Rv0611c Still unknown · low

H37Rv Rv0611c · MTBC0 mtbc0_000643 · 73 aa · 709513–709734 (-) · RefSeq NP_215125.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF4926 domain-containing protein
Revised (this work)Conserved hypothetical; function unknown. Structure-based hint rejected: weak fold echo (SH3 beta-barrel, eukaryotic); function unknown.

Curated reference (UniProt)

UniProt I6XVR9 TrEMBL · unreviewed · Predicted
UniProt nameDUF4926 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4926)
Orthologous group2EHRH

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 0.741 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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)

PfamAccessioni-EvalueResiduesDescription
DUF4926PF16277.12 1.1e-214–59 Domain of unknown function (DUF4926)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 70.1 (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.

TargetProbTME-valueDescription
1wfw-assembly1_A 1.00 0.60 1.2e-02 1wfw-assembly1_A Solution structure of SH3 domain of mouse Kalirin-9a protein
8bnv-assembly1_A 1.00 0.69 2.1e-02 8bnv-assembly1_A Crystal structure of Pif1 from Deferribacter desulfuricans in apo from
3gpl-assembly2_B 1.00 0.66 7.6e-02 3gpl-assembly2_B Crystal structure of the ternary complex of RecD2 with DNA and ADPNP
3e1s-assembly1_A 0.99 0.67 1.8e-01 3e1s-assembly1_A Structure of an N-terminal truncation of Deinococcus radiodurans RecD2
2kgt-assembly1_A 0.98 0.63 1.1e-01 2kgt-assembly1_A Solution structure of SH3 domain of PTK6
2ke9-assembly1_A 0.98 0.63 1.2e-01 2ke9-assembly1_A NMR solution structure of the CASKIN SH3 domain
8b1t-assembly1_D 0.97 0.53 6.8e-02 8b1t-assembly1_D RecBCD-DNA in complex with the phage protein Abc2
1v1c-assembly1_A 0.89 0.62 3.6e-01 1v1c-assembly1_A Solution Structure of the SH3 domain of Obscurin

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

Closest characterised functional partner: vapC24 (ribonuclease VapC24), medium confidence from genomic context alone (score 522 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0610c hyp hypothetical protein 667 667 ctx neighborhood:662
Rv0612 hyp hypothetical protein 582 582 ctx neighborhood:579
Rv0240 vapC24 ribonuclease VapC24 521 522 ctx cooccurence:516
Rv2549c vapC20 ribonuclease VapC20 517 518 ctx cooccurence:515
Rv1397c vapC10 ribonuclease VapC10 514 514 ctx cooccurence:511
Rv0355c PPE8 PPE family protein PPE8 472 473 ctx cooccurence:470
Rv3081 hyp hypothetical protein 456 456 ctx cooccurence:456
Rv3350c PPE56 PPE family protein PPE56 433 433 ctx cooccurence:433
Rv3347c PPE55 PPE family protein PPE55 431 432 ctx cooccurence:430
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 426 426 ctx cooccurence:426
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 426 426 ctx cooccurence:426
Rv0872c PE_PGRS15 PE-PGRS family protein PE_PGRS15 425 425 ctx cooccurence:425
Rv1917c PPE34 PPE family protein PPE34 416 417 ctx cooccurence:416
Rv2949c chorismate pyruvate-lyase 414 415 ctx cooccurence:411
Rv2209 integral membrane protein 403 404 ctx cooccurence:400

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

  • Structural Foldseek hit not propagated -- weak fold echo (SH3 beta-barrel, eukaryotic); function unknown
  • Reviewed against literature (extended structural cross-check, 2026-06-02)

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_215125.2)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4926 (PF16277.12)
  • 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 2EHRH
  • Curated reference: UniProt I6XVR9 (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 70.1, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 15 functional partner(s); context anchor vapC24
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000643|Rv0611c|
MYAEHDVVVLTRDVPDKSLIAGDVGAVVGRYAAGGYEVDFTAANGCTVAVVTLAGDDIRPRRRREIPHVREVA