Rv1272c Family assigned · medium auto-curated

H37Rv Rv1272c · MTBC0 mtbc0_001362 · 631 aa · 1429393–1431288 MTBC0 (-) · RefSeq NP_215788.1

Genomic neighbourhood (genome browser)

This gene (outlined) in its genomic context; arrows are neighbouring genes coloured by verdict. Click any gene to navigate. Pan and zoom in the full browser.

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)	drug ABC transporter ATP-binding protein
MTBC0 PGAP re-annotation	fatty acid ABC transporter ATP-binding protein/permease
Revised (this work)	Fatty acid ABC transporter ATP-binding protein/permease. Pfam: ABC_membrane (PF00664.29), ABC_tran (PF00005.34).
Functional category (TubercuList)	cell wall and cell processes

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

In the literature (TB corpus sweep) 4 publications

4 TB publications mention this gene. 4 publication(s) discuss this gene (4 in a M. tuberculosis context, 1 in other mycobacteria — ).


Publication	Date
A copper uptake ABC transport system is essential for Mycobacterium tuberculosis virulence. doi:10.1080/22221751.2026.2668753	2026
Mycobacterium tuberculosis-derived linoleic acid increases regulatory T cell function to promote bacterial survival within macrophages. doi:10.1038/s41564-025-02140-2	2025
[Investigation of Efflux Pump Genes in Resistant Mycobacterium tuberculosis Complex Clinical Isolates Exposed to First Line Antituberculosis Drugs and Verapamil Combination]. doi:10.5578/mb.20239916	2023
The ABC transporter Rv1272c of Mycobacterium tuberculosis enhances the import of long-chain fatty acids in Escherichia coli. doi:10.1016/j.bbrc.2018.01.115	2018

This layer CITES the literature and adds context; it does not change the verdict or the function stated elsewhere in this fiche. This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: PubMed (whole): H37Rv locus tag + GENE NAME + ortholog identifiers (Mb…, MMAR_…, MSMEG_…, ML…, MAB_…), under a mycobacterial context filter; hits verified against the abstract text. Species-context counts distinguish M. tuberculosis literature from literature on other mycobacteria. phase76/phase77, 2026-07-13.

Genomic-neighbour overlap (structural caveat) co-directional · 0 % of gene

Neighbour	Rv1273c (Rv1273c, - strand)
Overlap	4 bp, 0 % of this gene's length

co-directional overlap: ordinary (e.g. shared stop/start codons in an operon), not the Rv2438A-type artefact P20.1, derived from GFF3 gene coordinates, 2026-08-03.

CRISPRi vulnerability

Vulnerability index 1.11 (95% CI -0.77 to 3.95). A more negative index = more vulnerable to knockdown (better drug-target quality); indicative threshold VI ≤ -6 = highly vulnerable.

Quantitative CRISPRi knockdown, graded (finer than binary Tn-seq essentiality). Source: CRISPRi vulnerability index (Bosch 2021, pebble.rockefeller.edu).

Legacy record & comparison (Mycobrowser)

Mycobrowser function	Thought to be involved in active transport of drugs across the membrane (export): multidrugs resistance by an export mechanism. Responsible for energy coupling to the transport system and for the translocation of the substrate across the membrane.

The legacy Mycobrowser record is shown for verification. Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.

Orthologues (reciprocal best hits across mycobacteria)

M. bovis	`Mb1303c` · 99.8% identity
M. leprae	`ML1113c` · 75.3% identity
M. marinum	`MMAR_4148` · 81.9% identity
M. smegmatis	`MSMEG_5009` · 73.4% identity
M. orygis	`RJtmp_001339` · 99.8% identity
M. abscessus	`MAB_1414c` · 70.9% identity

Reciprocal-best-hit orthologues (DIAMOND) against the Mycobrowser reference proteomes. A missing species is informative: e.g. a gene absent from M. leprae was likely lost in its reductive genome evolution. Locus tags link to Mycobrowser.

Curated reference (UniProt)

UniProt	`P9WQJ3` SwissProt · reviewed · Evidence at protein level
UniProt name	Drug eflux ATP-binding/permease protein Rv1272c
EC (curated)	`EC 7.6.2.-`
Curated function	ABC transporter that contributes to drug efflux (By similarity). Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation (Probable). It is also involved in fatty acid import. When Rv1272c is expressed in E.coli, it enhances the uptake of long-chain fatty acids and their incorporation into phospholipids in the E.coli cell.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category	`V` Defense mechanisms
Preferred name	yfiC
eggNOG description	ABC transporter
Orthologous group	`COG1132`
KEGG orthology	`K06147`

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	1.102 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains)	2 synonymous, 6 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.

Outgroup conservation (beyond the MTBC) Bacteria

M. canettii dN/dS (deep-divergence selection)	0.368 (low power) · 2 consensus substitution(s) low power (2 canettii-consensus substitution(s)); present in M. canettii but dN/dS not reliable
Genus-wide presence (~53 non-MTBC Mycobacterium)	present in 53/53 (100%) · mean identity 80.5% · 4/4 closest MTBAP relatives conserved across the genus (present in 53/53 non-MTBC Mycobacterium genomes, incl. distant relatives) — an ancient core gene predating the genus radiation
Phylostratum (deepest detected homolog)	MTBC-specific → Mycobacterium → Mycobacteriaceae → Corynebacteriales → Actinomycetia → Bacteria detected in 13/13 non-Mycobacterium reference genomes (down to Bacteria) · mean identity 51.7% detected down to outside the phylum (Proteobacteria/Firmicutes controls) — a universally conserved, ancient bacterial gene

Two orthogonal outgroup signals. M. canettii (the immediate outgroup) gives a deep-divergence dN/dS (a low value confirms a constrained, real gene; shown as confident only at ≥8 substitutions, else flagged low-power). Genus-wide presence/absence (tblastn vs assembled non-MTBC genomes) places the gene on the ancient-core ↔ MTBC-specific axis: a gene absent even from the closest MTBAP relatives is a candidate MTBC-specific innovation (possible host-adaptation factor, to confirm by synteny). The phylostratum extends that axis outside the genus (tblastn vs 13 reference genomes spanning Mycobacteriaceae → Corynebacteriales → Actinomycetia → outside the phylum): it is the deepest clade in which a homolog is still detected, i.e. a proxy for gene age. Read it with the null model in mind: a shallow (young) stratum can also reflect homology-detection failure for short or fast-evolving ORFs, so it is a descriptive axis, not a proof of novelty.

Essentiality (transposon mutagenesis)

DeJesus 2017 call	NE · non-essential
What the call means	non-essential
TA sites (Himar1)	31 in the ORF — 0 in the essential state, 0 growth-defect, 31 non-essential, 0 growth-advantage. Saturation 0.806, mean read count 61.16. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction.

Genome-wide Himar1 transposon essentiality in H37Rv (DeJesus 2017). An essential call (ES/ESD/GD) is strong, independent evidence that a "hypothetical" locus encodes a functional, selectively required gene — orthogonal to intra-species conservation.

Mutant phenotypes (conditional Tn-seq, MtbTnDB) in-vivo phenotype

Condition	log2FC	q	Effect
fitness in mouse infection, day 45 (in vivo)	-3.05	0.0	required
fitness in mouse infection (in vivo)	-2.60	0.036	required
fitness in mouse infection (in vivo)	-2.58	0.03	required
fitness in mouse infection (in vivo)	-2.47	0.038	required
fitness after prolonged in vitro passage (in vitro passage)	-2.44	0.022	required
fitness in mouse infection (in vivo)	-2.38	0.035	required
fitness in mouse infection (in vivo)	-2.00	0.012	required
fitness in mouse infection (in vivo)	-1.67	0.029	required
fitness in mouse infection (in vivo)	-1.44	0.043	required
fitness in mouse infection (in vivo)	-1.42	0.042	required

Conditional fitness of transposon-disruption mutants across 10 significant condition(s) (|log2FC|≥1, q≤0.05), from the standardized MtbTnDB compendium. A negative log2FC means the mutant is depleted — the gene contributes to fitness in that condition. An in-vivo defect for a "hypothetical" is strong evidence it matters for infection, even without a known molecular function. Disruption (Tn insertion), not a clean deletion; genetic-interaction screens excluded.

Proteomics (mass spectrometry) detected

MS detection	detected in 9 of 16 independent MS datasets
Integrated abundance	2.15 ppm · rank 3156/3519 (10.3th percentile)

Detection by mass spectrometry is direct, experimental evidence that the protein product exists — orthogonal to sequence conservation and to Tn-seq essentiality, and especially decisive for a "hypothetical" locus. Reproducible detection across several independent datasets (PaxDb) makes the existence claim robust; the integrated abundance places the protein in the proteome's dynamic range.

Predicted localisation (DeepTMHMM + lipobox)

Prediction	predicted membrane protein (6 TM helixes)
DeepTMHMM class	TM
TM helices (DeepTMHMM)	6

Transmembrane topology and signal peptide from DeepTMHMM (deep-learning reference predictor); lipoproteins from a (myco)bacterial lipobox motif. A sequence-based prediction of subcellular context.

Physico-chemical properties (computed, ProtParam)

Length	631 aa
Molecular weight	68.3 kDa
Theoretical pI	9.21
GRAVY	0.152 (hydrophobic)
Aliphatic index	106.7
Aromaticity	0.062
Instability index	34.4 (stable)

Computed from the ancestral MTBC0 sequence with the ExPASy ProtParam method (Biopython). Descriptive biophysical context: a positive GRAVY flags a hydrophobic (often membrane) protein, a high instability index (>40) predicts a short in-vitro half-life, an extreme pI hints at compartment or binding partner.

Domains (Pfam, hmmscan --cut_ga)

Pfam	Accession	i-Evalue	Residues	Description
`ABC_membrane`	PF00664.29	4.1e-60	56–353	ABC transporter transmembrane region
`ABC_tran`	PF00005.34	3.2e-29	414–562	ABC transporter

Experimental structures (Protein Data Bank) 9 solved

PDB	Method	Resolution	Coverage
`9iqg`	Electron Microscopy	2.7 Å	98%
`8xsr`	Electron Microscopy	2.93 Å	98%
`8wcx`	Electron Microscopy	3.09 Å	98%
`8xst`	Electron Microscopy	3.1 Å	98%
`8wcw`	Electron Microscopy	3.11 Å	98%
`8xss`	Electron Microscopy	3.33 Å	98%
`9iqe`	Electron Microscopy	3.78 Å	98%
`9iqf`	Electron Microscopy	4.01 Å	98%

Experimentally solved structures mapped from the UniProt accession via PDBe/SIFTS (9 total; up to 8 shown, ranked by sequence coverage then resolution). An experimental structure is direct proof of the folded product and the strongest structural evidence — superseding the predicted ESMFold/AlphaFold models below for any covered region.

Structural search (AlphaFold DB model, Foldseek vs PDB — genome-wide) pLDDT 88.0

PDB hit	prob	TM-score	E-value	Description
`4q4j-assembly1_B`	1.00	0.85	2.2e-44 sig	4q4j-assembly1_B Structure of crosslinked TM287/288_S498C_S520C mutant
`4q4a-assembly1_B`	1.00	0.85	1.6e-43 sig	4q4a-assembly1_B Improved model of AMP-PNP bound TM287/288
`6quz-assembly1_B`	1.00	0.73	1.4e-43 sig	6quz-assembly1_B Structure of ATPgS-bound outward-facing TM287/288 in complex with sybody Sb_TM35
`4q4j-assembly1_A`	1.00	0.87	2.3e-37 sig	4q4j-assembly1_A Structure of crosslinked TM287/288_S498C_S520C mutant
`6qv1-assembly1_B`	1.00	0.70	9.6e-42 sig	6qv1-assembly1_B Structure of ATPgS-bound outward-facing TM287/288 in complex with nanobody Nb_TM1

Foldseek search of the AlphaFold DB model (mean pLDDT 88.0, gated at 70) against the PDB — a genome-wide extension of the ESMFold dark-gene search that also covers proteins beyond the single-sequence length limit. Confident structural neighbours (E < 0.01) shown.

Genomic context (neighbours & predicted operon) operon of 2

Upstream (5' on genome)	`Rv1271c` (- strand, 107 bp gap)
Downstream (3' on genome)	`Rv1273c` (- strand, -4 bp gap)
Predicted operon	`Rv1272c` · `Rv1273c`

Neighbours from the H37Rv annotation (- strand). The operon is predicted by co-directional intergenic distance (same strand, gaps ≤50 bp) — a transcription-unit hypothesis, not a mapped TSS. For a "hypothetical", co-transcription with a characterised operon is a concrete functional lead (complements the STRING neighborhood channel below).

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

Explore full network →

Node colour = verdict, dashed = hypothetical; edge colour = evidence (green experimental, orange genomic-context, grey co-expression), width ∝ score. Click a partner to open its page; "Explore full network" to walk the graph.

Closest characterised functional partner: Rv1273c (drug ABC transporter ATP-binding protein), high confidence from genomic context alone (score 911 excluding text-mining).

Partner	Product	Score	No text-mining	Channels (≥400)
`Rv1273c`	drug ABC transporter ATP-binding protein	921	911 ctx	neighborhood:881
`Rv1275` lprC	lipoprotein LprC	775	775 ctx	neighborhood:772
`Rv1274` lprB	lipoprotein LprB	775	775 ctx	neighborhood:772
`Rv1218c` exp	tetronasin ABC transporter ATP-binding protein	800	706	database:536
`Rv0435c` exp	ATPase	691	676	database:528
`Rv3884c` eccA2 exp	ESX-2 secretion system protein EccA	686	666	database:528
`Rv0282` eccA3 exp	ESX-3 secretion system protein EccA	683	664	database:528
`Rv3868` eccA1 exp	ESX-1 secretion system protein EccA1	683	663	database:528
`Rv2688c` exp	antibiotic ABC transporter ATP-binding protein	698	661	database:536
`Rv1687c` exp	ABC transporter ATP-binding protein	744	654	database:536
`Rv2115c` mpa exp	proteasome-associated ATPase	648	648	database:539
`Rv1458c` exp	antibiotic ABC transporter ATP-binding protein	653	633	database:536
`Rv1747` exp	ABC transporter ATP-binding protein/permease	669	632	database:536
`Rv2936` drrA exp	daunorubicin ABC transporter ATP-binding protein DrrA	648	632	database:536
`Rv3696c` glpK exp	glycerol kinase	612	592	database:511

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 exp badge marks an experimentally-supported partner (measured interaction, experimental/database channel ≥400) as opposed to a purely predicted one — but note that the M. tuberculosis experimental interactome is dominated by a noisy bacterial-two-hybrid screen, so a strong measured link that contradicts the operon/localisation context is likely a false positive. 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: drug ABC transporter ATP-binding protein
MTBC0 PGAP product: fatty acid ABC transporter ATP-binding protein/permease
Pfam (hmmscan --cut_ga): ABC_membrane PF00664.29 (E=4e-60), ABC_tran PF00005.34 (E=3e-29)
(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_215788.1)
Domains: Pfam-A via hmmscan --cut_ga — ABC_membrane (PF00664.29), ABC_tran (PF00005.34)
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 COG1132
Curated reference: UniProt P9WQJ3 (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)
Genome-wide structure: AlphaFold DB model (Jumper et al. 2021, doi:10.1038/s41586-021-03819-2; Varadi et al. 2024, doi:10.1093/nar/gkad1011) searched vs PDB with Foldseek (mean pLDDT 88.0)
Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 96 functional partner(s); context anchor Rv1273c
Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
Proteomics: integrated mass-spectrometry abundance from PaxDb 5.0 (Huang et al. 2023, doi:10.1016/j.mcpro.2023.100640), taxon 83332 — weighted average of 16 datasets, incl. Schubert et al. 2013 (doi:10.1016/j.chom.2013.04.008) and Albrethsen et al. 2013 (doi:10.1074/mcp.M112.018846)
Functional category: TubercuList scheme (Cole et al. 1998, doi:10.1038/31159), via Mycobrowser (Kapopoulou et al. 2011, doi:10.1016/j.tube.2010.09.006)
Orthologues: reciprocal best hits (DIAMOND, Buchfink et al. 2021, doi:10.1038/s41592-021-01101-x) against Mycobrowser release 5 reference proteomes
Experimental structures: PDBe/SIFTS UniProt→PDB mapping (Dana et al. 2019, doi:10.1093/nar/gky1114)
Genomic context / operon: H37Rv annotation; operon predicted by co-directional intergenic distance (Salgado et al. 2000, doi:10.1073/pnas.030539397)
Mutant phenotypes: standardized Tn-seq compendium MtbTnDB (Jinich et al. 2025, doi:10.1111/mmi.15370), aggregating many primary Tn-seq studies across conditions
Physico-chemical properties: ExPASy ProtParam method via Biopython (Gasteiger et al. 2005), computed from the MTBC0 sequence
Predicted localisation: DeepTMHMM (Hallgren et al. 2022, doi:10.1101/2022.04.08.487609) for transmembrane topology and signal peptide
Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001362|Rv1272c|
MTAPPGARPRAASPPPNMRSRDFWGSAARLVKRLAPQRRLSIAVITLGIAGTTIGVIVPRILGHATDLLFNGVIGRGLPGGITKAQAVASARARGDNTFADLLSGMNVVPGQGVDFAAVERTLALALALYLAAALMIWAQARLLNLTVQKTMVRLRTDVEDKVHRLPLSYFDGQQRGELLSRVTNDIDNLQSSLSMTISQLVTSILTMVAVLAMMVSISGLLALITLLTVPLSLLVTRAITRRSQPLFVAHWTSTGRLNAHLEETYSGFTVVKTFGHQAAARERFHELNDDVYQAGFGAQFLSGLVQPATAFIGNLGYVAVAVAGGLQVATGQITLGSIQAFIQYIRQFNMPLSQLAGMYNALQSGVASAERVFDVLDEPEESPEPEPELPNLTGRVEFEHVNFAYLPGTPVIRDLSLVAEPGSTVAIVGPTGAGKTTLVNLLMRFYEIGSGRILIDGVDIASVSRQSLRSRIGMVLQDTWLYDGTIAENIAYGRPEATTDEIVEAARAAHVDRFVNTLPAGYQTRVSGDGGSISVGEKQLITIARAFLARPQLLILDEATSSVDTRTELLIQRAMRELRRDRTSFIIAHRLSTIRDADHILVVQTGQIVERGNHAELLARRGVYYQMTRA

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