Rv2135c Family assigned · medium auto-curated

H37Rv Rv2135c · MTBC0 mtbc0_002268 · 236 aa · 2422564–2423274 (-) · RefSeq NP_216651.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhistidine phosphatase family protein
Revised (this work)Histidine phosphatase family protein. Pfam: His_Phos_1 (PF00300.28).

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

Curated reference (UniProt)

UniProt O06240 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionPhosphoglycerate mutase
Orthologous groupCOG0406
EC number EC 5.4.2.11
KEGG orthology K01834
KEGG pathways map00010, map00260, map00680, map01100, map01110, map01120, map01130, map01200, map01230, map04922, map05230
KEGG modules M00001, M00002, M00003

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 0.722 · 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
His_Phos_1PF00300.28 1.6e-433–198 Histidine phosphatase superfamily (branch 1)

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

Closest characterised functional partner: uppP (undecaprenyl-diphosphatase), high confidence from genomic context alone (score 912 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2133c hyp hypothetical protein 950 951 ctx neighborhood:798 cooccurence:760
Rv2134c hyp hypothetical protein 933 934 ctx neighborhood:800 cooccurence:677
Rv2136c uppP undecaprenyl-diphosphatase 958 912 ctx neighborhood:882 textmining:549
Rv2137c hyp hypothetical protein 800 801 ctx neighborhood:800
Rv2130c mshC cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase 675 676 ctx neighborhood:544
Rv2419c gpgP glucosyl-3-phosphoglycerate phosphatase 944 592 ctx cooccurence:591 textmining:870
Rv2131c cysQ 3'(2'),5'-bisphosphate nucleotidase CysQ 573 549 ctx neighborhood:544
Rv0254c cobU bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase 571 546 ctx cooccurence:419
Rv1695 ppnK inorganic polyphosphate/ATP-NAD kinase 546 546 database:500
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 543 523 coexpression:462
Rv2138 lppL lipoprotein LppL 520 520 ctx neighborhood:513
Rv3199c nudC NADH pyrophosphatase 511 512 database:500
Rv2208 cobS adenosylcobinamide-GDP ribazoletransferase 536 508
Rv0255c cobQ1 cobyric acid synthase 523 501 coexpression:415
Rv3214 gpm2 phosphoglycerate mutase 926 457 ctx cooccurence:452 textmining:870

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: histidine phosphatase family protein
  • Pfam (hmmscan --cut_ga): His_Phos_1 PF00300.28 (E=2e-43)
  • (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_216651.1)
  • Domains: Pfam-A via hmmscan --cut_ga — His_Phos_1 (PF00300.28)
  • 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 COG0406
  • Curated reference: UniProt O06240 (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 — 30 functional partner(s); context anchor uppP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002268|Rv2135c|
MTVILLRHARSTSNTAGVLAGRSGVDLDEKGREQATGLIDRIGDLPIRAVASSPMLRCQRTVEPLAEALCLEPLIDDRFSEVDYGEWTGRKIGDLVDEPLWRVVQAHPSAAVFPGGEGLAQVQTRAVAAVREHDRRLADQHGHDVLWLACTHGDVIKAVIADAFGMHLDSFQRITADPGSVSVVRYTQLRPFVLHVNHTGARLAPALQAAASAQGASPEPNAAVPPGDAVIGGSTD