Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | DNA polymerase domain-containing protein |
|---|
| Revised (this work) | LigD-type primase-polymerase (Pfam LigD_Prim-Pol PF21686 + DNA_primase_S PF01896): the polymerase/primase (PolDom) module of the bacterial non-homologous end-joining (NHEJ) DNA double-strand-break repair pathway. |
|---|
Curated reference (UniProt)
| UniProt |
P95226
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | DNA ligase D polymerase domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|
| eggNOG description | DNA primase |
|---|
| Orthologous group | COG3285 |
|---|
| EC number |
EC 6.5.1.1
|
|---|
| KEGG orthology |
K01971
|
|---|
| KEGG pathways |
map03450
|
|---|
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 |
0.227 · 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 |
|---|
LigD_Prim-Pol | PF21686.4 |
5.4e-87 | 37–288 |
LigD, primase-polymerase domain |
DNA_primase_S | PF01896.26 |
4.5e-10 | 141–261 |
DNA primase small subunit |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
ligC (DNA ligase C),
high confidence from genomic context alone
(score 975 excluding text-mining).
This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3731 ligC |
DNA ligase C |
981 |
975 ctx |
fusion:878 cooccurence:773 |
Rv0937c mku |
non-homologous end joining protein Ku |
898 |
864 ctx |
cooccurence:773 coexpression:402 |
Rv3062 ligB |
DNA ligase |
769 |
648 ctx |
cooccurence:635 |
Rv0268c hyp |
hypothetical protein |
941 |
597 ctx |
neighborhood:596 textmining:860 |
Rv0270 fadD2 |
fatty-acid--CoA ligase FadD2 |
582 |
582 ctx |
neighborhood:578 |
Rv0265c |
iron ABC transporter substrate-binding lipoprotein |
546 |
546 ctx |
neighborhood:544 |
Rv0264c hyp |
hypothetical protein |
531 |
532 ctx |
neighborhood:529 |
Rv2828A hyp |
hypothetical protein |
465 |
465 ctx |
cooccurence:464 |
Rv3296 lhr |
ATP-dependent helicase |
428 |
429 ctx |
cooccurence:427 |
Rv0263c hyp |
hypothetical protein |
402 |
402 |
|
Rv3662c hyp |
hypothetical protein |
439 |
47 |
textmining:436 |
Rv2515c hyp |
hypothetical protein |
804 |
46 |
textmining:803 |
Rv2514c hyp |
hypothetical protein |
810 |
44 |
textmining:810 |
Rv0367c hyp |
hypothetical protein |
803 |
44 |
textmining:803 |
Rv3641c fic |
cell filamentation protein Fic |
869 |
41 |
textmining:869 |
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
- MTBC0 PGAP product: 'DNA polymerase domain-containing protein'
- Pfam: LigD_Prim-Pol PF21686 (E=5.4e-87), DNA_primase_S PF01896 (E=4.5e-10) -- NHEJ primase-polymerase
ESM Atlas signal (exploratory)
Ancestral protein hash d569b388ded406dafb90cbaa5d2d4c7f.
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 12053 |
1.35 |
C-terminal nucleic acid-binding domains |
| 2 | 5369 |
1.14 |
Acidic/polar IDRs and surfaces |
| 3 | 4341 |
1.12 |
Extracytoplasmic C-termini and motif peaks |
| 4 | 3641 |
1.05 |
ssDNA primases and HUH enzymes |
| 5 | 13995 |
1.05 |
Cofactor-positioning active-site lid |
| 6 | 10095 |
1.03 |
Solvent-exposed beta-strand motif |
| 7 | 9827 |
0.83 |
Nucleotide-engaging catalytic helices |
| 8 | 14829 |
0.80 |
Intein-HE and PrimPol activation |
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_214783.1)
- Domains: Pfam-A via hmmscan --cut_ga — LigD_Prim-Pol (PF21686.4), DNA_primase_S (PF01896.26)
- 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
COG3285
- Curated reference: UniProt
P95226
(TrEMBL, unreviewed; 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 —
25 functional partner(s); context anchor
ligC
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000286|Rv0269c|
MSRMAAPVSLDVHGRQVIVTHPGRVVFPAHNDRKGYTKFDLVRYYLAVAEGAMRGVAGRPMILKRFVKGISAEAVFQKRAPANRPDWVDVAELHYASGRSAAEAVIHDAAGLAWVINLGCVDLNPHPVLAGDLDHPDELRVDLDPMPGVAWQRVVEVALVVREVLEDYGLTAWPKTSGSRGFHVYARIAPCWSFPQVRLAAQTVAREVERRLPDAATSRWWKEEREGVFVDFNQNAKDRTVASAYSVRATPDARVSTPLHWEEVPGCDPAVFTMATVPSRLADIGDPWAGMDDAVGRLDRLLMLAEELGPPQKAQSAKPLIEIARAKTRAEAMAALDIWRDRYPGAAALLRPADVLVDGMRGPSSIWYRIRINLQHVPADQRPPQEELIADYSPWPR
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