SSEK3_SALTS
ID SSEK3_SALTS Reviewed; 335 AA.
AC P0DUJ7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=Protein-arginine N-acetylglucosaminyltransferase SseK3 {ECO:0000305};
DE Short=Arginine GlcNAcyltransferase SseK3 {ECO:0000305};
DE EC=2.4.1.- {ECO:0000269|PubMed:28069818, ECO:0000269|PubMed:29449376, ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32504010, ECO:0000269|PubMed:32766249, ECO:0000269|PubMed:32974215};
DE AltName: Full=Salmonella secreted effector K3 {ECO:0000303|PubMed:21445262};
GN Name=sseK3 {ECO:0000303|PubMed:21445262, ECO:0000303|PubMed:29449376};
GN OrderedLocusNames=SL1344_1928 {ECO:0000312|EMBL:CBW18025.1};
OS Salmonella typhimurium (strain SL1344).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=216597;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SL1344;
RX PubMed=22538806; DOI=10.1073/pnas.1201061109;
RA Kroger C., Dillon S.C., Cameron A.D., Papenfort K., Sivasankaran S.K.,
RA Hokamp K., Chao Y., Sittka A., Hebrard M., Handler K., Colgan A.,
RA Leekitcharoenphon P., Langridge G.C., Lohan A.J., Loftus B., Lucchini S.,
RA Ussery D.W., Dorman C.J., Thomson N.R., Vogel J., Hinton J.C.;
RT "The transcriptional landscape and small RNAs of Salmonella enterica
RT serovar Typhimurium.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E1277-E1286(2012).
RN [2]
RP SUBCELLULAR LOCATION.
RC STRAIN=SL1344;
RX PubMed=21445262; DOI=10.1371/journal.pone.0017824;
RA Brown N.F., Coombes B.K., Bishop J.L., Wickham M.E., Lowden M.J.,
RA Gal-Mor O., Goode D.L., Boyle E.C., Sanderson K.L., Finlay B.B.;
RT "Salmonella phage ST64B encodes a member of the SseK/NleB effector
RT family.";
RL PLoS ONE 6:e17824-e17824(2011).
RN [3]
RP FUNCTION, INTERACTION WITH HOST TRIM32, AND SUBCELLULAR LOCATION.
RC STRAIN=SL1344;
RX PubMed=26394407; DOI=10.1371/journal.pone.0138529;
RA Yang Z., Soderholm A., Lung T.W., Giogha C., Hill M.M., Brown N.F.,
RA Hartland E., Teasdale R.D.;
RT "SseK3 is a Salmonella effector that binds TRIM32 and modulates the host's
RT NF-kappaB signalling activity.";
RL PLoS ONE 10:e0138529-e0138529(2015).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=28069818; DOI=10.1128/iai.00010-17;
RA Guenster R.A., Matthews S.A., Holden D.W., Thurston T.L.M.;
RT "SseK1 and SseK3 type III secretion system effectors inhibit NF-kappaB
RT signaling and necroptotic cell death in salmonella-infected macrophages.";
RL Infect. Immun. 85:0-0(2017).
RN [5]
RP FUNCTION.
RC STRAIN=SL1344;
RX PubMed=28522607; DOI=10.1074/jbc.m117.790675;
RA El Qaidi S., Chen K., Halim A., Siukstaite L., Rueter C.,
RA Hurtado-Guerrero R., Clausen H., Hardwidge P.R.;
RT "NleB/SseK effectors from Citrobacter rodentium, Escherichia coli, and
RT Salmonella enterica display distinct differences in host substrate
RT specificity.";
RL J. Biol. Chem. 292:11423-11430(2017).
RN [6]
RP DISRUPTION PHENOTYPE.
RC STRAIN=SL1344;
RX PubMed=32517648; DOI=10.1186/s12866-020-01838-z;
RA Yu C., Du F., Zhang C., Li Y., Liao C., He L., Cheng X., Zhang X.;
RT "Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and
RT enhances glycolysis in macrophages.";
RL BMC Microbiol. 20:151-151(2020).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 87-LYS--ARG-89 AND LYS-234.
RC STRAIN=SL1344;
RX PubMed=32504010; DOI=10.1038/s42003-020-1005-2;
RA Meng K., Zhuang X., Peng T., Hu S., Yang J., Wang Z., Fu J., Xue J.,
RA Pan X., Lv J., Liu X., Shao F., Li S.;
RT "Arginine GlcNAcylation of Rab small GTPases by the pathogen Salmonella
RT Typhimurium.";
RL Commun. Biol. 3:287-287(2020).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AUTOGLYCOSYLATION,
RP GLYCOSYLATION AT ARG-153; ARG-184; ARG-305 AND ARG-335, AND MUTAGENESIS OF
RP ARG-153; ARG-184; ARG-305 AND ARG-335.
RC STRAIN=SL1344;
RX PubMed=32432056; DOI=10.3389/fcimb.2020.00197;
RA Xue J., Pan X., Peng T., Duan M., Du L., Zhuang X., Cai X., Yi X., Fu Y.,
RA Li S.;
RT "Auto arginine-GlcNAcylation is crucial for bacterial pathogens in
RT regulating host cell death.";
RL Front. Cell. Infect. Microbiol. 10:197-197(2020).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 226-ASP--ASP-228.
RC STRAIN=SL1344;
RX PubMed=32974215; DOI=10.3389/fcimb.2020.00419;
RA Gan J., Scott N.E., Newson J.P.M., Wibawa R.R., Wong Fok Lung T.,
RA Pollock G.L., Ng G.Z., van Driel I., Pearson J.S., Hartland E.L.,
RA Giogha C.;
RT "The Salmonella effector SseK3 targets small Rab GTPases.";
RL Front. Cell. Infect. Microbiol. 10:419-419(2020).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=SL1344;
RX PubMed=32766249; DOI=10.3389/fcell.2020.00641;
RA Xue J., Hu S., Huang Y., Zhang Q., Yi X., Pan X., Li S.;
RT "Arg-GlcNAcylation on TRADD by NleB and SseK1 is crucial for bacterial
RT pathogenesis.";
RL Front. Cell Dev. Biol. 8:641-641(2020).
RN [11] {ECO:0007744|PDB:6EYR, ECO:0007744|PDB:6EYT}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 14-333 IN COMPLEX WITH
RP URIDINE-5'-DIPHOSPHATE AND MANGANESE, FUNCTION, CATALYTIC ACTIVITY, ACTIVE
RP SITE, COFACTOR, DOMAIN, AND MUTAGENESIS OF GLN-51; TRP-52; TYR-224;
RP 226-ASP--ASP-228; HIS-247; LYS-251; GLU-258; ASN-259; TRP-334 AND ARG-335.
RX PubMed=29449376; DOI=10.1074/jbc.ra118.001796;
RA Esposito D., Gunster R.A., Martino L., El Omari K., Wagner A.,
RA Thurston T.L.M., Rittinger K.;
RT "Structural basis for the glycosyltransferase activity of the Salmonella
RT effector SseK3.";
RL J. Biol. Chem. 293:5064-5078(2018).
RN [12] {ECO:0007744|PDB:6CGI, ECO:0007744|PDB:6DUS}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 25-335 IN COMPLEX WITH
RP URIDINE-5'-DIPHOSPHATE AND MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF 226-ASP--ASP-228 AND GLU-258, AND ACTIVE SITE.
RX PubMed=30902834; DOI=10.1074/mcp.ra118.001093;
RA Newson J.P.M., Scott N.E., Yeuk Wah Chung I., Wong Fok Lung T., Giogha C.,
RA Gan J., Wang N., Strugnell R.A., Brown N.F., Cygler M., Pearson J.S.,
RA Hartland E.L.;
RT "Salmonella effectors SseK1 and SseK3 target death domain proteins in the
RT TNF and TRAIL signaling pathways.";
RL Mol. Cell. Proteomics 18:1138-1156(2019).
CC -!- FUNCTION: Protein-arginine N-acetylglucosaminyltransferase effector
CC that disrupts TNF signaling in infected cells, including NF-kappa-B
CC signaling and apoptosis (PubMed:26394407, PubMed:28069818,
CC PubMed:28522607, PubMed:32766249, PubMed:29449376). Acts by catalyzing
CC the transfer of a single N-acetylglucosamine (GlcNAc) to a conserved
CC arginine residue in the death domain of host proteins such as TRADD,
CC TNFRSF1A/TNFR1 and TNFRSF10B/TRAILR2: arginine GlcNAcylation prevents
CC homotypic/heterotypic death domain interactions and assembly of the
CC oligomeric TNF-alpha receptor complex, thereby disrupting TNF signaling
CC (PubMed:28069818, PubMed:32766249, PubMed:29449376, PubMed:30902834).
CC Also acts on host proteins without a death domain: catalyzes arginine
CC GlcNAcylation of host small Rab GTPase (Rab1, Rab5 and Rab11), thereby
CC preventing GTPase activity and leading to impaired host vesicular
CC protein transport (PubMed:32504010, PubMed:32974215). Also mediates
CC auto-GlcNAcylation, which is required for activity toward death domain-
CC containing host target proteins (PubMed:32432056).
CC {ECO:0000269|PubMed:26394407, ECO:0000269|PubMed:28069818,
CC ECO:0000269|PubMed:28522607, ECO:0000269|PubMed:29449376,
CC ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056,
CC ECO:0000269|PubMed:32504010, ECO:0000269|PubMed:32766249,
CC ECO:0000269|PubMed:32974215}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = H(+)
CC + N(omega)-(N-acetyl-beta-D-glucosaminyl)-L-arginyl-[protein] + UDP;
CC Xref=Rhea:RHEA:66632, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:17079,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:167322;
CC Evidence={ECO:0000269|PubMed:28069818, ECO:0000269|PubMed:29449376,
CC ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056,
CC ECO:0000269|PubMed:32504010, ECO:0000269|PubMed:32766249,
CC ECO:0000269|PubMed:32974215};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66633;
CC Evidence={ECO:0000269|PubMed:28069818, ECO:0000269|PubMed:29449376,
CC ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056,
CC ECO:0000269|PubMed:32504010, ECO:0000269|PubMed:32766249,
CC ECO:0000269|PubMed:32974215};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:29449376};
CC -!- SUBUNIT: Interacts with host TRIM32; without mediating its
CC GlcNAcylation. {ECO:0000269|PubMed:26394407}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21445262}. Host
CC Golgi apparatus {ECO:0000269|PubMed:26394407,
CC ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32504010,
CC ECO:0000269|PubMed:32974215}. Note=Secreted via type III secretion
CC system 2 (SPI-2 TTSS) (PubMed:21445262). Localizes to host Golgi
CC apparatus via lipid-binding (PubMed:32504010).
CC {ECO:0000269|PubMed:21445262, ECO:0000269|PubMed:32504010}.
CC -!- DOMAIN: Adopts a GT-A fold and acts as an inverting enzyme that
CC converts the alpha-configuration in the UDP-N-acetyl-alpha-D-
CC glucosamine donor to the beta configuration in the N-linked (GlcNAc)
CC arginine product. {ECO:0000305|PubMed:29449376}.
CC -!- PTM: Auto-glycosylated: arginine GlcNAcylation is required for activity
CC toward death domain-containing host target proteins.
CC {ECO:0000269|PubMed:32432056}.
CC -!- DISRUPTION PHENOTYPE: Decreased apoptosis in infected macrophages,
CC characterized by reduced CASP3, CASP8 ans CASP9 caspase activity.
CC {ECO:0000269|PubMed:32517648}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase NleB family.
CC {ECO:0000305}.
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DR EMBL; FQ312003; CBW18025.1; -; Genomic_DNA.
DR RefSeq; WP_000492926.1; NZ_QASL01000003.1.
DR PDB; 6CGI; X-ray; 2.30 A; A/B/C/D=25-335.
DR PDB; 6DUS; X-ray; 2.60 A; A/B=26-335.
DR PDB; 6EYR; X-ray; 2.20 A; A/B=14-333.
DR PDB; 6EYT; X-ray; 2.21 A; A/B=14-335.
DR PDBsum; 6CGI; -.
DR PDBsum; 6DUS; -.
DR PDBsum; 6EYR; -.
DR PDBsum; 6EYT; -.
DR AlphaFoldDB; P0DUJ7; -.
DR SMR; P0DUJ7; -.
DR KEGG; sey:SL1344_1928; -.
DR Proteomes; UP000008962; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043657; C:host cell; IDA:UniProtKB.
DR GO; GO:0044177; C:host cell Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0106362; F:protein-arginine N-acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0034053; P:modulation by symbiont of host defense-related programmed cell death; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Glycosyltransferase; Host Golgi apparatus;
KW Lipid-binding; Manganese; Metal-binding; Secreted; Toxin; Transferase;
KW Virulence.
FT CHAIN 1..335
FT /note="Protein-arginine N-acetylglucosaminyltransferase
FT SseK3"
FT /id="PRO_0000452601"
FT MOTIF 226..228
FT /note="DXD motif"
FT /evidence="ECO:0000305"
FT ACT_SITE 258
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:30902834"
FT BINDING 51..53
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:29449376,
FT ECO:0000305|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 75
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:29449376,
FT ECO:0000305|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 224..227
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:29449376,
FT ECO:0000305|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 228
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 325
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 327
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 327
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:29449376,
FT ECO:0000305|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT BINDING 332..335
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:29449376,
FT ECO:0000305|PubMed:30902834, ECO:0000312|PDB:6EYT,
FT ECO:0007744|PDB:6DUS"
FT CARBOHYD 153
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT CARBOHYD 184
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT CARBOHYD 305
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT CARBOHYD 335
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 51
FT /note="Q->A: Strongly reduced protein-arginine N-
FT acetylglucosaminyltransferase activity, while retaining
FT ability to inhibit the NF-kappa-B signaling."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 52
FT /note="W->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 87..89
FT /note="KER->AEA: Abolished localization to the host Golgi
FT apparatus; when associated with A-234."
FT /evidence="ECO:0000269|PubMed:32504010"
FT MUTAGEN 153
FT /note="R->A: In 4RA; abolished auto-GlcNAcylation and
FT reduced activity toward death domain-containing host target
FT proteins; when associated with A-184, A-305 and A-335."
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 184
FT /note="R->A: In 4RA; abolished auto-GlcNAcylation and
FT reduced activity toward death domain-containing host target
FT proteins; when associated with A-153, A-305 and A-335."
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 224
FT /note="Y->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 226..228
FT /note="DAD->AAA: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32974215"
FT MUTAGEN 234
FT /note="K->A: Abolished localization to the host Golgi
FT apparatus; when associated with 87-A-A-89."
FT /evidence="ECO:0000269|PubMed:32504010"
FT MUTAGEN 247
FT /note="H->A: Does not affect protein-arginine N-
FT acetylglucosaminyltransferase activity, while retaining
FT ability to inhibit the NF-kappa-B signaling."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 251
FT /note="K->A: Does not affect protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 258
FT /note="E->A,Q: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 259
FT /note="N->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:30902834"
FT MUTAGEN 305
FT /note="R->A: In 4RA; abolished auto-GlcNAcylation and
FT reduced activity toward death domain-containing host target
FT proteins; when associated with A-153, A-184 and A-335."
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 334
FT /note="W->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29449376"
FT MUTAGEN 335
FT /note="R->A: Does not affect protein-arginine N-
FT acetylglucosaminyltransferase activity, but impairs the
FT GlcNAcylation pattern of host target proteins. In 4RA;
FT abolished auto-GlcNAcylation and reduced activity toward
FT death domain-containing host target proteins; when
FT associated with A-153, A-184 and A-305."
FT /evidence="ECO:0000269|PubMed:29449376,
FT ECO:0000269|PubMed:32432056"
SQ SEQUENCE 335 AA; 37890 MW; 2BF80A0FC929E897 CRC64;
MFSRVRGFLS CQNYSHTATP AITLPSSGSA NFAGVEYPLL PLDQHTPLLF QWFERNPSRF
GENQIPIINT QQNPYLNNII NAAIIEKERT IGVLVDGNFS AGQKKALAKL EKQYENIKVI
YNSDLDYSMY DKKLSDIYLE NIAKIEAQPA NVRDEYLLGE IKKSLNEVLK NNPEESLVSS
HDKRLGHVRF DFYRNLFLLK GSNAFLEAGK HGCHHLQPGG GCIYLDADML LTGKLGTLYL
PDGIAVHVSR KGNSMSLENG IIAVNRSEHP ALKKGLEIMH SKPYGDPYID GVCGGLRHYF
NCSIRHNYEE FCNFIEFKHE HIFMDTSSLT ISSWR
