Rv3575c Family assigned · medium auto-curated
H37Rv Rv3575c · MTBC0 mtbc0_003794 ·
359 aa · 4040766–4041845 (-) ·
RefSeq NP_218092.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | LacI family transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | LacI family DNA-binding transcriptional regulator |
| Revised (this work) | LacI family DNA-binding transcriptional regulator. Pfam: Peripla_BP_1 (PF00532.28), Peripla_BP_3 (PF13377.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96857
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional regulator Rv3575c |
| Curated function | Transcriptional regulator that negatively regulates transcription of the mce4 operon, which is involved in cholesterol transport and utilization. Acts by binding to the promoter region of the mce4 operon. It affects the utilization of host cholesterol as a carbon source, impacting the host's innate immune response. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Periplasmic binding protein LacI transcriptional regulator |
| Orthologous group | COG1609 |
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 | 0.078 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 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 |
|---|---|---|---|---|
Peripla_BP_1 | PF00532.28 | 1.2e-08 | 69–305 | Periplasmic binding proteins and sugar binding domain of LacI family |
Peripla_BP_3 | PF13377.13 | 8.2e-15 | 182–333 | Periplasmic binding protein-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: xylB (D-xylulose kinase XylB), medium confidence from genomic context alone (score 679 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3859c gltB |
glutamate synthase large subunit | 976 | 963 | experimental:963 |
Rv3396c guaA |
GMP synthase | 764 | 759 | experimental:757 |
Rv0729 xylB |
D-xylulose kinase XylB | 754 | 679 ctx | cooccurence:489 |
Rv3577 hyp |
hypothetical protein | 676 | 676 ctx | neighborhood:674 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 676 | 663 | experimental:650 |
Rv0186 bglS |
beta-glucosidase BglS | 591 | 566 ctx | cooccurence:551 |
Rv3576 lppH |
lipoprotein LppH | 583 | 562 ctx | neighborhood:562 |
Rv2059 hyp |
hypothetical protein | 553 | 549 ctx | neighborhood:544 |
Rv2060 |
integral membrane protein | 563 | 544 ctx | neighborhood:544 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 536 | 536 | experimental:536 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 536 | 536 | experimental:536 |
Rv0620 galK |
galactokinase | 627 | 513 | |
Rv2474c hyp |
hypothetical protein | 503 | 504 ctx | cooccurence:501 |
Rv0792c |
transcriptional regulator | 570 | 492 ctx | cooccurence:492 |
Rv2986c hupB |
DNA-binding protein HU | 507 | 451 | experimental:433 |
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: LacI family transcriptional regulator
- MTBC0 PGAP product: LacI family DNA-binding transcriptional regulator
- Pfam (hmmscan --cut_ga): Peripla_BP_1 PF00532.28 (E=1e-08), Peripla_BP_3 PF13377.13 (E=8e-15)
- (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_218092.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peripla_BP_1 (PF00532.28), Peripla_BP_3 (PF13377.13)
- 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
COG1609 - Curated reference: UniProt P96857 (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
xylB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003794|Rv3575c| MSPTPRRRATLASLAAELKVSRTTVSNAFNRPDQLSADLRERVLATAKRLGYAGPDPVARSLRTRKAGAVGLVMAEPLTYFFSDPAARDFVAGVAQSCEELGQGLQLVSVGSSRSLADGTAAVLGAGVDGFVVYSVGDDDPYLQVVLQRRLPVVVVDQPKDLSGVSRVGIDDRAAMRELAGYVLGLGHRELGLLTMRLGRDRRQDLVDAERLRSPTFDVQRERIVGVWEAMTAAGVDPDSLTVVESYEHLPTSGGTAAKVALQANPRLTALMCTADILALSAMDYLRAHGIYVPGQMTVTGFDGVPEALSRGLTTVAQPSLHKGHRAGELLLKPPRSGLPVIEVLDTELVRGRTAGPPA