Rv0448c Still unknown · low auto-curated
H37Rv Rv0448c · MTBC0 - ·
221 aa · 536504–537169 (-) ·
RefSeq NP_214962.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF1365. Function unknown. Foldseek best (non-significant) hit: 5n48-assembly2_C Structure of Anticalin N9B in complex with extra-doma (prob 0.04, TM 0.38). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O53733
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | DUF1365 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF1365) |
| Orthologous group | COG3496 |
| KEGG orthology |
K09701
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 2 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 |
|---|---|---|---|---|
DUF1365 | PF07103.17 | 2.8e-60 | 2–221 | Protein of unknown function (DUF1365) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 92.0 (very high). 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 |
|---|---|---|---|---|
5n48-assembly2_C |
0.04 | 0.38 | 7.1e+00 | 5n48-assembly2_C Structure of Anticalin N9B in complex with extra-domain B of human oncofetal fibronectin |
8gnh-assembly1_B |
0.03 | 0.31 | 3.8e+00 | 8gnh-assembly1_B Complex structure of BD-218 and Spike protein |
6tav-assembly1_C |
0.03 | 0.18 | 5.4e-01 | 6tav-assembly1_C Crystal structure of endopeptidase-induced alpha2-macroglobulin |
8ovj-assembly1_Sd |
0.02 | 0.29 | 5.7e+00 | 8ovj-assembly1_Sd CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME : PARENTAL STRAIN |
7nwt-assembly1_CC |
0.02 | 0.24 | 4.3e+00 | 7nwt-assembly1_CC Initiated 70S ribosome in complex with 2A protein from encephalomyocarditis virus (EMCV) |
7bny-assembly2_B |
0.02 | 0.23 | 3.6e+00 | 7bny-assembly2_B Structure of 2A protein from encephalomyocarditis virus (EMCV) |
6gf6-assembly1_B |
0.02 | 0.18 | 1.5e+00 | 6gf6-assembly1_B Molecular basis of egg coat filament cross-linking: high-resolution structure of the partially deglycosylated ZP1 ZP-N1 domain homodimer |
3w58-assembly2_D |
0.01 | 0.24 | 6.3e+00 | 3w58-assembly2_D Crystal structure of Galectin-1 in the lactose-unbound state(P21) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ufaA1 (cyclopropane-fatty-acyl-phospholipid synthase UfaA), high confidence from genomic context alone (score 993 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) |
|---|---|---|---|---|
Rv0447c ufaA1 |
cyclopropane-fatty-acyl-phospholipid synthase UfaA | 993 | 993 ctx | neighborhood:882 fusion:714 cooccurence:750 |
Rv0449c hyp |
hypothetical protein | 984 | 982 ctx | neighborhood:803 fusion:568 cooccurence:774 |
Rv0446c |
transmembrane protein | 971 | 972 ctx | neighborhood:882 cooccurence:767 |
Rv0445c sigK |
ECF RNA polymerase sigma factor SigK | 828 | 827 ctx | neighborhood:726 |
Rv0444c rskA |
anti-sigma-K factor RskA | 674 | 673 ctx | neighborhood:611 |
Rv2875 mpt70 |
major secreted immunogenic protein Mpt70 | 567 | 567 | coexpression:514 |
Rv0450c mmpL4 |
transmembrane transport protein MmpL4 | 538 | 538 ctx | neighborhood:538 |
Rv0451c mmpS4 |
membrane protein MmpS4 | 509 | 509 ctx | neighborhood:509 |
Rv3392c cmaA1 |
cyclopropane mycolic acid synthase CmaA | 491 | 471 | |
Rv3720 |
fatty acid synthase | 472 | 451 | |
Rv0643c mmaA3 |
methoxy mycolic acid synthase MmaA3 | 442 | 419 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF1365 PF07103.17 (E=3e-60)
- Foldseek best: 5n48-assembly2_C Structure of Anticalin N9B in complex with extra-domain B of hu (prob 0.04, E=7e+00, TM=0.38)
- (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_214962.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF1365 (PF07103.17)
- 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
COG3496 - Curated reference: UniProt O53733 (TrEMBL, unreviewed; Predicted)
- 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 92.0, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
11 functional partner(s); context anchor
ufaA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0448c| MHHSFAYRSYSWYVDVDNLPQLPWWLRPFARFHADDHFADPFSCPPHSSLRDRLDAFFAARGLAVPDGRITALLQARVLGYVFNPLSIFWCHDRDGQLRHVIAEVHNTYGGRHAYLLPPADLPVVTAKNFYVSPFHQLAGYYLIRAPRPDRELDVTVTLHRDRRQVCPEFTATLRGQRRPATTRQIAMMQIISPLAPMVVAARIRIQGIRLWLRRVPVVPR