Rv1949c Still unknown · low auto-curated · to review

Annotation: from legacy to revised

Curation note: Added P16.5d: Mycobrowser-annotated gene absent from RefSeq NC_000962.3 (the atlas' original 3906-CDS reference). Foundation record from the Mycobrowser release + translated H37Rv sequence; heavy enrichment layers (structure, orthology, conservation, interaction) pending.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

In the literature (TB corpus sweep)

This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: .

Binding-pocket screen (P2Rank, geometric prediction) no confident pocket

Read with care. This protein (319 aa) is above the size where the detector reliably differentiates proven enzymes (60.5% confident-pocket rate) from proteins annotated as non-catalytic (18.9%; P16.3b calibration). 1 candidate pocket(s) were found but none reached confidence (best probability 0.018), which is consistent with a non-catalytic role, though it does not rule out a shallow or non-canonical binding site that this geometric detector misses. (Individual read at this confidence level; the GROUP-level dark-vs-non-catalytic contrast is NOT statistically significant at this size, p=0.285 -- read as modest evidence, not proof, cf. P16.3c.) P16.3e, calibration phase72b_pocket_calibration.py, 2026-08-03.

Legacy record & comparison (Mycobrowser)

The legacy Mycobrowser record is shown for verification. Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.

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, 145 209 strains)

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.

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.

Proteomics (mass spectrometry) not detected

Not detected in the mass-spectrometry datasets integrated by PaxDb. This is not evidence of absence: low-abundance, condition-specific, or MS-refractory proteins (e.g. small, highly hydrophobic, or repetitive PE/PPE families with few tryptic peptides) are systematically under-sampled.

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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Node colour = verdict, dashed = hypothetical; 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: vapC14 (ribonuclease VapC14), medium confidence from genomic context alone (score 473 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

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 exp badge marks an experimentally-supported partner (measured interaction, experimental/database channel ≥400) as opposed to a purely predicted one — but note that the M. tuberculosis experimental interactome is dominated by a noisy bacterial-two-hybrid screen, so a strong measured link that contradicts the operon/localisation context is likely a false positive. 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.

Ancestral MTBC0 protein sequence

>|Rv1949c|Rv1949c
WLRQRTGADLQIVSGIAEHLRQASGLAREGAGTIGAAQRRVIYAVQDAHNAGFNVEEDLSVTDTRTSRTFAEQAARQAQAQALAGDIRQRATQLIGVEHEVAAKIATATAPLNTVGFHEPPIAPSLPTPVPHNEKPQIHAVDRSWKQDPPSPMPGDPKDMTAVQARAAWDAVNADIARYNARCGRTFVLPNEQAAYDACIADKGSLFERQAAIRARLGELGVPVEGEPPPAPDPAGPQPNEGLPPPGVSPPAESNLTVGPPSRPIQQARGGESLWDENGGEWRYFPGDNYRYPHWDYNPHDSPTARWQNIPIGDLPTHK