dipZ Resolved · high auto-curated

H37Rv Rv2874 · MTBC0 - · 695 aa · 3184847–3186934 (+) · RefSeq NP_217390.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane C-type cytochrome biogenesis protein DipZ
MTBC0 PGAP re-annotation
Revised (this work)Integral membrane C-type cytochrome biogenesis protein DipZ. Pfam: DsbD_TM (PF02683.23), Redoxin (PF08534.17), AhpC-TSA (PF00578.28), Thioredoxin_10 (PF17991.8).

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 P9WG63 SwissProt · reviewed · Evidence at protein level
UniProt nameProtein DipZ

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
O Post-translational modification, protein turnover, chaperones
Preferred namedipZ
eggNOG descriptionbiogenesis protein
Orthologous groupCOG0526
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.649 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (169) · 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
DsbD_TMPF02683.23 1.2e-27116–334 Cytochrome C biogenesis protein transmembrane domain
RedoxinPF08534.17 3.1e-09400–529 Redoxin
AhpC-TSAPF00578.28 1.1e-12413–523 AhpC/TSA family
Thioredoxin_10PF17991.8 2.6e-32568–695 Thioredoxin like C-terminal domain

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

Closest characterised functional partner: mpt70 (major secreted immunogenic protein Mpt70), high confidence from genomic context alone (score 853 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2875 mpt70 major secreted immunogenic protein Mpt70 949 853 ctx neighborhood:775 textmining:668
Rv0137c msrA peptide methionine sulfoxide reductase MsrA 884 839 experimental:562 database:596
Rv2428 ahpC alkyl hydroperoxide reductase subunit AhpC 873 834 experimental:468 database:611
Rv0794c oxidoreductase 766 755 experimental:410 database:550
Rv2713 sthA pyridine nucleotide transhydrogenase 765 754 experimental:410 database:550
Rv0462 lpdC dihydrolipoamide dehydrogenase 804 753 experimental:410 database:550
Rv2855 mtr mycothione reductase 765 753 experimental:410 database:550
Rv3303c lpdA NAD(P)H quinone reductase LpdA 765 753 experimental:410 database:550
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 711 697 database:578
Rv3051c nrdE ribonucleoside-diphosphate reductase subunit alpha 711 697 database:578
Rv2674 msrB peptide methionine sulfoxide reductase MsrB 775 694 database:594
Rv3446c hyp hypothetical protein 707 675 database:444
Rv1937 oxygenase 717 674 database:506
Rv0529 ccsA cytochrome C-type biogenesis protein CcsA 914 666 coexpression:619 textmining:754
Rv2873 mpt83 cell surface lipoprotein 821 660 ctx neighborhood:485 textmining:496

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): integral membrane C-type cytochrome biogenesis protein DipZ
  • Pfam (hmmscan --cut_ga): DsbD_TM PF02683.23 (E=1e-27), Redoxin PF08534.17 (E=3e-09), AhpC-TSA PF00578.28 (E=1e-12), Thioredoxin_10 PF17991.8 (E=3e-32)
  • (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_217390.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DsbD_TM (PF02683.23), Redoxin (PF08534.17), AhpC-TSA (PF00578.28), Thioredoxin_10 (PF17991.8)
  • 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 COG0526
  • Curated reference: UniProt P9WG63 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 122 functional partner(s); context anchor mpt70
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2874|dipZ
MVESRRAAAAASAYASRCGIAPATSQRSLATPPTISVPSGEGRCRCHVARGAGRDPRRRLRRRRWCGRCGYHSHLTGGEFDVNRLCQQRSRERSCQLVAVPADPRPKRQRITDVLTLALVGFLGGLITGISPCILPVLPVIFFSGAQSVDAAQVAKPEGAVAVRRKRALSATLRPYRVIGGLVLSFGMVTLLGSALLSVLHLPQDAIRWAALVALVAIGAGLIFPRFEQLLEKPFSRIPQKQIVTRSNGFGLGLALGVLYVPCAGPILAAIVVAGATATIGLGTVVLTATFALGAALPLLFFALAGQRIAERVGAFRRRQREIRIATGSVTILLAVALVFDLPAALQRAIPDYTASLQQQISTGTEIREQLNLGGIVNAQNAQLSNCSDGAAQLESCGTAPDLKGITGWLNTPGNKPIDLKSLRGKVVLIDFWAYSCINCQRAIPHVVGWYQAYKDSGLAVIGVHTPEYAFEKVPGNVAKGAANLGISYPIALDNNYATWTNYRNRYWPAEYLIDATGTVRHIKFGEGDYNVTETLVRQLLNDAKPGVKLPQPSSTTTPDLTPRAALTPETYFGVGKVVNYGGGGAYDEGSAVFDYPPSLAANSFALRGRWALDYQGATSDGNDAAIKLNYHAKDVYIVVGGTGTLTVVRDGKPATLPISGPPTTHQVVAGYRLASETLEVRPSKGLQVFSFTYG