ffh Resolved · high auto-curated

H37Rv Rv2916c · MTBC0 mtbc0_003098 · 525 aa · 3245537–3247114 (-) · RefSeq NP_217432.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)signal recognition particle protein
MTBC0 PGAP re-annotationsignal recognition particle protein
Revised (this work)Signal recognition particle protein. Pfam: SRP54_N (PF02881.25), SRP54 (PF00448.29), SRP_SPB (PF02978.27).

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

Curated reference (UniProt)

UniProt P9WGD7 SwissProt · reviewed · Evidence at protein level
UniProt nameSignal recognition particle protein
EC (curated) EC 3.6.5.4
Curated functionInvolved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane. Binds to the hydrophobic signal sequence of the ribosome-nascent chain (RNC) as it emerges from the ribosomes. The SRP-RNC complex is then targeted to the cytoplasmic membrane where it interacts with the SRP receptor FtsY (By similarity). Most of the substrate proteins are involved in stress regulation, lipid metabolism, intermediary metabolism, and cell wall processes. Shows GTPase activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category U Intracellular trafficking, secretion and vesicular transport
Preferred nameffh
eggNOG descriptionInvolved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane. Binds to the hydrophobic signal sequence of the ribosome-nascent chain (RNC) as it emerges from the ribosomes. The SRP-RNC complex is then targeted to the cytoplasmic membrane where it interacts with the SRP receptor FtsY
Orthologous groupCOG0541
EC number EC 3.6.5.4
KEGG orthology K03106
KEGG pathways map02024, map03060, map03070
KEGG modules M00335
Gene Ontology (10) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, 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 0.528 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
SRP54_NPF02881.25 1.8e-215–82 SRP54-type protein, helical bundle domain
SRP54PF00448.29 1.8e-68100–302 SRP54-type protein, GTPase domain
SRP_SPBPF02978.27 1.2e-42316–439 Signal peptide binding domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv2921c ftsY signal recognition particle receptor FtsY 998 995 experimental:829 database:935 textmining:811
Rv0732 secY preprotein translocase SecY 985 964 experimental:471 database:933 textmining:625
Rv0638 secE1 preprotein translocase SecE 981 954 experimental:446 database:900 textmining:622
Rv1440 secG protein-export membrane protein SecG 959 943 experimental:446 database:900
Rv0702 rplD 50S ribosomal protein L4 943 920 experimental:827
Rv3921c yidC membrane protein insertase YidC 956 917 database:900 textmining:496
Rv0703 rplW 50S ribosomal protein L23 922 913 experimental:829
Rv0718 rpsH 30S ribosomal protein S8 920 909 experimental:793
Rv2890c rpsB 30S ribosomal protein S2 917 908 experimental:802
Rv2588c yajC membrane protein secretion factor YajC 983 904 database:900 textmining:838
Rv3240c secA1 protein translocase subunit SecA 986 903 database:900 textmining:862
Rv1821 secA2 accessory Sec system translocase SecA2 973 902 database:900 textmining:740
Rv0721 rpsE 30S ribosomal protein S5 924 901 coexpression:403 experimental:801
Rv0715 rplX 50S ribosomal protein L24 905 900 experimental:828
Rv0651 rplJ 50S ribosomal protein L10 904 900 experimental:826

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: signal recognition particle protein
  • MTBC0 PGAP product: signal recognition particle protein
  • Pfam (hmmscan --cut_ga): SRP54_N PF02881.25 (E=2e-21), SRP54 PF00448.29 (E=2e-68), SRP_SPB PF02978.27 (E=1e-42)
  • (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_217432.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SRP54_N (PF02881.25), SRP54 (PF00448.29), SRP_SPB (PF02978.27)
  • 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 COG0541
  • Curated reference: UniProt P9WGD7 (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 — 155 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003098|Rv2916c|ffh
MFESLSDRLTAALQGLRGKGRLTDADIDATTREIRLALLEADVSLPVVRAFIHRIKERARGAEVSSALNPAQQVVKIVNEELISILGGETRELAFAKTPPTVVMLAGLQGSGKTTLAGKLAARLRGQGHTPLLVACDLQRPAAVNQLQVVGERAGVPVFAPHPGASPESGPGDPVAVAAAGLAEARAKHFDVVIVDTAGRLGIDEELMAQAAAIRDAINPDEVLFVLDAMIGQDAVTTAAAFGEGVGFTGVALTKLDGDARGGAALSVREVTGVPILFASTGEKLEDFDVFHPDRMASRILGMGDVLSLIEQAEQVFDAQQAEEAAAKIGAGELTLEDFLEQMLAVRKMGPIGNLLGMLPGAAQMKDALAEVDDKQLDRVQAIIRGMTPQERADPKIINASRRLRIANGSGVTVSEVNQLVERFFEARKMMSSMLGGMGIPGIGRKSATRKSKGAKGKSGKKSKKGTRGPTPPKVKSPFGVPGMPGLAGLPGGLPDLSQMPKGLDELPPGLADFDLSKLKFPGKK