htrA Resolved · high auto-curated
H37Rv Rv1223 · MTBC0 - ·
528 aa · 1365875–1367461 (+) ·
RefSeq NP_215739.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine protease HtrA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Serine protease HtrA. Pfam: Trypsin (PF00089.33), Trypsin_2 (PF13365.13), PDZ_2 (PF13180.13), PDZ (PF00595.30), PDZ_6 (PF17820.8). |
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 |
O06291
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable serine protease HtrA1 |
| EC (curated) |
EC 3.4.21.107
|
| Curated function | Essential protein that may act as a regulatory protease that is conditionally activated upon appropriate environmental triggers. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | htrA |
| eggNOG description | serine protease |
| Orthologous group | COG0265 |
| KEGG orthology |
K08372
|
| KEGG pathways |
map02020
|
| Gene Ontology (244) |
GO:0000785, GO:0001101, GO:0003674, GO:0003824, GO:0004175, GO:0004252, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005634 +232 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 | 0.959 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 11 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.16% of strains (234) · 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 |
|---|---|---|---|---|
Trypsin | PF00089.33 | 3.1e-18 | 251–424 | Trypsin |
Trypsin_2 | PF13365.13 | 9.0e-36 | 254–401 | Trypsin-like peptidase domain |
PDZ_2 | PF13180.13 | 4.9e-14 | 440–522 | PDZ domain |
PDZ | PF00595.30 | 4.3e-06 | 441–489 | PDZ domain |
PDZ_6 | PF17820.8 | 3.6e-06 | 459–493 | PDZ domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tatB (Sec-independent protein translocase protein TatB), high confidence from genomic context alone (score 966 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1224 tatB |
Sec-independent protein translocase protein TatB | 967 | 966 ctx | neighborhood:881 coexpression:730 |
Rv2115c mpa |
proteasome-associated ATPase | 831 | 820 | experimental:551 database:594 |
Rv1222 rseA |
anti-sigma E factor RseA | 776 | 773 ctx | neighborhood:659 |
Rv3696c glpK |
glycerol kinase | 766 | 752 | experimental:402 database:589 |
Rv1334 mec |
[CysO | 719 | 709 | database:576 |
Rv2110c prcB |
proteasome subunit beta | 691 | 628 | database:562 |
Rv2109c prcA |
proteasome subunit alpha | 645 | 628 | database:562 |
Rv2555c alaS |
alanine--tRNA ligase | 640 | 628 | database:586 |
Rv0118c oxcA |
oxalyl-CoA decarboxylase OxcA | 619 | 620 | database:529 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 654 | 609 | |
Rv2609c |
membrane protein | 617 | 608 | database:530 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 649 | 603 | |
Rv2048c pks12 |
polyketide synthase | 647 | 601 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 647 | 600 | |
Rv1527c pks5 |
polyketide synthase | 646 | 599 |
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): serine protease HtrA
- Pfam (hmmscan --cut_ga): Trypsin PF00089.33 (E=3e-18), Trypsin_2 PF13365.13 (E=9e-36), PDZ_2 PF13180.13 (E=5e-14), PDZ PF00595.30 (E=4e-06), PDZ_6 PF17820.8 (E=4e-06)
- (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_215739.2)
- Domains: Pfam-A via hmmscan --cut_ga — Trypsin (PF00089.33), Trypsin_2 (PF13365.13), PDZ_2 (PF13180.13), PDZ (PF00595.30), PDZ_6 (PF17820.8)
- 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
COG0265 - Curated reference: UniProt O06291 (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 —
235 functional partner(s); context anchor
tatB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1223|htrA MDTRVDTDNAMPARFSAQIQNEDEVTSDQGNNGGPNGGGRLAPRPVFRPPVDPASRQAFGRPSGVQGSFVAERVRPQKYQDQSDFTPNDQLADPVLQEAFGRPFAGAESLQRHPIDAGALAAEKDGAGPDEPDDPWRDPAAAAALGTPALAAPAPHGALAGSGKLGVRDVLFGGKVSYLALGILVAIALVIGGIGGVIGRKTAEVVDAFTTSKVTLSTTGNAQEPAGRFTKVAAAVADSVVTIESVSDQEGMQGSGVIVDGRGYIVTNNHVISEAANNPSQFKTTVVFNDGKEVPANLVGRDPKTDLAVLKVDNVDNLTVARLGDSSKVRVGDEVLAVGAPLGLRSTVTQGIVSALHRPVPLSGEGSDTDTVIDAIQTDASINHGNSGGPLIDMDAQVIGINTAGKSLSDSASGLGFAIPVNEMKLVANSLIKDGKIVHPTLGISTRSVSNAIASGAQVANVKAGSPAQKGGILENDVIVKVGNRAVADSDEFVVAVRQLAIGQDAPIEVVREGRHVTLTVKPDPDST