secA

168

preprotein translocase subunit (ATPase), required for membrane targeting of DivIVA, motor protein that drives preprotein translocation through the SecY-SecE-SecG channel

Locus: BSU_35300

Molecular weight: 95.33 kDa

Isoelectric point: 5.34

Protein length: 841 aa

Gene length: 2526 bp

Function: protein secretion

Product: preprotein translocase subunit (ATPase)

Essential: yes

Synonyms: secA, div, div-341, ts-341

Genomic Context

Hide small RNAsZoom:

List of homologs in different organisms, belongs to COG0653 (Galperin et al., 2021)

Gene

Coordinates: 3,628,310  3,630,835

Phenotypes of a mutant

• essential PubMed
• terminal phenotype of CRISPRi knockdown mutant is moderate bending and a cessation of growth PubMed

The protein

Catalyzed reaction/ biological activity

• ATP  ADP + Pi + preprotein translocation
• required for membrane targeting of DivIVA PubMed

Protein family

• SecA family (single member, according to UniProt)

Domains

• nucleotide binding domain, preprotein binding domain, IRA2 domain, scaffold domain, wing domain, IRA1 domain, C-terminal domain

Cofactors

• Mg

Structure

• 1TF5 (PDB) (open structure)
• 2IBM (PDB)
• 3DL8 (PDB) (structure of the (SecY-SecE-SecG)-SecA complex PubMed
• P28366 (AlphaFold)

Effectors of protein activity

• anionic phospholipids, preprotein, SecY, signal peptides (even when added in trans) PubMed

Localization

• mainly in the cytoplasm PubMed
• a small fraction is statically associated with the cell membrane PubMed

Additional information

• subject to Clp-dependent proteolysis upon glucose starvation PubMed

Expression and Regulation

Operons

• Genes: secA-prfB

  Description: PubMed

  Sigma factors

  • SigA: sigma factor, PubMed, in sigA regulon

Biological materials

Mutant

• BEC35300, a CRISPRi knockdown mutant, is available from the Bacillus Genetic Stock Center

References

Reviews

Tsirigotaki A, De Geyter J, Šoštaric N, Economou A, Karamanou S Protein export through the bacterial Sec pathway. Nature reviews. Microbiology. 2017 Jan; 15(1):21-36. doi:10.1038/nrmicro.2016.161. PMID:27890920
Collinson I SecA-a New Twist in the Tale. Journal of bacteriology. 2017 Jan 15; 199(2). pii:e00736-16. doi:10.1128/JB.00736-16. PMID:27799326
Kang Z, Yang S, Du G, Chen J Molecular engineering of secretory machinery components for high-level secretion of proteins in Bacillus species. Journal of industrial microbiology & biotechnology. 2014 Nov; 41(11):1599-607. doi:10.1007/s10295-014-1506-4. PMID:25212246

Original Publications

Fiedler SM, Graumann PLB. subtilis Sec and Srp Systems Show Dynamic Adaptations to Different Conditions of Protein Secretion.Cells. 2024 Feb 22; 13(5). PMID: 38474341
Cui P, Li X, Zhu M, Wang B, Liu J, Chen H Design, synthesis and antibacterial activities of thiouracil derivatives containing acyl thiourea as SecA inhibitors. Bioorganic & medicinal chemistry letters. 2016 Nov 23; . pii:S0960-894X(16)31212-4. doi:10.1016/j.bmcl.2016.11.060. PMID:28041832
Banerjee T, Lindenthal C, Oliver D SecA functions in vivo as a discrete anti-parallel dimer to promote protein transport. Molecular microbiology. 2017 Feb; 103(3):439-451. doi:10.1111/mmi.13567. PMID:27802584
Huber D, Jamshad M, Hanmer R, Schibich D, Döring K, Marcomini I, Kramer G, Bukau B SecA Cotranslationally Interacts with Nascent Substrate Proteins In Vivo. Journal of bacteriology. 2017 Jan 15; 199(2). pii:e00622-16. doi:10.1128/JB.00622-16. PMID:27795329
Dajkovic A, Hinde E, MacKichan C, Carballido-Lopez R Dynamic Organization of SecA and SecY Secretion Complexes in the B. subtilis Membrane. PloS one. 2016; 11(6):e0157899. doi:10.1371/journal.pone.0157899. PMID:27336478
Peters JM, Colavin A, Shi H, Czarny TL, Larson MH, Wong S, Hawkins JS, Lu CH, Koo BM, Marta E, Shiver AL, Whitehead EH, Weissman JS, Brown ED, Qi LS, Huang KC, Gross CA A Comprehensive, CRISPR-based Functional Analysis of Essential Genes in Bacteria. Cell. 2016 Jun 02; 165(6):1493-506. doi:10.1016/j.cell.2016.05.003. pii:S0092-8674(16)30551-7. PMID:27238023
Wowor AJ, Yan Y, Auclair SM, Yu D, Zhang J, May ER, Gross ML, Kendall DA, Cole JL Analysis of SecA dimerization in solution. Biochemistry. 2014 May 20; 53(19):3248-60. doi:10.1021/bi500348p. PMID:24786965
Halbedel S, Kawai M, Breitling R, Hamoen LW SecA is required for membrane targeting of the cell division protein DivIVA in vivo. Frontiers in microbiology. 2014; 5:58. doi:10.3389/fmicb.2014.00058. PMID:24592260
Yang CK, Lu CD, Tai PC Differential expression of secretion machinery during bacterial growth: SecY and SecF decrease while SecA increases during transition from exponential phase to stationary phase. Current microbiology. 2013 Dec; 67(6):682-7. doi:10.1007/s00284-013-0421-7. PMID:23852076
Cui J, Jin J, Hsieh YH, Yang H, Ke B, Damera K, Tai PC, Wang B Design, synthesis and biological evaluation of rose bengal analogues as SecA inhibitors. ChemMedChem. 2013 Aug; 8(8):1384-93. doi:10.1002/cmdc.201300216. PMID:23794293
Auclair SM, Oliver DB, Mukerji I Defining the solution state dimer structure of Escherichia coli SecA using Förster resonance energy transfer. Biochemistry. 2013 Apr 09; 52(14):2388-401. doi:10.1021/bi301217t. PMID:23484952
Kim DM, Zheng H, Huang YJ, Montelione GT, Hunt JF ATPase active-site electrostatic interactions control the global conformation of the 100 kDa SecA translocase. Journal of the American Chemical Society. 2013 Feb 27; 135(8):2999-3010. doi:10.1021/ja306361q. PMID:23167435
Huang YJ, Wang H, Gao FB, Li M, Yang H, Wang B, Tai PC Fluorescein analogues inhibit SecA ATPase: the first sub-micromolar inhibitor of bacterial protein translocation. ChemMedChem. 2012 Apr; 7(4):571-7. doi:10.1002/cmdc.201100594. PMID:22354575
Kakeshita H, Kakeshtia H, Kageyama Y, Ara K, Ozaki K, Nakamura K Enhanced extracellular production of heterologous proteins in Bacillus subtilis by deleting the C-terminal region of the SecA secretory machinery. Molecular biotechnology. 2010 Nov; 46(3):250-7. doi:10.1007/s12033-010-9295-0. PMID:20574771
Bauer BW, Rapoport TA Mapping polypeptide interactions of the SecA ATPase during translocation. Proceedings of the National Academy of Sciences of the United States of America. 2009 Dec 08; 106(49):20800-5. doi:10.1073/pnas.0910550106. PMID:19933328
Gouridis G, Karamanou S, Gelis I, Kalodimos CG, Economou A Signal peptides are allosteric activators of the protein translocase. Nature. 2009 Nov 19; 462(7271):363-7. doi:10.1038/nature08559. PMID:19924216
Zimmer J, Rapoport TA Conformational flexibility and peptide interaction of the translocation ATPase SecA. Journal of molecular biology. 2009 Dec 11; 394(4):606-12. doi:10.1016/j.jmb.2009.10.024. PMID:19850053
Zimmer J, Nam Y, Rapoport TA Structure of a complex of the ATPase SecA and the protein-translocation channel. Nature. 2008 Oct 16; 455(7215):936-43. doi:10.1038/nature07335. PMID:18923516
Gerth U, Kock H, Kusters I, Michalik S, Switzer RL, Hecker M Clp-dependent proteolysis down-regulates central metabolic pathways in glucose-starved Bacillus subtilis. Journal of bacteriology. 2008 Jan; 190(1):321-31. . PMID:17981983
Ding H, Hunt JF, Mukerji I, Oliver D Bacillus subtilis SecA ATPase exists as an antiparallel dimer in solution. Biochemistry. 2003 Jul 29; 42(29):8729-38. . PMID:12873133
Hunt JF, Weinkauf S, Henry L, Fak JJ, McNicholas P, Oliver DB, Deisenhofer J Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA. Science (New York, N.Y.). 2002 Sep 20; 297(5589):2018-26. . PMID:12242434
Jongbloed JD, Antelmann H, Hecker M, Nijland R, Bron S, Airaksinen U, Pries F, Quax WJ, van Dijl JM, Braun PG Selective contribution of the twin-arginine translocation pathway to protein secretion in Bacillus subtilis. The Journal of biological chemistry. 2002 Nov 15; 277(46):44068-78. . PMID:12218047
van Wely KH, Swaving J, Klein M, Freudl R, Driessen AJ The carboxyl terminus of the Bacillus subtilis SecA is dispensable for protein secretion and viability. Microbiology (Reading, England). 2000 Oct; 146 ( Pt 10):2573-81. . PMID:11021932
Müller JP, Ozegowski J, Vettermann S, Swaving J, Van Wely KH, Driessen AJ Interaction of Bacillus subtilis CsaA with SecA and precursor proteins. The Biochemical journal. 2000 Jun 01; 348 Pt 2:367-73. . PMID:10816431
Leloup L, Driessen AJ, Freudl R, Chambert R, Petit-Glatron MF Differential dependence of levansucrase and alpha-amylase secretion on SecA (Div) during the exponential phase of growth of Bacillus subtilis. Journal of bacteriology. 1999 Mar; 181(6):1820-6. . PMID:10074074
Herbort M, Klein M, Manting EH, Driessen AJ, Freudl R Temporal expression of the Bacillus subtilis secA gene, encoding a central component of the preprotein translocase. Journal of bacteriology. 1999 Jan; 181(2):493-500. . PMID:9882663
Bunai K, Yamada K, Hayashi K, Nakamura K, Yamane K Enhancing effect of Bacillus subtilis Ffh, a homologue of the SRP54 subunit of the mammalian signal recognition particle, on the binding of SecA to precursors of secretory proteins in vitro. Journal of biochemistry. 1999 Jan; 125(1):151-9. . PMID:9880811
van der Wolk J, Klose M, Breukink E, Demel RA, de Kruijff B, Freudl R, Driessen AJ Characterization of a Bacillus subtilis SecA mutant protein deficient in translocation ATPase and release from the membrane. Molecular microbiology. 1993 Apr; 8(1):31-42. . PMID:8497195
Klose M, Schimz KL, van der Wolk J, Driessen AJ, Freudl R Lysine 106 of the putative catalytic ATP-binding site of the Bacillus subtilis SecA protein is required for functional complementation of Escherichia coli secA mutants in vivo. The Journal of biological chemistry. 1993 Feb 25; 268(6):4504-10. . PMID:8440733
Nakane A, Takamatsu H, Oguro A, Sadaie Y, Nakamura K, Yamane K Acquisition of azide-resistance by elevated SecA ATPase activity confers azide-resistance upon cell growth and protein translocation in Bacillus subtilis. Microbiology (Reading, England). 1995 Jan; 141 ( Pt 1):113-21. . PMID:7894702
Klein M, Hofmann B, Klose M, Freudl R Isolation and characterization of a Bacillus subtilis secA mutant allele conferring resistance to sodium azide. FEMS microbiology letters. 1994 Dec 15; 124(3):393-7. . PMID:7851746
Takamatsu H, Nakane A, Oguro A, Sadaie Y, Nakamura K, Yamane K A truncated Bacillus subtilis SecA protein consisting of the N-terminal 234 amino acid residues forms a complex with Escherichia coli SecA51(ts) protein and complements the protein translocation defect of the secA51 mutant. Journal of biochemistry. 1994 Dec; 116(6):1287-94. . PMID:7706219
van der Wolk JP, Klose M, de Wit JG, den Blaauwen T, Freudl R, Driessen AJ Identification of the magnesium-binding domain of the high-affinity ATP-binding site of the Bacillus subtilis and Escherichia coli SecA protein. The Journal of biological chemistry. 1995 Aug 11; 270(32):18975-82. . PMID:7642557
Takamatsu H, Fuma S, Nakamura K, Sadaie Y, Shinkai A, Matsuyama S, Mizushima S, Yamane K In vivo and in vitro characterization of the secA gene product of Bacillus subtilis. Journal of bacteriology. 1992 Jul; 174(13):4308-16. . PMID:1385592