SSEK1_SALTS
ID SSEK1_SALTS Reviewed; 336 AA.
AC A0A0H3NK84;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Protein-arginine N-acetylglucosaminyltransferase SseK1 {ECO:0000305};
DE Short=Arginine GlcNAcyltransferase SseK1 {ECO:0000305};
DE EC=2.4.1.- {ECO:0000269|PubMed:30327479, ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249};
DE AltName: Full=Salmonella secreted effector K1 {ECO:0000303|PubMed:32432056};
GN Name=sseK1 {ECO:0000303|PubMed:32432056};
GN OrderedLocusNames=SL1344_4096 {ECO:0000312|EMBL:CBW20184.1};
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 DOMAIN.
RC STRAIN=SL1344;
RX PubMed=30463645; DOI=10.5483/bmbrep.2018.51.12.269;
RA Park J.B., Yoo Y., Cho H.S.;
RT "Structural insights showing how arginine is able to be glycosylated by
RT pathogenic effector proteins.";
RL BMB Rep. 51:609-610(2018).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF
RP 223-ASP--ASP-225 AND GLU-255.
RC STRAIN=SL1344;
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).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AUTOGLYCOSYLATION,
RP GLYCOSYLATION AT ARG-24; ARG-152 AND ARG-333, AND MUTAGENESIS OF ARG-24;
RP ARG-152 AND ARG-333.
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 [5]
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 [6] {ECO:0007744|PDB:5H60, ECO:0007744|PDB:6IXK}
RP X-RAY CRYSTALLOGRAPHY (3.64 ANGSTROMS) OF MUTANT SER-39/SER-210 IN COMPLEX
RP WITH URIDINE-5'-DIPHOSPHATE AND MANGANESE, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, DOMAIN, ACTIVE SITE, AND MUTAGENESIS OF CYS-39; TRP-51; PHE-187;
RP CYS-210; HIS-244 AND 255-GLU-ASN-256.
RC STRAIN=SL1344;
RX PubMed=30327479; DOI=10.1038/s41467-018-06680-6;
RA Park J.B., Kim Y.H., Yoo Y., Kim J., Jun S.H., Cho J.W., El Qaidi S.,
RA Walpole S., Monaco S., Garcia-Garcia A.A., Wu M., Hays M.P.,
RA Hurtado-Guerrero R., Angulo J., Hardwidge P.R., Shin J.S., Cho H.S.;
RT "Structural basis for arginine glycosylation of host substrates by
RT bacterial effector proteins.";
RL Nat. Commun. 9:4283-4283(2018).
CC -!- FUNCTION: Protein-arginine N-acetylglucosaminyltransferase effector
CC that disrupts TNF signaling in infected cells, including NF-kappa-B
CC signaling, apoptosis and necroptosis (PubMed:32766249,
CC PubMed:30327479). Acts by catalyzing the transfer of a single N-
CC acetylglucosamine (GlcNAc) to a conserved arginine residue in the death
CC domain of host proteins TRADD and, to a lower extent, FADD: arginine
CC GlcNAcylation prevents homotypic/heterotypic death domain interactions
CC and assembly of the oligomeric TNF-alpha receptor complex, thereby
CC disrupting TNF signaling (PubMed:30902834, PubMed:32766249,
CC PubMed:30327479). Also acts on host proteins without a death domain:
CC catalyzes arginine GlcNAcylation of host GAPDH protein, thereby
CC preventing GAPDH interaction with TRAF2, leading to inhibit NF-kappa-B
CC signaling (By similarity). Catalyzes GlcNAcylation of host tubulin-
CC folding cofactor TBCB, thereby promoting microtubule stability (By
CC similarity). Also mediates auto-GlcNAcylation, which is required for
CC activity toward death domain-containing host target proteins
CC (PubMed:32432056). {ECO:0000250|UniProtKB:Q9L9J3,
CC ECO:0000269|PubMed:30327479, ECO:0000269|PubMed:30902834,
CC ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249}.
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:30327479, ECO:0000269|PubMed:30902834,
CC ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66633;
CC Evidence={ECO:0000269|PubMed:30327479, ECO:0000269|PubMed:30902834,
CC ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:30327479};
CC -!- ACTIVITY REGULATION: Protein-arginine N-acetylglucosaminyltransferase
CC activity is inhibited by 100066N compound (flavone analog) and 102644N
CC compound (a substituted isoxazole). {ECO:0000250|UniProtKB:Q9L9J3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9L9J3}. Host
CC cytoplasm, host cytosol {ECO:0000305|PubMed:32432056}. Note=Secreted
CC via type III secretion systems 1 and 2 (SPI-1 and SPI-2 TTSS).
CC {ECO:0000250|UniProtKB:Q9L9J3}.
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:0000269|PubMed:30327479,
CC ECO:0000269|PubMed:30463645}.
CC -!- PTM: Auto-glycosylated: arginine GlcNAcylation is required for activity
CC toward death domain-containing host target proteins.
CC {ECO:0000269|PubMed:32432056}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase NleB family.
CC {ECO:0000305}.
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DR EMBL; FQ312003; CBW20184.1; -; Genomic_DNA.
DR PDB; 5H60; X-ray; 3.64 A; A=1-336.
DR PDB; 6AGU; X-ray; 3.15 A; A=1-336.
DR PDB; 6IXK; X-ray; 2.20 A; A/B=1-336.
DR PDBsum; 5H60; -.
DR PDBsum; 6AGU; -.
DR PDBsum; 6IXK; -.
DR AlphaFoldDB; A0A0H3NK84; -.
DR SMR; A0A0H3NK84; -.
DR EnsemblBacteria; CBW20184; CBW20184; SL1344_4096.
DR KEGG; sey:SL1344_4096; -.
DR PATRIC; fig|216597.6.peg.4558; -.
DR HOGENOM; CLU_081850_0_0_6; -.
DR OMA; KGHVWFD; -.
DR Proteomes; UP000008962; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Glycosyltransferase; Host cytoplasm; Manganese;
KW Metal-binding; Secreted; Toxin; Transferase; Virulence.
FT CHAIN 1..336
FT /note="Protein-arginine N-acetylglucosaminyltransferase
FT SseK1"
FT /id="PRO_0000452597"
FT MOTIF 223..225
FT /note="DXD motif"
FT /evidence="ECO:0000305"
FT ACT_SITE 255
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0000305|PubMed:30902834"
FT BINDING 50..52
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 74
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 224..225
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 225
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 322
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 324
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 324
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT BINDING 329
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H60"
FT CARBOHYD 24
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT CARBOHYD 152
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT CARBOHYD 333
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 24
FT /note="R->A: In 3RA; abolished auto-GlcNAcylation and
FT reduced activity toward death domain-containing host target
FT proteins; when associated with A-152 and A-333."
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 39
FT /note="C->S: Mutant used for crystallization; prevents
FT protein precipitation due to irregular intermolecular
FT disulfide bonds; when associated with S-210."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 51
FT /note="W->A: Abolished binding to UDP-N-acetyl-alpha-D-
FT glucosamine."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 152
FT /note="R->A: In 3RA; abolished auto-GlcNAcylation and
FT reduced activity toward death domain-containing host target
FT proteins; when associated with A-24 and A-333."
FT /evidence="ECO:0000269|PubMed:32432056"
FT MUTAGEN 187
FT /note="F->A: Reduced binding to UDP-N-acetyl-alpha-D-
FT glucosamine."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 210
FT /note="C->S: Mutant used for crystallization; prevents
FT protein precipitation due to irregular intermolecular
FT disulfide bonds; when associated with S-39."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 223..225
FT /note="DAD->AAA: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30902834"
FT MUTAGEN 244
FT /note="H->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity; when associated
FT with A-255 and 255-A-A-256."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 255..256
FT /note="EN->AA: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity; when associated
FT with A-244."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 255
FT /note="E->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30902834"
FT MUTAGEN 333
FT /note="R->A: In 3RA; abolished auto-GlcNAcylation and
FT reduced activity toward death domain-containing host target
FT proteins; when associated with A-24 and A-152."
FT /evidence="ECO:0000269|PubMed:32432056"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 74..84
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 100..112
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 133..145
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 154..165
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 174..178
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 185..197
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 241..248
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 251..263
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 267..278
FT /evidence="ECO:0007829|PDB:6IXK"
FT TURN 284..289
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:6IXK"
FT HELIX 305..312
FT /evidence="ECO:0007829|PDB:6IXK"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:6IXK"
SQ SEQUENCE 336 AA; 38836 MW; 77CB1A4B2316066F CRC64;
MIPPLNRYVP ALSKNELVKT VTNRDIQFTS FNGKDYPLCF LDEKTPLLFQ WFERNPARFG
KNDIPIINTE KNPYLNNIIK AATIEKERLI GIFVDGDFFP GQKDAFSKLE YDYENIKVIY
RNDIDFSMYD KKLSEIYMEN ISKQESMPEE KRDCHLLQLL KKELSDIQEG NDSLIKSYLL
DKGHGWFDFY RNMAMLKAGQ LFLEADKVGC YDLSTNSGCI YLDADMIITE KLGGIYIPDG
IAVHVERIDG RASMENGIIA VDRNNHPALL AGLEIMHTKF DADPYSDGVC NGIRKHFNYS
LNEDYNSFCD FIEFKHDNII MNTSQFTQSS WARHVQ
