crp Family assigned · medium auto-curated
H37Rv Rv3676 · MTBC0 mtbc0_003895 ·
224 aa · 4140308–4140982 (+) ·
RefSeq NP_218193.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cAMP receptor protein |
|---|---|
| MTBC0 PGAP re-annotation | cAMP-activated global transcriptional regulator CRP |
| Revised (this work) | CAMP-activated global transcriptional regulator CRP. Pfam: cNMP_binding (PF00027.36), HTH_Crp_2 (PF13545.13), Crp (PF00325.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMH3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CRP-like cAMP-activated global transcriptional regulator |
| Curated function | Global transcriptional regulator that complexes with cAMP and binds to specific DNA promoter sites, causing DNA-bending, to regulate transcription. cAMP improves binding to specific DNA sequences, probably by altering protein conformation. The CRP regulon is predicted to contain about 115 genes. Some genes are activated by CRP (rpfA, whiB1) while others are repressed (fadD10). There are 2 CRP-binding sites in the promoter of whiB1, at low concentrations of CRP with or without cAMP transcription of whiB1 is enhanced via site CRP1, then repressed as site CRP2 is filled. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | glxR |
| eggNOG description | COG0664 cAMP-binding proteins - catabolite gene activator and regulatory subunit of cAMP-dependent protein kinases |
| Orthologous group | COG0664 |
| KEGG orthology |
K10914
|
| KEGG pathways |
map02020, map02024, map02025, map02026, map05111
|
| Gene Ontology (96) |
GO:0000166, GO:0000976, GO:0001067, GO:0001130, GO:0001216, GO:0001217, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488 +84 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 | 1.072 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 |
|---|---|---|---|---|
cNMP_binding | PF00027.36 | 2.7e-25 | 29–114 | Cyclic nucleotide-binding domain |
HTH_Crp_2 | PF13545.13 | 4.9e-18 | 148–221 | Crp-like helix-turn-helix domain |
Crp | PF00325.27 | 6.4e-05 | 175–204 | Bacterial regulatory proteins, crp family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: marP (serine protease), medium confidence from genomic context alone (score 665 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3671c marP |
serine protease | 691 | 665 ctx | neighborhood:655 |
Rv2239c hyp |
hypothetical protein | 650 | 650 ctx | cooccurence:645 |
Rv3645 |
transmembrane protein | 725 | 621 | |
Rv1339 hyp |
hypothetical protein | 655 | 615 ctx | cooccurence:601 |
Rv2212 |
adenylyl cyclase | 753 | 610 | |
Rv1625c cya |
adenylate cyclase | 784 | 594 | textmining:491 |
Rv2435c |
cyclase | 772 | 594 | experimental:408 textmining:464 |
Rv3675 |
membrane protein | 585 | 585 ctx | neighborhood:580 |
Rv3674c nth |
endonuclease III | 577 | 577 ctx | neighborhood:486 |
Rv2488c |
LuxR family transcriptional regulator | 657 | 562 | experimental:440 |
Rv1358 |
transcriptional regulator | 621 | 560 | experimental:440 |
Rv0386 |
transcriptional regulator | 583 | 557 | experimental:440 |
Rv1320c |
adenylate cyclase | 746 | 543 | textmining:469 |
Rv3457c rpoA |
DNA-directed RNA polymerase subunit alpha | 524 | 525 | experimental:447 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 567 | 520 | database:431 |
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: cAMP receptor protein
- MTBC0 PGAP product: cAMP-activated global transcriptional regulator CRP
- Pfam (hmmscan --cut_ga): cNMP_binding PF00027.36 (E=3e-25), HTH_Crp_2 PF13545.13 (E=5e-18), Crp PF00325.27 (E=6e-05)
- (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_218193.1)
- Domains: Pfam-A via hmmscan --cut_ga — cNMP_binding (PF00027.36), HTH_Crp_2 (PF13545.13), Crp (PF00325.27)
- 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
COG0664 - Curated reference: UniProt P9WMH3 (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 —
103 functional partner(s); context anchor
marP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003895|Rv3676|crp MDEILARAGIFQGVEPSAIAALTKQLQPVDFPRGHTVFAEGEPGDRLYIIISGKVKIGRRAPDGRENLLTIMGPSDMFGELSIFDPGPRTSSATTITEVRAVSMDRDALRSWIADRPEISEQLLRVLARRLRRTNNNLADLIFTDVPGRVAKQLLQLAQRFGTQEGGALRVTHDLTQEEIAQLVGASRETVNKALADFAHRGWIRLEGKSVLISDSERLARRAR