Rv1873 Family assigned · medium
H37Rv Rv1873 · MTBC0 mtbc0_001986 ·
145 aa · 2141213–2141650 (+) ·
RefSeq NP_216389.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF1810 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein with an X-ray crystal structure at 1.38 A: a 16.2 kDa monomer adopting a primarily alpha-helical fold with limited similarity to known structures (COG5579). Not a novel fold but a model for sequence-related orthologues. Function unknown. (The UniProt auto-name 'Calpastatin' is a database artefact and is not adopted.) |
Curated reference (UniProt)
| UniProt |
O07756
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Calpastatin |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF1810) |
| Orthologous group | COG5579 |
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 | 0.436 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.84% of strains (1217) · 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 |
|---|---|---|---|---|
DUF1810 | PF08837.17 | 1.6e-57 | 7–142 | Protein of unknown function (DUF1810) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 89.4 (confident). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
2jek-assembly1_A |
1.00 | 0.99 | 1.7e-19 sig | 2jek-assembly1_A Crystal structure of the conserved hypothetical protein Rv1873 from Mycobacterium tuberculosis at 1.38 A |
2nc9-assembly1_A |
0.06 | 0.32 | 6.0e+00 | 2nc9-assembly1_A Apo solution structure of Hop TPR2A |
4gcn-assembly2_B |
0.05 | 0.28 | 4.2e+00 | 4gcn-assembly2_B N-terminal domain of stress-induced protein-1 (STI-1) from C.elegans |
6oiu-assembly3_C |
0.04 | 0.23 | 3.6e+00 | 6oiu-assembly3_C X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350) |
5l0y-assembly3_C |
0.03 | 0.25 | 7.6e+00 | 5l0y-assembly3_C Crystal Structure of a Sec72-ssa1 c-terminal peptide fusion protein |
7ep2-assembly1_B |
0.03 | 0.30 | 8.9e+00 | 7ep2-assembly1_B Crystal structure of ZYG11B bound to GGFN degron |
6oiu-assembly4_D |
0.03 | 0.23 | 6.0e+00 | 6oiu-assembly4_D X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350) |
4iwb-assembly1_A |
0.03 | 0.16 | 2.8e+00 | 4iwb-assembly1_A Novel Fold of FliC/FliS Fusion Protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lldD2 (L-lactate dehydrogenase), high confidence from genomic context alone (score 790 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1872c lldD2 |
L-lactate dehydrogenase | 790 | 790 ctx | neighborhood:790 |
Rv1874 hyp |
hypothetical protein | 596 | 596 ctx | neighborhood:593 |
Rv1875 hyp |
hypothetical protein | 582 | 583 ctx | neighborhood:580 |
Rv1871c hyp |
hypothetical protein | 556 | 556 ctx | neighborhood:556 |
Rv1870c hyp |
hypothetical protein | 443 | 443 ctx | neighborhood:441 |
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
- X-ray crystal structure 1.38 A; alpha-helical fold; COG5579 (Garen 2006, PMID 17142896)
- Limited structural similarity to a repeated motif of other proteins
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216389.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF1810 (PF08837.17)
- 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
COG5579 - Curated reference: UniProt O07756 (TrEMBL, unreviewed; 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)
- Model confidence: ESMFold per-residue pLDDT (mean 89.4, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
5 functional partner(s); context anchor
lldD2 - Primary literature: Garen CR, Cherney MM, Bergmann EM, James MN (2006). The molecular structure of Rv1873, a conserved hypothetical protein from Mycobacterium tuberculosis, at 1.38 A resolution Acta Crystallogr F 62(Pt 12):1201-5. doi:10.1107/S1744309106046902 PMID:17142896
Ancestral MTBC0 protein sequence
>mtbc0_001986|Rv1873| MKSASDPFDLKRFVYAQAPVYRSVVEELRAGRKRGHWMWFVFPQLRGLGSSPLAVRYGISSLEEAQAYLQHDLLGPRLHECTGLVNQVQGRSIEEIFGPPDDLKLCSSMTLFARATDANQDFVALLAKYYGGGEDRRTVALLAVT