SETA_LEGPH
ID SETA_LEGPH Reviewed; 644 AA.
AC Q5ZU30;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 25-MAY-2022, entry version 67.
DE RecName: Full=Subversion of eukaryotic traffic protein A;
DE AltName: Full=Effector protein SetA;
DE AltName: Full=Subversion of eukaryotic vesicle trafficking A;
DE Includes:
DE RecName: Full=Glucosyltransferase;
DE EC=2.4.1.-;
DE Includes:
DE RecName: Full=Phosphatidylinositol-3-phosphate-binding domain;
DE AltName: Full=PtdIns(3)P-binding domain;
GN Name=setA; OrderedLocusNames=lpg1978;
OS Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC
OS 33152 / DSM 7513).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales;
OC Legionellaceae; Legionella.
OX NCBI_TaxID=272624;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=15448271; DOI=10.1126/science.1099776;
RA Chien M., Morozova I., Shi S., Sheng H., Chen J., Gomez S.M., Asamani G.,
RA Hill K., Nuara J., Feder M., Rineer J., Greenberg J.J., Steshenko V.,
RA Park S.H., Zhao B., Teplitskaya E., Edwards J.R., Pampou S., Georghiou A.,
RA Chou I.-C., Iannuccilli W., Ulz M.E., Kim D.H., Geringer-Sameth A.,
RA Goldsberry C., Morozov P., Fischer S.G., Segal G., Qu X., Rzhetsky A.,
RA Zhang P., Cayanis E., De Jong P.J., Ju J., Kalachikov S., Shuman H.A.,
RA Russo J.J.;
RT "The genomic sequence of the accidental pathogen Legionella pneumophila.";
RL Science 305:1966-1968(2004).
RN [2]
RP FUNCTION, GENE NAME, SECRETION VIA TYPE IV SECRETION SYSTEM, SUBCELLULAR
RP LOCATION, INDUCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF 134-ASP--ASP-136,
RP AND UBIQUITINATION.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=19016775; DOI=10.1111/j.1462-5822.2008.01249.x;
RA Heidtman M., Chen E.J., Moy M.Y., Isberg R.R.;
RT "Large-scale identification of Legionella pneumophila Dot/Icm substrates
RT that modulate host cell vesicle trafficking pathways.";
RL Cell. Microbiol. 11:230-248(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, SUBCELLULAR LOCATION,
RP PTDINS(3)P-BINDING, AND MUTAGENESIS OF 134-ASP--ASP-136.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=22288428; DOI=10.1111/j.1462-5822.2012.01761.x;
RA Jank T., Bohmer K.E., Tzivelekidis T., Schwan C., Belyi Y., Aktories K.;
RT "Domain organization of Legionella effector SetA.";
RL Cell. Microbiol. 14:852-868(2012).
CC -!- FUNCTION: Secreted effector that interferes with vesicular trafficking
CC of host cells. Possesses glucohydrolase and mono-O-glucosyltransferase
CC activity by using UDP-glucose as a sugar donor substrate. Is able to
CC glucosylate histones H4 and H3.1 in vitro, but it is unlikely that
CC histones are the natural substrates for SetA. May glycosylate a
CC component of the host cell vesicle trafficking machinery during
CC L.pneumophila infection. Binds with high specificity to
CC phosphatidylinositol 3-phosphate (PtdIns(3)P), (with a dissociation
CC constant value of 809 nM), which guides SetA to the cytosolic leaflet
CC of the early phagosome of the host cell. {ECO:0000269|PubMed:19016775,
CC ECO:0000269|PubMed:22288428}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19016775,
CC ECO:0000269|PubMed:22288428}. Note=Is secreted by the Dot/Icm type IV
CC secretion system (T4SS) into the host cell cytosol. Localizes to
CC vesicular compartments in mammalian cells, more precisely to early
CC endosomes and early Legionella-containing phagosomes. After
CC translocation by the Dot/Icm system, a portion of SetA associates with
CC host cell membranes while another portion of SetA remains in the host
CC cell cytosol.
CC -!- INDUCTION: Is induced in the post-exponential phase of growth.
CC {ECO:0000269|PubMed:19016775}.
CC -!- DOMAIN: Multidomain protein with an N-terminal glucosyltransferase
CC domain and a C-terminal phosphatidylinositol 3-phosphate-binding
CC domain, which guides the Legionella effector to the surface of the
CC Legionella-containing vacuole. Both domains are essential for the
CC cellular effects on the eukaryotic host. {ECO:0000269|PubMed:22288428}.
CC -!- PTM: Ubiquitinated and polyubiquitinated when ectopically produced in
CC both yeast and mammalian cells; however it is unsure if this
CC modification occurs during the L.pneumophila infection of host cells.
CC {ECO:0000269|PubMed:19016775}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene grow similarly to wild-
CC type L.pneumophila in both murine bone marrow-derived macrophages and
CC the soil amoeba Dictyostelium discoideum, indicating that SetA is not
CC required for efficient intracellular replication of L.pneumophila in
CC host cells under laboratory growth conditions.
CC {ECO:0000269|PubMed:19016775}.
CC -!- MISCELLANEOUS: Production of SetA in yeast is extremely toxic, it
CC causes a severe growth defect and alters yeast cell morphology. When
CC expressed in mammalian cells, SetA causes cell retractation.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE017354; AAU28047.1; -; Genomic_DNA.
DR RefSeq; WP_010947694.1; NC_002942.5.
DR RefSeq; YP_095994.1; NC_002942.5.
DR AlphaFoldDB; Q5ZU30; -.
DR SMR; Q5ZU30; -.
DR STRING; 272624.lpg1978; -.
DR PaxDb; Q5ZU30; -.
DR DNASU; 3078498; -.
DR EnsemblBacteria; AAU28047; AAU28047; lpg1978.
DR GeneID; 66491110; -.
DR KEGG; lpn:lpg1978; -.
DR PATRIC; fig|272624.6.peg.2071; -.
DR eggNOG; COG3774; Bacteria.
DR HOGENOM; CLU_433330_0_0_6; -.
DR OMA; SEMEAIH; -.
DR Proteomes; UP000000609; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016757; F:glycosyltransferase activity; IEA:UniProtKB-KW.
DR InterPro; IPR007577; GlycoTrfase_DXD_sugar-bd_CS.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF04488; Gly_transf_sug; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Glycosyltransferase; Reference proteome; Secreted; Transferase;
KW Ubl conjugation; Virulence.
FT CHAIN 1..644
FT /note="Subversion of eukaryotic traffic protein A"
FT /id="PRO_0000422423"
FT REGION 1..400
FT /note="Glucosyltransferase"
FT REGION 401..644
FT /note="PtdIns(3)P-binding and localization domain"
FT MUTAGEN 134..136
FT /note="DSD->ASA: Alleviates the toxicity of SetA to host
FT cell growth, and blocks vesicular sorting defects."
FT /evidence="ECO:0000269|PubMed:19016775,
FT ECO:0000269|PubMed:22288428"
FT MUTAGEN 134..136
FT /note="DSD->NSN: Abolishes glucohydrolase and
FT glucosyltransferase activities. Fails to induce any
FT cellular alterations when expressed in mammalian cells."
FT /evidence="ECO:0000269|PubMed:19016775,
FT ECO:0000269|PubMed:22288428"
SQ SEQUENCE 644 AA; 73129 MW; 7D87DA7DB80EC013 CRC64;
MYKIYSYLGW RIDMKTENLP QAGQEAQIDK KIHFIWVGHI MPQKNIQVVS EWAEKNPGYE
TIIWVDKKIA PAKELDLFIL DMKSKGITVK DINEEGVCRD SIRHELDQES PNYGMVSDML
RLNILAAEGG IYLDSDILCS APFPDEIYAP FGFLLSPWSQ GANNTLCNDI ILCSKGNQII
QQLADAIEQS YIARDSFEFT HEYASMKETK GERIAKTLGV TGPGFLFHQL KKMGILNDKS
EMEAIHWELQ DQRYLIDGSV KEPDYFYVPQ NNTNDASWVP SIKRPGIENM SFQERLENAV
QLIAFDIQKT GLFNLDHYAN ELKVKQNSWC IAAETSPELK PDSYLLIRPR DKTGEWTLYY
VDEDKKLNPV TLPVIKGAIK LSEVSDPLRK FHTLLSQVSD PVNPTAHELK QIGRALIELK
PRQDEWHCKN KWSGAEEIAQ ELWQRITSNE TLRAQIKQCF TQFESLKPRV AELGLTRASG
AGTEVEAHES TVKEQEIISQ NTVGEEGTKE KNSVQLASEN SSDEKIKTAH DLIDEIIQDV
IQLDGKLGLL GGNTRQLEDG RVINIPNGAA MIFDDYKKYK QGELTAESAL ESMIKIAKLS
NQLNRHTFFN QRQPETGQFY KKVAAIDLQT TIAAEYDNNH GLRI
