htpX Resolved · high auto-curated
H37Rv Rv0563 · MTBC0 mtbc0_000592 ·
286 aa · 657430–658290 (+) ·
RefSeq NP_215077.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | protease HtpX |
|---|---|
| MTBC0 PGAP re-annotation | zinc metalloprotease HtpX |
| Revised (this work) | Zinc metalloprotease HtpX. Pfam: Peptidase_M48 (PF01435.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHS5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protease HtpX homolog |
| EC (curated) |
EC 3.4.24.-
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | htpX |
| eggNOG description | Belongs to the peptidase M48B family |
| Orthologous group | COG0501 |
| KEGG orthology |
K03799
|
| KEGG modules |
M00743
|
| Gene Ontology (13) |
GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0031224, GO:0031226, GO:0044425, GO:0044459, GO:0044464 +1 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 | 0.457 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 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 |
|---|---|---|---|---|
Peptidase_M48 | PF01435.25 | 1.0e-36 | 70–283 | Peptidase family M48 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: menJ (oxidoreductase), high confidence from genomic context alone (score 715 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2744c 35kd_ag hyp |
hypothetical protein | 821 | 822 | coexpression:816 |
Rv3837c |
phosphoglycerate mutase | 811 | 812 | coexpression:806 |
Rv0983 pepD |
serine protease PepD | 819 | 810 | coexpression:804 |
Rv2694c hyp |
hypothetical protein | 730 | 730 | coexpression:730 |
Rv0561c menJ |
oxidoreductase | 715 | 715 ctx | neighborhood:714 |
Rv0984 moaB2 |
pterin-4-alpha-carbinolamine dehydratase | 653 | 654 | coexpression:651 |
Rv0342 iniA |
isoniazid inductible protein IniA | 666 | 647 | database:643 |
Rv0562 grcC1 |
polyprenyl-diphosphate synthase GrcC | 646 | 632 ctx | neighborhood:581 |
Rv2710 sigB |
RNA polymerase sigma factor SigB | 640 | 618 | coexpression:615 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 788 | 544 | coexpression:475 textmining:555 |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 591 | 527 | |
Rv2053c fxsA |
transmembrane protein FxsA | 511 | 491 | coexpression:491 |
Rv0351 grpE |
stress response protein GrpE | 786 | 451 | coexpression:433 textmining:627 |
Rv1285 cysD |
sulfate adenylyltransferase subunit 2 | 572 | 429 | coexpression:429 |
Rv1286 cysC |
adenylyl-sulfate kinase | 416 | 416 | coexpression: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: protease HtpX
- MTBC0 PGAP product: zinc metalloprotease HtpX
- Pfam (hmmscan --cut_ga): Peptidase_M48 PF01435.25 (E=1e-36)
- (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_215077.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M48 (PF01435.25)
- 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
COG0501 - Curated reference: UniProt P9WHS5 (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 —
39 functional partner(s); context anchor
menJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000592|Rv0563|htpX MTWHPHANRLKTFLLLVGMSALIVAVGALFGRTALMLAALFAVGMNVYVYFNSDKLALRAMHAQPVSELQAPAMYRIVRELATSAHQPMPRLYISDTAAPNAFATGRNPRNAAVCCTTGILRILNERELRAVLGHELSHVYNRDILISCVAGALAAVITALANMAMWAGMFGGNRDNANPFALLLVALLGPIAATVIRMAVSRSREYQADESGAVLTGDPLALASALRKISGGVQAAPLPPEPQLASQAHLMIANPFRAGERIGSLFSTHPPIEDRIRRLEAMARG