cinA Resolved · high auto-curated

H37Rv Rv1901 · MTBC0 mtbc0_002016 · 430 aa · 2165772–2167064 (+) · RefSeq NP_216417.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)competence damage-inducible protein CinA
MTBC0 PGAP re-annotationcompetence/damage-inducible protein A
Revised (this work)Competence/damage-inducible protein A. Pfam: MoCF_biosynth (PF00994.30), CinA (PF02464.24).

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

Curated reference (UniProt)

UniProt P9WPE3 SwissProt · reviewed · Evidence at protein level
UniProt nameCinA-like protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namecinA
eggNOG descriptionBelongs to the CinA family
Orthologous groupCOG1058
EC number EC 3.5.1.42
KEGG orthology K03742, K03743
KEGG pathways map00760
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 0.647 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (194) · 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
MoCF_biosynthPF00994.30 4.0e-358–178 Probable molybdopterin binding domain
CinAPF02464.24 6.9e-54275–423 Competence-damaged protein

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

Closest characterised functional partner: fmu (16S rRNA m5C967 methyltransferase), high confidence from genomic context alone (score 717 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 978 935 database:900 textmining:687
Rv1330c pncB1 nicotinic acid phosphoribosyltransferase PncB1 977 919 database:900 textmining:729
Rv0573c pncB2 nicotinic acid phosphoribosyltransferase PncB2 960 919 database:900 textmining:532
Rv0212c nadR transcriptional regulator NadR 948 913 database:900 textmining:436
Rv1596 nadC nicotinate-nucleotide pyrophosphatase 971 912 database:900 textmining:694
Rv3199c nudC NADH pyrophosphatase 955 906 database:900 textmining:547
Rv2746c pgsA3 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 880 843 coexpression:733
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 823 769 coexpression:736
Rv1822 pgsA2 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 823 769 coexpression:736
Rv1407 fmu 16S rRNA m5C967 methyltransferase 717 717 ctx neighborhood:544 coexpression:405
Rv1900c lipJ lignin peroxidase LipJ 692 693 ctx neighborhood:686
Rv2737c recA recombinase A 811 595 textmining:554
Rv1899c lppD lipoprotein LppD 592 593 ctx neighborhood:580
Rv0014c pknB serine/threonine-protein kinase PknB 592 578 ctx neighborhood:544
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 566 566 ctx neighborhood:544

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: competence damage-inducible protein CinA
  • MTBC0 PGAP product: competence/damage-inducible protein A
  • Pfam (hmmscan --cut_ga): MoCF_biosynth PF00994.30 (E=4e-35), CinA PF02464.24 (E=7e-54)
  • (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_216417.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MoCF_biosynth (PF00994.30), CinA (PF02464.24)
  • 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 COG1058
  • Curated reference: UniProt P9WPE3 (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 — 103 functional partner(s); context anchor fmu
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002016|Rv1901|cinA
MAVSARAGIVITGTEVLTGRVQDRNGPWIADRLLELGVELAHITICGDRPADIEAQLRFMAEQGVDLIVTSGGLGPTADDMTVEVVARYCGRELVLDDELENRIANILKKLMGRNPAIEPANFDSIRAANRKQAMIPAGSQVIDPVGTAPGLVVPGRPAVMVLPGPPRELQPIWSKAIQTAPVQDAIAGRTTYRQETIRIFGLPESSLADTLRDAEAAIPGFDLVEITTCLRRGEIEMVTRFEPNAAQVYTQLARLLRDRHGHQVYSEDGASVDELVAKLLTGRRIATAESCTAGLLAARLTDRPGSSKYVAGAVVAYSNEAKAQLLGVDPALIEAHGAVSEPVAQAMAAGALQGFGADTATAITGIAGPSGGTPEKPVGTVCFTVLLDDGRTTTRTVRLPGNRSDIRERSTTVAMHLLRRTLSGIPGSP