chp1 Resolved · high auto-curated

Annotation: from legacy to revised

Curation note: P16.23 (phase135, 2026-08-17): couche tss ajoutee (leaderless=False). P49.1 (phase233, 2026-09-15): couche tss re-clee (leaderless=False).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

In the literature (TB corpus sweep) 1 publication

Found under: H37Rv (1).

1 TB publication mentions this gene. 1 publication(s) mention this gene (title/abstract), verified against the text. The atlas states the function; these are the primary sources that discuss it.

This layer CITES the literature, it does not change the verdict or the function. A gene may be heavily studied (as an antigen, a resistance determinant, a drug target) while its molecular function is settled elsewhere in the fiche. This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: PubMed (whole), MULTI-ALIAS sweep: H37Rv locus tag AND every ortholog identifier (M. bovis Mb…, M. marinum MMAR_…, M. smegmatis MSMEG_…, M. leprae ML…, M. abscessus MAB_…), each hit VERIFIED against the abstract text (word-boundary regex). phase73/phase75, 2026-07-13.

Intrinsic disorder (sequence + structure) highly disordered

sequence-based disorder is high but AlphaFold folds it confidently (pLDDT>=70): treat the disorder call with caution (possible metapredict over-call)

A property (biophysics), not a function. No LLPS/condensate claim is made from disorder alone. Verdict unchanged. Source: metapredict v3 (Emenecker/Holehouse) per-residue disorder + AlphaFold mean pLDDT (annotation_mtbc P16.13).

Phenotype-driven functional lead (hypothesis) priority 2.4

required for fitness in vivo (virulence / persistence factor); predicted secreted (signal peptide).

This locus is a "hypothetical" with a conditional Tn-seq phenotype. The statement above is a working hypothesis for its functional context, synthesised from the phenotype pattern and the corroborating layers on this page (conservation, STRING coupling, operon, regulon, localisation, structure) — a prioritised requalification candidate to validate, not an established function.

Conditional expression context (iModulons)

Member of 1 independently-modulated gene set(s): PhoP (phoP).

iModulon membership (independently-modulated gene sets from a 647-sample RNA-seq compendium): the conditional co-expression context. Co-expression is a regulatory context, NOT a molecular function. Source: iModulonDB / modulome_mtb (Yoo 2022).

Transcriptional start site (informative, coordinates unchanged)

Primary TSS at position 4286347 (+ strand), 491 bp 5'UTR. TSS-derived candidate start codon: 4286838 (60 bp from the annotated start) -- candidate only, not applied to this record's coordinates.

Genome-wide 5'-triphosphate-enriched RNA-seq TSS mapping (Cortes et al. 2013): informative context on transcript architecture only. reannotated_start_candidate is the authors' TSS-derived candidate start codon -- reported for information, NEVER applied to this atlas's start_mtbc0/end_mtbc0 coordinates (P19 MTBC0<->H37Rv anchoring). Row re-keyed to this locus by matching its genomic boundary against the H37Rv GFF3 (P49.1 (phase233, 2026-09-15), P49): the original ingestion (P16.23/phase135, 2026-08-17) trusted the source table's own gene-identity column, which was desynchronised from its own numeric columns on 547/651 checkable rows -- see P49 for the full diagnostic. A missing primary_tss here means this gene falls outside the 680-gene re-annotation-candidate subset the source table covers, not an absence of transcription. Source: Cortes et al. 2013 (Cell Reports), Table S3 (TSS mapping and re-annotation of start codons), 680-gene re-annotation-candidate subset of >4,000 genome-wide TSS -- row re-keyed to this locus by coordinate match (P49).

CRISPRi vulnerability

Vulnerability index 1.27 (95% CI -0.62 to 4.24). A more negative index = more vulnerable to knockdown (better drug-target quality); indicative threshold VI ≤ -6 = highly vulnerable.

Quantitative CRISPRi knockdown, graded (finer than binary Tn-seq essentiality). Source: CRISPRi vulnerability index (Bosch 2021, supplementary Table S2 'mmc3.xlsx', bulk import via Europe PMC -- supersedes the per-gene pebble.rockefeller.edu scrape of phase46_crispri_vulnerability.py).

Caveat on this estimate. Bosch et al. flag this gene's vulnerability estimate as NOT certain, and here that call has a mechanical cause visible in the library itself: every guide targeting this gene is >=21 nt (str_span=0.279 on a 0-1 scale, near the genome floor), and guide repression strength saturates from 21 nt on -- so the library never sampled a partial knockdown for this gene, only the near-maximal repression plateau. The dose-response fit (and this VI) is therefore essentially unconstrained by data, not merely uncertain -- a limitation of the CRISPRi library design for the non-essential class (Bosch et al. 2021), not a defect in this specific measurement. n_guides=8 is descriptive only and does not predict this. Do not cite this VI as a standalone vulnerability claim.

Legacy record & comparison (Mycobrowser) ahead of Mycobrowser

Mycobrowser classes this locus among conserved hypotheticals; the atlas now assigns a functional handle (curated function (UniProt), EC number, COG category, requalified function). Mycobrowser is no longer maintained, so its EC numbers predate recent nomenclature revisions (e.g. the 2018 EC 7 "translocase" class) — most EC differences are re-numberings of the same enzyme, not conflicts.

Orthologues (reciprocal best hits across mycobacteria)

Reciprocal-best-hit orthologues (DIAMOND) against the Mycobrowser reference proteomes. A missing species is informative: e.g. a gene absent from M. leprae was likely lost in its reductive genome evolution. Locus tags link to Mycobrowser.

Curated reference (UniProt)

Functional vocabulary (eggNOG-mapper, orthology transfer)

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, 142 601 strains, snapshot of 2026-09-29) pseudogene candidate

Read the disruption percentage against its ceiling, not against 100%. The strain collection is deeply imbalanced by clade, so a loss fixed in an entire lineage still shows a small overall fraction: a gene disrupted in every L6 strain caps at 0.96% of the collection, in every M. caprae strain at 0.20%, in every M. microti strain at 0.02%. Of the 705 clades in this collection, 689 have a ceiling below 1%. A figure of "0.15% of strains" is therefore uninterpretable on its own — it can be noise or a complete, lineage-defining loss. Use the clade attribution row above, which gives the sub-clade sizes, and never read the percentage alone.

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.

Outgroup conservation (beyond the MTBC) Mycobacteriaceae

Two orthogonal outgroup signals. M. canettii (the immediate outgroup) gives a deep-divergence dN/dS (a low value confirms a constrained, real gene; shown as confident only at ≥8 substitutions, else flagged low-power). Genus-wide presence/absence (tblastn vs assembled non-MTBC genomes) places the gene on the ancient-core ↔ MTBC-specific axis: a gene absent even from the closest MTBAP relatives is a candidate MTBC-specific innovation (possible host-adaptation factor, to confirm by synteny). The phylostratum extends that axis outside the genus (tblastn vs 13 reference genomes spanning Mycobacteriaceae → Corynebacteriales → Actinomycetia → outside the phylum): it is the deepest clade in which a homolog is still detected, i.e. a proxy for gene age. Read it with the null model in mind: a shallow (young) stratum can also reflect homology-detection failure for short or fast-evolving ORFs, so it is a descriptive axis, not a proof of novelty.

Essentiality (transposon mutagenesis)

Genome-wide Himar1 transposon essentiality in H37Rv (DeJesus 2017). An essential call (ES/ESD/GD) is strong, independent evidence that a "hypothetical" locus encodes a functional, selectively required gene — orthogonal to intra-species conservation.

Mutant phenotypes (conditional Tn-seq, MtbTnDB) in-vivo phenotype

Conditional fitness of transposon-disruption mutants across 3 significant condition(s) (|log2FC|≥1, q≤0.05), from the standardized MtbTnDB compendium. A negative log2FC means the mutant is depleted — the gene contributes to fitness in that condition. An in-vivo defect for a "hypothetical" is strong evidence it matters for infection, even without a known molecular function. Disruption (Tn insertion), not a clean deletion; genetic-interaction screens excluded.

Provenance note on a condition above. MtbTnDB labels this condition in vivo (Collaborative Cross mouse panel) and attributes it to Smith et al. 2022, eLife 74419. Both are wrong and for the same reason: its left arm, `mbio_H37Rv`, is the saturated H37Rv reference of DeJesus et al. 2017 (mBio 8(1):e02133-16, fourteen independent Tn libraries grown in standard medium), not a mouse strain, and the upstream generator read the token before `_vs_` as a mouse-strain name. The same sample is the in vitro control of six knockout screens in the same file. Measured here on rank correlation over 3971 genes: this condition tracks the other 81 first-order in vivo conditions at rho = +0.03, where those conditions track each other at +0.270 -- it does not behave like an infection measurement. What the comparison actually is could not be established, so it is reported as undetermined rather than renamed, and it is excluded from the in vivo count of this fiche.

Proteomics (mass spectrometry) detected

Detection by mass spectrometry is direct, experimental evidence that the protein product exists — orthogonal to sequence conservation and to Tn-seq essentiality, and especially decisive for a "hypothetical" locus. Read the dataset count as abundance, not as replication. Measured across this atlas (3,491 detected proteins), the number of datasets a protein appears in tracks its abundance almost monotonically: median 1.2 ppm at 1 dataset of 16, 27 ppm at 10, 392 ppm at 15, 1,325 ppm at 16 — three orders of magnitude. A high count therefore says the protein is abundant more than it says several independent experiments confirmed it. For most detected proteins, what the count does establish, at any value, is that the product exists. This locus belongs to the PE/PPE family, whose long, low-complexity repeat domains carry few tryptic peptides usable for MS identification: median 5 peptides (7–30 aa, in-silico trypsin digest) per detected PE/PPE protein in this atlas, against 13 for the rest of the detected proteome (Mann-Whitney p < 10^-30, n=103 vs n=3,388). A detection here can therefore rest on very few peptides: the existence claim still holds, but it is weaker than the same count would be outside this family.

Predicted localisation (DeepTMHMM + lipobox) signal peptide

Transmembrane topology and signal peptide from DeepTMHMM (deep-learning reference predictor); lipoproteins from a (myco)bacterial lipobox motif. A sequence-based prediction of subcellular context.

Physico-chemical properties (computed, ProtParam)

Computed from the ancestral MTBC0 sequence with the ExPASy ProtParam method (Biopython). Descriptive biophysical context: a positive GRAVY flags a hydrophobic (often membrane) protein, a high instability index (>40) predicts a short in-vitro half-life, an extreme pI hints at compartment or binding partner.

Domains (Pfam, hmmscan --cut_ga)

3D structure (interactive — Mol*/pdbe-molstar)

No experimental structure is deposited for this gene: showing the AlphaFold DB predicted model (mean pLDDT 72.1, confident), coloured by per-residue confidence (dark blue = very high, orange/red = low — treat low-confidence regions as unreliable, especially termini and loops). Drag to rotate, scroll to zoom.

Genomic context (neighbours & predicted operon) operon of 2

Neighbours from the H37Rv annotation (+ strand). The operon is predicted by co-directional intergenic distance (same strand, gaps ≤50 bp) — a transcription-unit hypothesis, not a mapped TSS. For a "hypothetical", co-transcription with a characterised operon is a concrete functional lead (complements the STRING neighborhood channel below).

Published operon evidence (two independent sources)

Two independent published operon maps, cited alongside the distance heuristic above: an association corroborating or contradicting the heuristic, never proof of shared function. REMap's RNA-seq coverage continuity is the most direct of the three signals; Roback's logistic regression and the intergenic-distance heuristic are statistical proxies.

PE/PPE family context (subfamily & T7SS secretion) PE/PPE (unnamed)

Subfamily: PE / PE_PGRS from the Mycobrowser gene name/product; PPE refined to PPE-MPTR / PPE-SVP / PPE-PPW when a dedicated Pfam domain is present (plain PPE otherwise) -- Ates 2020 defines this four-subfamily framework, and the PPE-MPTR mapping (Pfam "Pentapeptide_2") is corroborated gene-by-gene against the literature (PPE10, PPE13), not an invented rule. T7SS locus and secretion status derived from this atlas's own gene nomenclature (the eccA/B/C/D/E and mycP genes already named on the corresponding fiches), not a hard-coded coordinate table. Orphan PE/PPE genes are trans-secreted by ESX-5 (Abdallah et al. 2009). Part of P42 (2026-08-28/29).

Node colour = verdict, dashed = still uncharacterised; edge colour = evidence (green experimental, orange genomic-context, grey co-expression), width ∝ score. Click a partner to open its page; "Explore full network" to walk the graph.

Closest characterised functional partner: sap (integral membrane protein), high confidence (score 707, all STRING channels except text-mining; the partner is chosen on its genomic-context evidence).

All 7 partner(s) at medium confidence are shown. None rests on an interaction measured in M. tuberculosis itself.

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.

Where the experimental evidence comes from, and why it matters here. STRING's experimental channel fuses interactions measured in M. tuberculosis with interactions measured in another organism and transferred to this pair by orthology. The two are not equivalent for this atlas, whose standing rule is that better studied elsewhere is not a function established in M. tuberculosis. Measured on the served network: of the 38 229 partner pairs shown across the atlas, 13 483 partner rows carry a non-zero experimental channel, and only 106 pairs rest on an interaction measured in M. tuberculosis itself — 0.3 % of the network. Those 106 are long-established complexes (ESX-1/ESAT-6, RNA polymerase with CarD and RbpA, the Pup–Mpa proteasome, gyrase, Emb, GarA with PknB and PknG, the Rel modules); no still-uncharacterised gene is among them. The reason is not a gap in this atlas but in the literature: there is almost no experimental interactome of this bacterium, IntAct holding 134 curated protein pairs for a ~4 000-gene proteome. A exp (transferred) badge is therefore a lead, never a measurement, and an absence of badge is not evidence that the pair does not interact.

Evidence

• Legacy H37Rv annotation: hypothetical protein
• MTBC0 PGAP product: sulfolipid-1 biosynthesis membrane-anchored acyltransferase Chp1
• Pfam (hmmscan --cut_ga): PE-PPE PF08237.18 (E=3e-76)
• (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Ancestral MTBC0 protein sequence

>mtbc0_004051|Rv3822|chp1
MKCPGVSDCVATVRHDNVFAIAAGLRWSAAVPPLHKGDAVTKLLVGAIAGGMLACAAILGDGIASADTALIVPGTAPSPYGPLRSLYHFNPAMQPQIGANYYNPTATRHVVSYPGSFWPVTGLNSPTVGSSVSAGTNNLDAAIRSTDGPIFVAGLSQGTLVLDREQARLANDPTAPPPGQLTFIKAGDPNNLLWRAFRPGTHVPIIDYTVPAPVESQYDTINIVGQYDIFSDPPNRPGNLLADLNAIAAGGYYGHSATAFSDPARVAPRDITTTTNSLGATTTTYFIRTDQLPLVRALVDMAGLPPQAAGTVDAALRPIIDRAYQPGPAPAVNPRDLVQGIRGIPAIAPAIAIPIGSTTGASAATSTAAATAAATNALRGANVGPGANKALSMVRGLLPKGKKH