MTBC Gene Atlas

Rv2681 Resolved · high auto-curated

H37Rv Rv2681 · MTBC0 mtbc0_002855 · 438 aa · 3019154–3020470 (+) · RefSeq NP_217197.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationribonuclease D
Revised (this work)Ribonuclease D. Pfam: DNA_pol_A_exo1 (PF01612.27), HRDC (PF00570.29), DNA_pol_A_exoN (PF18305.7).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt I6XF17 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved hypothetical alanine rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namernd
eggNOG description3'-5' exonuclease
Orthologous groupCOG0349
EC number EC 3.1.13.5
KEGG orthology K03684

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 0.213 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 4 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
DNA_pol_A_exo1PF01612.27 1.1e-3545–201 3'-5' exonuclease
HRDCPF00570.29 7.0e-13249–314 HRDC domain
DNA_pol_A_exoNPF18305.7 3.3e-24333–424 3' to 5' exonuclease C-terminal domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv1340 rphA ribonuclease PH 991 988 experimental:921 database:844
Rv1630 rpsA 30S ribosomal protein S1 983 982 coexpression:436 experimental:770 database:805
Rv2680 hyp hypothetical protein 974 975 ctx neighborhood:882 coexpression:744
Rv3458c rpsD 30S ribosomal protein S4 965 965 experimental:827 database:788
Rv3459c rpsK 30S ribosomal protein S11 953 954 experimental:827 database:743
Rv0702 rplD 50S ribosomal protein L4 920 920 experimental:804 database:555
Rv0703 rplW 50S ribosomal protein L23 877 878 experimental:714 database:587
Rv0651 rplJ 50S ribosomal protein L10 854 855 coexpression:413 experimental:449 database:586
Rv0721 rpsE 30S ribosomal protein S5 853 853 database:798
Rv0722 rpmD 50S ribosomal protein L30 852 848 coexpression:417 experimental:431 database:578
Rv0710 rpsQ 30S ribosomal protein S17 843 844 experimental:840
Rv2785c rpsO 30S ribosomal protein S15 838 839 experimental:838
Rv0720 rplR 50S ribosomal protein L18 835 835 experimental:629 database:570
Rv0683 rpsG 30S ribosomal protein S7 829 829 experimental:818
Rv0682 rpsL 30S ribosomal protein S12 825 825 experimental:818

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

  • Legacy H37Rv annotation: hypothetical protein
  • MTBC0 PGAP product: ribonuclease D
  • Pfam (hmmscan --cut_ga): DNA_pol_A_exo1 PF01612.27 (E=1e-35), HRDC PF00570.29 (E=7e-13), DNA_pol_A_exoN PF18305.7 (E=3e-24)
  • (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_217197.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DNA_pol_A_exo1 (PF01612.27), HRDC (PF00570.29), DNA_pol_A_exoN (PF18305.7)
  • 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 COG0349
  • Curated reference: UniProt I6XF17 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 85 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002855|Rv2681|
MCPEPSHAGAAESEGTESEPTPLLRPAGGIPDLCVTVGEIAAAAELLDRGRGPFAVDAERASGFRYSGRAYLIQIRRAEAGTVLIDPVSHGGDPLTVLAPVAEVLSTNEWILHSADQDLPCLAEVGMRPPALYDTELAGRLAGFDRVNLAAMVERLLGLGLTKGHGAADWSKRPLPSAWLNYAALDVELLIELRAAISRVLAEQGKTDWAAQEFEHLRSFESRPPPAAARQDRWRRTSGIHKVHDRRGLAAVRELWTARDRIAQRRDIAPRRILPDSAIIDAAIADPKSVDDLVALPVFGGRNQRRSAAVWWAALAAARESPDPPEIAEPANGPPPPGRWVRRKPAAAARLDAARAALTEVSQRVRVPTENLVSPDLVRRLCWEWEDISQSSPDPIAAVEAYLRTGQARAWQLELVVPILTAALTGAPDAGAQGDDGS