Rv1312 Still unknown · low

H37Rv Rv1312 · MTBC0 mtbc0_001404 · 147 aa · 1476727–1477170 (+) · RefSeq NP_215828.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2550 domain-containing protein
Revised (this work)DUF2550; Foldseek best hit (PH domain, TM 0.46) not conclusive. Function unknown.

Curated reference (UniProt)

UniProt P9WM29 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1312

UniProt still lists this protein as Uncharacterized protein Rv1312; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2550)
Orthologous group2E6YX

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) pseudogene candidate

pN/pS 0.173 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 10.67% of strains (15493) · 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)

PfamAccessioni-EvalueResiduesDescription
DUF2550PF10739.16 3.6e-4011–139 Protein of unknown function (DUF2550)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 93.0 (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.

TargetProbTME-valueDescription
5l81-assembly1_A 1.00 0.46 1.2e-03 sig 5l81-assembly1_A Crystal structure of the PH domain of murine kindlin-3
3voq-assembly1_B 1.00 0.57 5.8e-03 sig 3voq-assembly1_B Crystal structure of the pleckstrin homology domain of human Sin1, a TORC2 subunit
7lc1-assembly2_D 1.00 0.53 3.2e-03 sig 7lc1-assembly2_D Crystal Structure of KRAS4b (GMPPNP-bound) in complex with the RBD-PH domains of SIN1
5l81-assembly2_B 1.00 0.59 1.3e-02 5l81-assembly2_B Crystal structure of the PH domain of murine kindlin-3
3voq-assembly1_A 1.00 0.54 9.6e-03 sig 3voq-assembly1_A Crystal structure of the pleckstrin homology domain of human Sin1, a TORC2 subunit
6nf1-assembly1_A 1.00 0.58 1.5e-02 6nf1-assembly1_A Vav1 inhibited by an allosteric inhibitor: Vav1 inhibitors block GEF activity
3bji-assembly1_A 1.00 0.58 2.2e-02 3bji-assembly1_A Structural Basis of Promiscuous Guanine Nucleotide Exchange by the T-Cell Essential Vav1
6new-assembly1_A 1.00 0.59 2.7e-02 6new-assembly1_A Apo structure of the activated truncation of Vav1

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: atpC (ATP synthase subunit epsilon), high confidence from genomic context alone (score 881 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1311 atpC ATP synthase subunit epsilon 881 881 ctx neighborhood:881
Rv1309 atpG ATP synthase subunit gamma 812 812 ctx neighborhood:812
Rv1308 atpA ATP synthase subunit alpha 812 812 ctx neighborhood:812
Rv1310 atpD ATP synthase subunit beta 812 812 ctx neighborhood:812
Rv1305 atpE ATP synthase subunit C 737 738 ctx neighborhood:738
Rv3268 hyp hypothetical protein 697 697 ctx cooccurence:697
Rv1307 atpH ATP synthase subunit b/delta 632 632 ctx neighborhood:632
Rv3244c lpqB lipoprotein LpqB 632 632 ctx cooccurence:632
Rv2712c hyp hypothetical protein 612 612 ctx cooccurence:612
Rv1306 atpF ATP synthase subunit B 603 603 ctx neighborhood:603
Rv2342 hyp hypothetical protein 545 545 ctx cooccurence:545
Rv3910 murJ peptidoglycan biosynthesis protein 630 534 ctx cooccurence:534
Rv0862c hyp hypothetical protein 497 497 ctx cooccurence:497
Rv1304 atpB ATP synthase subunit A 494 494 ctx neighborhood:494
Rv2518c ldtB L,D-transpeptidase LdtB 493 493 ctx cooccurence:493

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

  • MTBC0 PGAP product: DUF2550 domain-containing protein
  • Pfam: DUF2550 PF10739.16
  • Foldseek best: 5l81-assembly1_A Crystal structure of the PH domain of murine kindlin-3 (prob 1.00, E=1e-03, TM=0.46)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_215828.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2550 (PF10739.16)
  • 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 2E6YX
  • Curated reference: UniProt P9WM29 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 93.0, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 37 functional partner(s); context anchor atpC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001404|Rv1312|
MSAPMIGMVVLVVVLGLAVLALSYRLWKLRQGGTAGIMRDIPAVGGHGWRHGVIRYRGGEAAFYRLSSLRLWPDRRLSRRGVEIISRRAPRGDEFDIMTDEIVVVELCDSTQDRRVGYEIALDRGALTAFLSWLESRPSPRARRRSM