EXSA_PSEAE
ID EXSA_PSEAE Reviewed; 278 AA.
AC P26993;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 08-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=HTH-type transcriptional regulator ExsA {ECO:0000303|PubMed:26317977};
GN Name=exsA; OrderedLocusNames=PA1713;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=1655713; DOI=10.1128/jb.173.20.6460-6468.1991;
RA Frank D.W., Iglewski B.H.;
RT "Cloning and sequence analysis of a trans-regulatory locus required for
RT exoenzyme S synthesis in Pseudomonas aeruginosa.";
RL J. Bacteriol. 173:6460-6468(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [3]
RP ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RX PubMed=15225323; DOI=10.1111/j.1365-2958.2004.04128.x;
RA Dasgupta N., Lykken G.L., Wolfgang M.C., Yahr T.L.;
RT "A novel anti-anti-activator mechanism regulates expression of the
RT Pseudomonas aeruginosa type III secretion system.";
RL Mol. Microbiol. 53:297-308(2004).
RN [4]
RP ACTIVITY REGULATION, AND INTERACTION WITH EXSD.
RX PubMed=19369699; DOI=10.1074/jbc.m109.003533;
RA Thibault J., Faudry E., Ebel C., Attree I., Elsen S.;
RT "Anti-activator ExsD forms a 1:1 complex with ExsA to inhibit transcription
RT of type III secretion operons.";
RL J. Biol. Chem. 284:15762-15770(2009).
RN [5]
RP ACTIVITY REGULATION, AND INTERACTION WITH EXSD.
RX PubMed=20008065; DOI=10.1128/jb.01457-09;
RA Brutinel E.D., Vakulskas C.A., Yahr T.L.;
RT "ExsD inhibits expression of the Pseudomonas aeruginosa type III secretion
RT system by disrupting ExsA self-association and DNA binding activity.";
RL J. Bacteriol. 192:1479-1486(2010).
RN [6]
RP INDUCTION BY VRF.
RX PubMed=26929300; DOI=10.1128/jb.00049-16;
RA Marsden A.E., Intile P.J., Schulmeyer K.H., Simmons-Patterson E.R.,
RA Urbanowski M.L., Wolfgang M.C., Yahr T.L.;
RT "Vfr Directly Activates exsA Transcription To Regulate Expression of the
RT Pseudomonas aeruginosa Type III Secretion System.";
RL J. Bacteriol. 198:1442-1450(2016).
RN [7]
RP FUNCTION, AND DNA-BINDING.
RC STRAIN=PAK;
RX PubMed=31527124; DOI=10.1128/iai.00695-19;
RA Tian Z., Cheng S., Xia B., Jin Y., Bai F., Cheng Z., Jin S., Liu X., Wu W.;
RT "Pseudomonas aeruginosa ExsA Regulates a Metalloprotease, ImpA, That
RT Inhibits Phagocytosis of Macrophages.";
RL Infect. Immun. 87:0-0(2019).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-178, SUBUNIT, FUNCTION, AND
RP MUTAGENESIS OF LEU-117.
RX PubMed=26317977; DOI=10.1371/journal.pone.0136533;
RA Shrestha M., Xiao Y., Robinson H., Schubot F.D.;
RT "Structural Analysis of the Regulatory Domain of ExsA, a Key
RT Transcriptional Regulator of the Type Three Secretion System in Pseudomonas
RT aeruginosa.";
RL PLoS ONE 10:e0136533-e0136533(2015).
CC -!- FUNCTION: Transcriptional regulator that plays an essential role in the
CC activation the type III secretion system (T3SS) operons
CC (PubMed:1655713, PubMed:26317977). In addition, ExsA directly regulates
CC the transcription of ImpA virulence factor that cooperatively inhibits
CC the functions of host macrophages together with the T3SS
CC (PubMed:31527124). {ECO:0000269|PubMed:1655713,
CC ECO:0000269|PubMed:26317977, ECO:0000269|PubMed:31527124}.
CC -!- ACTIVITY REGULATION: In the absence of inducing signals such as low
CC Ca(2+) or host cell contact, the T3SS/injectisome is expressed at a low
CC basal level and exists in a quiescent state due to ExsA sequestration
CC by ExsD in a 1:1 complex (PubMed:19369699, PubMed:20008065). Upon host
CC cell contact, this interaction is disrupted by the anti-antiactivator
CC protein ExsC leading to ExsA activation (PubMed:15225323).
CC {ECO:0000269|PubMed:15225323, ECO:0000269|PubMed:19369699,
CC ECO:0000269|PubMed:20008065}.
CC -!- SUBUNIT: Homodimer (PubMed:26317977). Interacts with ExsD; this
CC interaction inhibits ExsA activity (PubMed:19369699, PubMed:20008065).
CC {ECO:0000269|PubMed:19369699, ECO:0000269|PubMed:20008065,
CC ECO:0000269|PubMed:26317977}.
CC -!- INTERACTION:
CC P26993; Q9I321: exsD; NbExp=2; IntAct=EBI-6307207, EBI-6409805;
CC -!- INDUCTION: By cAMP-dependent DNA-binding protein Vfr that directly
CC activates exsA transcription from a promoter located immediately
CC upstream of exsA. {ECO:0000269|PubMed:26929300}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutants are defective in expression and
CC secretion of type III secretion system-related exoproducts.
CC {ECO:0000269|PubMed:15225323}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA25816.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M64975; AAA25816.1; ALT_INIT; Genomic_DNA.
DR EMBL; AE004091; AAG05102.1; -; Genomic_DNA.
DR PIR; A83430; A83430.
DR PIR; C41047; C41047.
DR RefSeq; NP_250404.1; NC_002516.2.
DR RefSeq; WP_003120334.1; NZ_QZGE01000003.1.
DR PDB; 4ZUA; X-ray; 2.50 A; A/B=2-178.
DR PDBsum; 4ZUA; -.
DR AlphaFoldDB; P26993; -.
DR SMR; P26993; -.
DR IntAct; P26993; 1.
DR MINT; P26993; -.
DR STRING; 287.DR97_174; -.
DR BindingDB; P26993; -.
DR ChEMBL; CHEMBL1075205; -.
DR PaxDb; P26993; -.
DR PRIDE; P26993; -.
DR DNASU; 879712; -.
DR EnsemblBacteria; AAG05102; AAG05102; PA1713.
DR GeneID; 879712; -.
DR KEGG; pae:PA1713; -.
DR PATRIC; fig|208964.12.peg.1775; -.
DR PseudoCAP; PA1713; -.
DR HOGENOM; CLU_073843_2_0_6; -.
DR InParanoid; P26993; -.
DR OMA; ISMEAGF; -.
DR PhylomeDB; P26993; -.
DR BioCyc; PAER208964:G1FZ6-1744-MON; -.
DR PHI-base; PHI:6399; -.
DR PHI-base; PHI:6992; -.
DR PHI-base; PHI:8765; -.
DR PRO; PR:P26993; -.
DR Proteomes; UP000002438; Chromosome.
DR CollecTF; EXPREG_000009f0; -.
DR GO; GO:0032993; C:protein-DNA complex; IMP:CollecTF.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IMP:CollecTF.
DR GO; GO:0043565; F:sequence-specific DNA binding; IMP:CollecTF.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:CollecTF.
DR GO; GO:0050709; P:negative regulation of protein secretion; IMP:PseudoCAP.
DR GO; GO:2000144; P:positive regulation of DNA-templated transcription, initiation; IDA:CACAO.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:PseudoCAP.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR018060; HTH_AraC.
DR InterPro; IPR018062; HTH_AraC-typ_CS.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR020449; Tscrpt_reg_HTH_AraC-type.
DR Pfam; PF12833; HTH_18; 1.
DR PRINTS; PR00032; HTHARAC.
DR SMART; SM00342; HTH_ARAC; 1.
DR SUPFAM; SSF46689; SSF46689; 2.
DR PROSITE; PS00041; HTH_ARAC_FAMILY_1; 1.
DR PROSITE; PS01124; HTH_ARAC_FAMILY_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..278
FT /note="HTH-type transcriptional regulator ExsA"
FT /id="PRO_0000194511"
FT DOMAIN 171..269
FT /note="HTH araC/xylS-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT DNA_BIND 188..209
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT DNA_BIND 236..259
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT MUTAGEN 117
FT /note="L->R: More than 90% attenuated transcriptional
FT activation."
FT /evidence="ECO:0000269|PubMed:26317977"
FT CONFLICT 94..95
FT /note="AL -> RV (in Ref. 1; AAA25816)"
FT /evidence="ECO:0000305"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 23..38
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:4ZUA"
FT HELIX 82..96
FT /evidence="ECO:0007829|PDB:4ZUA"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:4ZUA"
FT HELIX 116..130
FT /evidence="ECO:0007829|PDB:4ZUA"
FT HELIX 136..151
FT /evidence="ECO:0007829|PDB:4ZUA"
FT HELIX 155..164
FT /evidence="ECO:0007829|PDB:4ZUA"
SQ SEQUENCE 278 AA; 31642 MW; 4823D0E9135E0BB7 CRC64;
MQGAKSLGRK QITSCHWNIP TFEYRVNKEE GVYVLLEGEL TVQDIDSTFC LAPGELLFVR
RGSYVVSTKG KDSRILWIPL SAQFLQGFVQ RFGALLSEVE RCDEPVPGII AFAATPLLAG
CVKGLKELLV HEHPPMLACL KIEELLMLFA FSPQGPLLMS VLRQLSNRHV ERLQLFMEKH
YLNEWKLSDF SREFGMGLTT FKELFGSVYG VSPRAWISER RILYAHQLLL NSDMSIVDIA
MEAGFSSQSY FTQSYRRRFG CTPSRSRQGK DECRAKNN
