35kd_ag Family assigned · medium auto-curated
H37Rv Rv2744c · MTBC0 - ·
270 aa · 3057251–3058063 (-) ·
RefSeq YP_177903.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains PspA_IM30 (PF04012.18) domain(s); putative function inferred from the domain architecture. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WHP5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PspA protein |
| Curated function | Involved in resistance to stress. Facilitates intracellular growth of M.tuberculosis. Associates with and regulates lipid droplets (LDs) homeostasis under conditions of stress and may regulate non-replicating persistence (NRP). Could be involved in preservation of envelope integrity and tolerance to surface stress. Has an inhibitory effect on ClgR activity. May block ClgR activity after stress and then, form a multiprotein complex with Rv2743c-Rv2742c, leading to the release of ClgR. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K TranscriptionT Signal transduction mechanisms
|
|---|---|
| Preferred name | pspA |
| eggNOG description | phage shock protein a (IM30), suppresses |
| Orthologous group | COG1842 |
| KEGG orthology |
K03969
|
| Gene Ontology (11) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0016020, GO:0030312, GO:0044424, 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) pseudogene candidate
| pN/pS | 2.15 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.41% of strains (2042) · clonal |
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 |
|---|---|---|---|---|
PspA_IM30 | PF04012.18 | 2.5e-55 | 3–241 | PspA/IM30 family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: clgR (transcriptional regulator ClgR), high confidence from genomic context alone (score 925 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) |
|---|---|---|---|---|
Rv2745c clgR |
transcriptional regulator ClgR | 973 | 925 ctx | neighborhood:759 coexpression:703 textmining:665 |
Rv2743c hyp |
hypothetical protein | 971 | 860 ctx | neighborhood:799 textmining:804 |
Rv0563 htpX |
protease HtpX | 821 | 822 | coexpression:816 |
Rv2710 sigB |
RNA polymerase sigma factor SigB | 834 | 808 | coexpression:801 |
Rv2468c hyp |
hypothetical protein | 810 | 807 ctx | cooccurence:738 |
Rv2179c |
3'-5' exoribonuclease | 773 | 774 ctx | cooccurence:773 |
Rv0948c |
chorismate mutase | 770 | 770 ctx | cooccurence:768 |
Rv3605c hyp |
hypothetical protein | 767 | 767 ctx | cooccurence:767 |
Rv3311 hyp |
hypothetical protein | 743 | 743 ctx | cooccurence:742 |
Rv2694c hyp |
hypothetical protein | 747 | 737 | coexpression:732 |
Rv2711 ideR |
iron-dependent repressor and activator IdeR | 740 | 731 | coexpression:731 |
Rv1209 hyp |
hypothetical protein | 729 | 725 ctx | cooccurence:719 |
Rv3412 hyp |
hypothetical protein | 714 | 714 ctx | cooccurence:710 |
Rv0049 hyp |
hypothetical protein | 704 | 705 ctx | cooccurence:703 |
Rv0813c hyp |
hypothetical protein | 695 | 695 ctx | cooccurence:692 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): PspA_IM30 PF04012.18 (E=3e-55)
- (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 YP_177903.1)
- Domains: Pfam-A via hmmscan --cut_ga — PspA_IM30 (PF04012.18)
- 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
COG1842 - Curated reference: UniProt P9WHP5 (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 —
76 functional partner(s); context anchor
clgR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2744c|35kd_ag MANPFVKAWKYLMALFSSKIDEHADPKVQIQQAIEEAQRTHQALTQQAAQVIGNQRQLEMRLNRQLADIEKLQVNVRQALTLADQATAAGDAAKATEYNNAAEAFAAQLVTAEQSVEDLKTLHDQALSAAAQAKKAVERNAMVLQQKIAERTKLLSQLEQAKMQEQVSASLRSMSELAAPGNTPSLDEVRDKIERRYANAIGSAELAESSVQGRMLEVEQAGIQMAGHSRLEQIRASMRGEALPAGGTTATPRPATETSGGAIAEQPYGQ