Rv1216c Family assigned · medium auto-curated

H37Rv Rv1216c · MTBC0 mtbc0_001304 · 224 aa · 1367914–1368588 (-) · RefSeq NP_215732.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane protein
MTBC0 PGAP re-annotationisoprenylcysteine carboxylmethyltransferase family protein
Revised (this work)Isoprenylcysteine carboxylmethyltransferase family protein. Pfam: DUF1295 (PF06966.18), PEMT (PF04191.19), ICMT (PF04140.20).

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

Curated reference (UniProt)

UniProt O05317 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved integral membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionPFAM Isoprenylcysteine carboxyl methyltransferase
Orthologous groupCOG2020

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 0.249 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (242) · 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
DUF1295PF06966.18 4.0e-05104–213 Protein of unknown function (DUF1295)
PEMTPF04191.19 1.5e-10111–204 Phospholipid methyltransferase
ICMTPF04140.20 9.6e-08133–202 Isoprenylcysteine carboxyl methyltransferase (ICMT) family

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

Closest characterised functional partner: Rv1217c (tetronasin ABC transporter integral membrane protein), high confidence from genomic context alone (score 954 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1217c tetronasin ABC transporter integral membrane protein 964 954 ctx neighborhood:834 coexpression:735
Rv1218c tetronasin ABC transporter ATP-binding protein 901 831 ctx neighborhood:801 textmining:438
Rv1219c raaS transcriptional regulator 916 812 ctx neighborhood:801 textmining:573
Rv1215c hyp hypothetical protein 927 746 ctx neighborhood:744 textmining:724
Rv1220c methyltransferase 653 537 ctx neighborhood:536
Rv0701 rplC 50S ribosomal protein L3 462 462
Rv1214c PE14 PE family protein PE14 447 447 ctx neighborhood:447
Rv3707c hyp hypothetical protein 437 437 ctx cooccurence:436
Rv0709 rpmC 50S ribosomal protein L29 431 432
Rv2120c integral membrane protein 425 426 ctx cooccurence:422
Rv3810 pirG cell surface protein 415 416
Rv1388 mihF integration host factor MihF 413 414 coexpression:413
Rv3460c rpsM 30S ribosomal protein S13 412 413 coexpression:412
Rv0538 membrane protein 426 406 coexpression:404
Rv3489 hyp hypothetical protein 724 42 textmining:724

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: integral membrane protein
  • MTBC0 PGAP product: isoprenylcysteine carboxylmethyltransferase family protein
  • Pfam (hmmscan --cut_ga): DUF1295 PF06966.18 (E=4e-05), PEMT PF04191.19 (E=1e-10), ICMT PF04140.20 (E=1e-07)
  • (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_215732.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF1295 (PF06966.18), PEMT (PF04191.19), ICMT (PF04140.20)
  • 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 COG2020
  • Curated reference: UniProt O05317 (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 — 15 functional partner(s); context anchor Rv1217c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001304|Rv1216c|
MHIGLKIFIWGVLGLVVFGALLFGPAGTFDYWQAWVFLAAFVSTTIGPTIYLARNDPAALQRRMRSGPLAEGRTIQKFIVIGAFLGFFAMMVLSACDHRYGWSSVPAAVCVIGDVLVMTGLGIAMLVVIQNRYAASTVRVEAGQILASDGLYKIVRHPMYAGNVVMMTGIPLALGSYWAMFILVPGTLVLVFRILDEEKLLTQELSGYREYRQLVRYRLVPYVW