CSRA_BACSU
ID CSRA_BACSU Reviewed; 74 AA.
AC P33911;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Translational regulator CsrA {ECO:0000255|HAMAP-Rule:MF_00167};
GN Name=csrA {ECO:0000255|HAMAP-Rule:MF_00167};
GN Synonyms=sow {ECO:0000303|PubMed:21895793}, yviG;
GN OrderedLocusNames=BSU35370;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2498284; DOI=10.1128/jb.171.6.3095-3101.1989;
RA Mirel D.B., Chamberlin M.J.;
RT "The Bacillus subtilis flagellin gene (hag) is transcribed by the sigma 28
RT form of RNA polymerase.";
RL J. Bacteriol. 171:3095-3101(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RX PubMed=8969505; DOI=10.1099/13500872-142-11-3079;
RA Soldo B., Lazarevic V., Mauel C., Karamata D.;
RT "Sequence of the 305 degrees-307 degrees region of the Bacillus subtilis
RT chromosome.";
RL Microbiology 142:3079-3088(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [4]
RP IDENTIFICATION.
RA Robison K.;
RL Unpublished observations (SEP-1993).
RN [5]
RP FUNCTION IN TRANSLATION REPRESSION, SUBUNIT, INDUCTION, DISRUPTION
RP PHENOTYPE, AND RNA-BINDING.
RC STRAIN=168, and 1A96;
RX PubMed=17555441; DOI=10.1111/j.1365-2958.2007.05765.x;
RA Yakhnin H., Pandit P., Petty T.J., Baker C.S., Romeo T., Babitzke P.;
RT "CsrA of Bacillus subtilis regulates translation initiation of the gene
RT encoding the flagellin protein (hag) by blocking ribosome binding.";
RL Mol. Microbiol. 64:1605-1620(2007).
RN [6]
RP FUNCTION IN TRANSLATION REPRESSION, INTERACTION WITH FLIW, DISRUPTION
RP PHENOTYPE, MUTAGENESIS OF ARG-6; LYS-7; VAL-25; LEU-32; GLY-33; ALA-36 AND
RP GLU-46, AND RNA-BINDING.
RC STRAIN=3610;
RX PubMed=21895793; DOI=10.1111/j.1365-2958.2011.07822.x;
RA Mukherjee S., Yakhnin H., Kysela D., Sokoloski J., Babitzke P.,
RA Kearns D.B.;
RT "CsrA-FliW interaction governs flagellin homeostasis and a checkpoint on
RT flagellar morphogenesis in Bacillus subtilis.";
RL Mol. Microbiol. 82:447-461(2011).
RN [7]
RP DISRUPTION PHENOTYPE.
RC STRAIN=3610;
RX PubMed=23144244; DOI=10.1128/jb.01654-12;
RA Mukherjee S., Babitzke P., Kearns D.B.;
RT "FliW and FliS function independently to control cytoplasmic flagellin
RT levels in Bacillus subtilis.";
RL J. Bacteriol. 195:297-306(2013).
RN [8]
RP FUNCTION, INTERACTION WITH FLIW, DOMAIN, AND MUTAGENESIS OF ARG-6; LYS-7;
RP ILE-14; GLY-33; ALA-36; GLU-46; LEU-49; ASN-55 AND ALA-58.
RC STRAIN=3610;
RX PubMed=27516547; DOI=10.1073/pnas.1602455113;
RA Mukherjee S., Oshiro R.T., Yakhnin H., Babitzke P., Kearns D.B.;
RT "FliW antagonizes CsrA RNA binding by a noncompetitive allosteric
RT mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:9870-9875(2016).
RN [9]
RP REVIEW.
RX PubMed=25833324; DOI=10.1128/mmbr.00052-14;
RA Vakulskas C.A., Potts A.H., Babitzke P., Ahmer B.M., Romeo T.;
RT "Regulation of bacterial virulence by Csr (Rsm) systems.";
RL Microbiol. Mol. Biol. Rev. 79:193-224(2015).
RN [10]
RP STRUCTURE BY NMR.
RA Koharudin L.M.I., Georgiou T., Kleanthous C., Geoffrey R., Kaptein R.,
RA Boelens R.;
RT "A model for RNA binding by the bacterial carbon storage regulatory
RT protein, csrA.";
RL Submitted (OCT-2005) to the PDB data bank.
CC -!- FUNCTION: A translational regulator that binds mRNA to regulate
CC translation initiation and/or mRNA stability. Usually binds in the 5'-
CC UTR at or near the Shine-Dalgarno sequence preventing ribosome-binding,
CC thus repressing translation. Represses expression of flagellin (hag) in
CC a post-transcriptional fashion. Specifically binds to 2 sites in the
CC 5'-UTR of hag mRNA in a cooperative fashion; the second site overlaps
CC the Shine-Dalgarno sequence and prevents 30S ribosomal subunit binding
CC (PubMed:17555441). Mutation of either binding site abolishes CsrA
CC regulation of hag expression (PubMed:17555441, PubMed:21895793).
CC Repression is greater in the 1A96 than 168 genetic background and
CC higher in minimal than rich medium (PubMed:17555441). Translation
CC repression is antagonized by FliW (PubMed:21895793). Partner switching
CC by flagellin between FliW and CsrA provides a flagellar assembly
CC checkpoint to tightly control the timing of flagellin synthesis.
CC Flagellin binds to assembly factor FliW, freeing CsrA to repress
CC translation of the flagellin mRNA. When the flagellar hook is assembled
CC flagellin is secreted, depleting intracellular flagellin, which frees
CC FliW to interact with CsrA and inhibits CsrA binding to mRNA. This
CC derepresses flagellin translation and provides protein for flagellar
CC assembly. Once the flagellar filament is completed cytoplasmic
CC flagellin levels rise and CsrA translation repression of flagellin
CC reinitiates (PubMed:21895793, PubMed:27516547). Overexpression leads to
CC a dramatic reduction in motility, a significant reduction in flagellin
CC synthesis and reduced flagella assembly (PubMed:21895793).
CC {ECO:0000269|PubMed:17555441, ECO:0000269|PubMed:21895793,
CC ECO:0000269|PubMed:27516547}.
CC -!- SUBUNIT: Homodimer (PubMed:17555441). The beta-strands of each monomer
CC intercalate to form a hydrophobic core while the alpha-helices form
CC wings that extend away from the core (By similarity). Two molecules of
CC FliW interact with 1 homodimer (PubMed:21895793, PubMed:27516547). mRNA
CC and FliW bind to different sites on CsrA (PubMed:27516547).
CC {ECO:0000250|UniProtKB:O69078, ECO:0000269|PubMed:21895793,
CC ECO:0000269|PubMed:27516547, ECO:0000305|PubMed:17555441}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00167}.
CC -!- INDUCTION: Part of the SigD-controlled yvyF-csrA operon and the SigA-
CC controlled fliW-csrA operon (PubMed:17555441). Expressed from the SigA
CC operon at low levels during log phase, with a 5-fold increase as the
CC culture transitions to stationary phase, peaking 1 hour later.
CC {ECO:0000269|PubMed:17555441}.
CC -!- DOMAIN: Contacts FliW via its C-terminus (residues 49-58).
CC {ECO:0000269|PubMed:27516547}.
CC -!- DISRUPTION PHENOTYPE: Increased expression of flagellin (hag), 30%
CC decrease in motility halo (PubMed:17555441). Suppresses the motility
CC loss and flagellar assembly defect of an fliW deletion
CC (PubMed:21895793). Suppresses the phenotypes associated with deletion
CC of the intracellular flagella chaperone fliS (PubMed:23144244).
CC {ECO:0000269|PubMed:17555441, ECO:0000269|PubMed:21895793,
CC ECO:0000269|PubMed:23144244}.
CC -!- SIMILARITY: Belongs to the CsrA/RsmA family. {ECO:0000255|HAMAP-
CC Rule:MF_00167}.
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DR EMBL; M26948; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U56901; AAC44950.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB15554.1; -; Genomic_DNA.
DR PIR; H69608; H69608.
DR RefSeq; NP_391417.1; NC_000964.3.
DR RefSeq; WP_003219727.1; NZ_JNCM01000033.1.
DR PDB; 1T3O; NMR; -; A=1-74.
DR PDBsum; 1T3O; -.
DR AlphaFoldDB; P33911; -.
DR SMR; P33911; -.
DR STRING; 224308.BSU35370; -.
DR PaxDb; P33911; -.
DR EnsemblBacteria; CAB15554; CAB15554; BSU_35370.
DR GeneID; 64305294; -.
DR GeneID; 936731; -.
DR KEGG; bsu:BSU35370; -.
DR PATRIC; fig|224308.179.peg.3828; -.
DR eggNOG; COG1551; Bacteria.
DR InParanoid; P33911; -.
DR OMA; IHRKEVY; -.
DR PhylomeDB; P33911; -.
DR BioCyc; BSUB:BSU35370-MON; -.
DR EvolutionaryTrace; P33911; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IBA:GO_Central.
DR GO; GO:0006402; P:mRNA catabolic process; IEA:InterPro.
DR GO; GO:0045947; P:negative regulation of translational initiation; IBA:GO_Central.
DR GO; GO:1902208; P:regulation of bacterial-type flagellum assembly; IEA:UniProtKB-UniRule.
DR GO; GO:0006109; P:regulation of carbohydrate metabolic process; IEA:InterPro.
DR Gene3D; 2.60.40.4380; -; 1.
DR HAMAP; MF_00167; CsrA; 1.
DR InterPro; IPR003751; CsrA.
DR InterPro; IPR036107; CsrA_sf.
DR PANTHER; PTHR34984; PTHR34984; 1.
DR Pfam; PF02599; CsrA; 1.
DR SUPFAM; SSF117130; SSF117130; 1.
DR TIGRFAMs; TIGR00202; csrA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Reference proteome; Repressor; RNA-binding;
KW Translation regulation.
FT CHAIN 1..74
FT /note="Translational regulator CsrA"
FT /id="PRO_0000177049"
FT MUTAGEN 6
FT /note="R->L,W: In sow-2 and sow28; suppresses the motility
FT loss and flagellar assembly defect of an fliW deletion.
FT Binds FliW."
FT /evidence="ECO:0000269|PubMed:21895793,
FT ECO:0000269|PubMed:27516547"
FT MUTAGEN 7
FT /note="K->E: In sow-12; suppresses the motility loss and
FT flagellar assembly defect of an fliW deletion. Binds FliW."
FT /evidence="ECO:0000269|PubMed:21895793,
FT ECO:0000269|PubMed:27516547"
FT MUTAGEN 14
FT /note="I->M: Inhibits motility and flagellar filament
FT assembly, still binds FliW. Binds 5'-UTR of hag mRNA, is
FT not completed by FliW."
FT /evidence="ECO:0000269|PubMed:27516547"
FT MUTAGEN 25
FT /note="V->G: In sow-20; suppresses the motility loss and
FT flagellar assembly defect of an fliW deletion."
FT /evidence="ECO:0000269|PubMed:21895793"
FT MUTAGEN 32
FT /note="L->P: In sow-10; suppresses the motility loss and
FT flagellar assembly defect of an fliW deletion."
FT /evidence="ECO:0000269|PubMed:21895793"
FT MUTAGEN 33
FT /note="G->R: In sow-11; suppresses the motility loss and
FT flagellar assembly defect of an fliW deletion. Binds FliW."
FT /evidence="ECO:0000269|PubMed:21895793,
FT ECO:0000269|PubMed:27516547"
FT MUTAGEN 36
FT /note="A->T,V: In sow-8 and sow-4; suppresses the motility
FT loss and flagellar assembly defect of an fliW deletion.
FT Binds FliW."
FT /evidence="ECO:0000269|PubMed:21895793,
FT ECO:0000269|PubMed:27516547"
FT MUTAGEN 46
FT /note="E->K: In sow-15; suppresses the motility loss and
FT flagellar assembly defect of an fliW deletion. Binds FliW."
FT /evidence="ECO:0000269|PubMed:21895793,
FT ECO:0000269|PubMed:27516547"
FT MUTAGEN 49
FT /note="L->S: Inhibits motility and flagellar filament
FT assembly, reduced binding of FliW."
FT /evidence="ECO:0000269|PubMed:27516547"
FT MUTAGEN 55
FT /note="N->D: Inhibits motility and flagellar filament
FT assembly, greatly reduced binding of FliW. Binds 5'-UTR of
FT hag mRNA, is not completed by FliW."
FT /evidence="ECO:0000269|PubMed:27516547"
FT MUTAGEN 58
FT /note="A->V: Inhibits motility and flagellar filament
FT assembly, reduced binding of FliW."
FT /evidence="ECO:0000269|PubMed:27516547"
FT STRAND 1..5
FT /evidence="ECO:0007829|PDB:1T3O"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:1T3O"
FT TURN 15..17
FT /evidence="ECO:0007829|PDB:1T3O"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:1T3O"
FT STRAND 30..38
FT /evidence="ECO:0007829|PDB:1T3O"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:1T3O"
SQ SEQUENCE 74 AA; 8136 MW; 10E82DA62D3174B5 CRC64;
MLVLSRKINE AIQIGADIEV KVIAVEGDQV KLGIDAPKHI DIHRKEIYLT IQEENNRAAA
LSSDVISALS SQKK
