ID   SARA_SALT1              Reviewed;         181 AA.
AC   A0A0F6B506;
DT   16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT   24-JUN-2015, sequence version 1.
DT   03-AUG-2022, entry version 22.
DE   RecName: Full=Salmonella anti-inflammatory response activator {ECO:0000303|PubMed:29924996};
DE            Short=SarA {ECO:0000303|PubMed:29924996};
DE   AltName: Full=Salmonella translocated effector E {ECO:0000303|PubMed:20974834};
GN   Name=sarA {ECO:0000303|PubMed:29924996};
GN   Synonyms=gogC {ECO:0000303|PubMed:11136448},
GN   pagJ {ECO:0000303|PubMed:15813739}, steE {ECO:0000303|PubMed:20974834},
GN   stm2585 {ECO:0000303|PubMed:29924996}; OrderedLocusNames=STM14_3166;
OS   Salmonella typhimurium (strain 14028s / SGSC 2262).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Salmonella.
OX   NCBI_TaxID=588858;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=14028s / SGSC 2262;
RX   PubMed=19897643; DOI=10.1128/jb.01233-09;
RA   Jarvik T., Smillie C., Groisman E.A., Ochman H.;
RT   "Short-term signatures of evolutionary change in the Salmonella enterica
RT   serovar typhimurium 14028 genome.";
RL   J. Bacteriol. 192:560-567(2010).
RN   [2]
RP   GENE NAME.
RC   STRAIN=14028s / SGSC 2262;
RX   PubMed=11136448; DOI=10.1046/j.1365-2958.2001.02234.x;
RA   Figueroa-Bossi N., Uzzau S., Maloriol D., Bossi L.;
RT   "Variable assortment of prophages provides a transferable repertoire of
RT   pathogenic determinants in Salmonella.";
RL   Mol. Microbiol. 39:260-271(2001).
RN   [3]
RP   INDUCTION.
RC   STRAIN=14028s / SGSC 2262;
RX   PubMed=11742086; DOI=10.1073/pnas.261348198;
RA   Uzzau S., Figueroa-Bossi N., Rubino S., Bossi L.;
RT   "Epitope tagging of chromosomal genes in Salmonella.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:15264-15269(2001).
RN   [4]
RP   INDUCTION.
RC   STRAIN=14028s / SGSC 2262;
RX   PubMed=15813739; DOI=10.1111/j.1365-2958.2005.04553.x;
RA   Navarre W.W., Halsey T.A., Walthers D., Frye J., McClelland M.,
RA   Potter J.L., Kenney L.J., Gunn J.S., Fang F.C., Libby S.J.;
RT   "Co-regulation of Salmonella enterica genes required for virulence and
RT   resistance to antimicrobial peptides by SlyA and PhoP/PhoQ.";
RL   Mol. Microbiol. 56:492-508(2005).
RN   [5]
RP   SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023;
RX   PubMed=20974834; DOI=10.1128/iai.00771-10;
RA   Niemann G.S., Brown R.N., Gustin J.K., Stufkens A., Shaikh-Kidwai A.S.,
RA   Li J., McDermott J.E., Brewer H.M., Schepmoes A., Smith R.D., Adkins J.N.,
RA   Heffron F.;
RT   "Discovery of novel secreted virulence factors from Salmonella enterica
RT   serovar Typhimurium by proteomic analysis of culture supernatants.";
RL   Infect. Immun. 79:33-43(2011).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023;
RX   PubMed=24019407; DOI=10.1128/iai.00874-13;
RA   Elfenbein J.R., Endicott-Yazdani T., Porwollik S., Bogomolnaya L.M.,
RA   Cheng P., Guo J., Zheng Y., Yang H.J., Talamantes M., Shields C., Maple A.,
RA   Ragoza Y., DeAtley K., Tatsch T., Cui P., Andrews K.D., McClelland M.,
RA   Lawhon S.D., Andrews-Polymenis H.;
RT   "Novel determinants of intestinal colonization of Salmonella enterica
RT   serotype typhimurium identified in bovine enteric infection.";
RL   Infect. Immun. 81:4311-4320(2013).
RN   [7]
RP   FUNCTION, INTERACTION WITH HUMAN STAT3, SUBCELLULAR LOCATION, AND
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=14028s / SGSC 2262;
RX   PubMed=29924996; DOI=10.1016/j.celrep.2018.05.072;
RA   Jaslow S.L., Gibbs K.D., Fricke W.F., Wang L., Pittman K.J., Mammel M.K.,
RA   Thaden J.T., Fowler V.G. Jr., Hammer G.E., Elfenbein J.R., Ko D.C.;
RT   "Salmonella Activation of STAT3 Signaling by SarA Effector Promotes
RT   Intracellular Replication and Production of IL-10.";
RL   Cell Rep. 23:3525-3536(2018).
CC   -!- FUNCTION: A Salmonella strain-specific effector that induces a host
CC       STAT3-dependent anti-inflammatory pathway. In bacteria-infected host
CC       cells (human) leads to phosphorylation of host STAT3, at least on 'Tyr-
CC       705' and interleukin-10 (IL-10, IL10) production; expressing the gene
CC       alone in host cells induces STAT3 phosphorylation and IL-10 production.
CC       IL-10 production requires STAT3 in infected cells. Contributes to
CC       virulence in mouse infection models (PubMed:29924996). Encoded in only
CC       a few S.typhimurium serovars, it may be a specific effector for
CC       adaptation to bovine hosts (Probable). {ECO:0000269|PubMed:29924996,
CC       ECO:0000305|PubMed:29924996}.
CC   -!- SUBUNIT: Interacts with host (human) STAT3.
CC       {ECO:0000269|PubMed:29924996}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}. Host cytoplasm {ECO:0000269|PubMed:20974834,
CC       ECO:0000269|PubMed:29924996}. Note=Secreted mainly by the SPI-2 type
CC       III secretion system (T3SS), with a minor contribution from the SPI-1
CC       T3SS. {ECO:0000269|PubMed:20974834, ECO:0000269|PubMed:29924996}.
CC   -!- INDUCTION: Expressed during normal cell growth and in bacteria growing
CC       in a human cell line (at protein level) (PubMed:11742086).
CC       Transcription activated by SlyA, which is dependent on PhoP.
CC       {ECO:0000269|PubMed:11742086, ECO:0000269|PubMed:15813739}.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype in a 12 hour, calf ligated
CC       ileal loop infection model (PubMed:24019407). No bacterial growth
CC       phenotype; bacteria no longer induce IL-10 induction in human B cell
CC       lines. Bacteria grow slightly less well in human cell lines 24 hours
CC       post-infection. Deletion leads to greatly decreased phosphorylation of
CC       STAT3 in infected human cells. In mouse infections (C57BL/6 and CBA/J
CC       mice) deletion mutant bacteria are less virulent and less competitive
CC       with wild-type bacteria, mice have a reduced bacterial burden following
CC       intraperitoneal or oral infection, while mouse STAT3 is less
CC       phosphorylated (PubMed:29924996). {ECO:0000269|PubMed:24019407,
CC       ECO:0000269|PubMed:29924996}.
CC   -!- MISCELLANEOUS: Encoded by the Gifsy-1 prophage.
CC       {ECO:0000269|PubMed:11136448}.
CC   -!- MISCELLANEOUS: Also called pagJ, but this gene name had been previously
CC       given to a different gene (AC O30647). {ECO:0000305,
CC       ECO:0000305|PubMed:15813739}.
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DR   EMBL; CP001363; ACY89597.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0F6B506; -.
DR   EnsemblBacteria; ACY89597; ACY89597; STM14_3166.
DR   KEGG; seo:STM14_3166; -.
DR   HOGENOM; CLU_128668_0_0_6; -.
DR   OMA; ANIKACA; -.
DR   BioCyc; SENT588858:STM14_RS26100-MON; -.
DR   Proteomes; UP000002695; Chromosome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Host cytoplasm; Membrane; Transmembrane; Transmembrane helix; Virulence.
FT   CHAIN           1..181
FT                   /note="Salmonella anti-inflammatory response activator"
FT                   /id="PRO_0000448231"
FT   TRANSMEM        4..24
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   181 AA;  20006 MW;  D50C648CDE585948 CRC64;
     MMRFVYIYIL VIYGSYLWFS LGGNMFTINS TNRVASTIAP YACVSDVNLE DKATFLDEHT
     SIHANDSSLQ CFVLNDQHVP QNTLATDVEG YNRGLQERIS LEYQPLESIV FLLGTPAVLE
     TKESLSLPVS PDALTQKLLS ISSNDECKLS GSTSCTTPAS HNPPSGYIAQ YRHSAEVFPD
     E