Rv2000 Family assigned · medium auto-curated

H37Rv Rv2000 · MTBC0 mtbc0_002127 · 537 aa · 2268822–2270435 (+) · RefSeq NP_216516.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationFAD/NAD(P)-binding protein
Revised (this work)FAD/NAD(P)-binding protein. Pfam: NAD_binding_8 (PF13450.13).

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

Curated reference (UniProt)

UniProt P9WLN7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2000

UniProt still lists this protein as Uncharacterized protein Rv2000; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
eggNOG descriptionflavoprotein involved in K transport
Orthologous groupCOG0121
Gene Ontology (13) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, GO:0044424, GO:0044444, GO:0044464 +1 more

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 0.255 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 6 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (156) · 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
NAD_binding_8PF13450.13 7.1e-0579–117 NAD(P)-binding Rossmann-like domain

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

Closest characterised functional partner: fabG3 (3-alpha(or 20-beta)-hydroxysteroid dehydrogenase), medium confidence from genomic context alone (score 650 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2001 hyp hypothetical protein 972 973 ctx neighborhood:867 coexpression:804
Rv2002 fabG3 3-alpha(or 20-beta)-hydroxysteroid dehydrogenase 650 650 ctx neighborhood:605
Rv1999c transporter 556 555 ctx neighborhood:554
Rv3633 hyp hypothetical protein 532 513 ctx cooccurence:509
Rv1730c penicillin-binding protein 466 466 ctx cooccurence:462
Rv1311 atpC ATP synthase subunit epsilon 462 462
Rv1308 atpA ATP synthase subunit alpha 435 436 experimental:427
Rv1998c hyp hypothetical protein 452 430
Rv1507c hyp hypothetical protein 412 413
Rv1309 atpG ATP synthase subunit gamma 412 413
Rv3456c rplQ 50S ribosomal protein L17 407 407
Rv1310 atpD ATP synthase subunit beta 403 404
Rv3846 sodA superoxide dismutase 412 403
Rv3461c rpmJ 50S ribosomal protein L36 400 401
Rv0363c fba fructose-bisphosphate aldolase 410 388

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: FAD/NAD(P)-binding protein
  • Pfam (hmmscan --cut_ga): NAD_binding_8 PF13450.13 (E=7e-05)
  • (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_216516.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_8 (PF13450.13)
  • 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 COG0121
  • Curated reference: UniProt P9WLN7 (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 — 21 functional partner(s); context anchor fabG3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002127|Rv2000|
MRPGFVGLGFGQWPVYVVRWPKLHLTPRQRKRVLHRRRLLTDRPISLSQIPIRTGGPMNDPWPRPTQGPAKTIETDYLVIGAGAMGMAFTDTLITESGARVVMIDRACQPGGHWTTAYPFVRLHQPSAYYGVNSRALGNNTIDLVGWNQGLNELAPVGEICAYFDAVLQQQLLPTGRVDYFPMSEYLGDGRFRTLAGTEYVVTVNRRIVDATYLRAVVPSMRPAPYSVAPGVDCVAPNELPKLGTRDRYVVVGAGKTGMDVCLWLLRNDVCPDKLTWIMPRDSWLIDRATLQPGPTFVRQFRESYGATLEAIGAATSTDDLFDRLETAGTLLRIDPSVRPSMYRCATVSHLELEQLRRIRDIVRMGHVQRIEPTTIVLDGGSVPATPTALYIDCTADGAPQRPAKPVFDADHLTLQAVRGCQQVFSAAFIAHVEFAYEDDAVKNELCTPIPHPDCDLDWMRLMHSDLGNFQRWLNDPDLTDWLSSARLNLLADLLPPLSHKPRVRERVVSMFQKRLGTAGDQLAKLLDAATATTEQR