000995|Rv0937c|mku MRAIWTGSIAFGLVNVPVKVYSATADHDIRFHQVHAKDNGRIRYKRVCEACGEVVDYRDLARAYESGDGQMVAITDDDIASLPEERSREIEVLEFVPAADVDPMMFDRSYFLEPDSKSSKSYVLLAKTLAETDRMAIVHFTLRNKTRLAALRVKDFGKREVMMVHTLLWPDEIRDPDFPVLDQKVEIKPAELKMAGQVVDSMADDFNPDRYHDTYQEQLQELIDTKLEGGQAFTAEDQPRLLDEPEDVSDLLAKLEASVKARSKANSNVPTPP