SSEK1_SALTY
ID SSEK1_SALTY Reviewed; 336 AA.
AC Q9L9J3; Q7BPM9;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 92.
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:23955153, ECO:0000269|PubMed:28069818, ECO:0000269|PubMed:32366039};
DE AltName: Full=Salmonella secreted effector K1 {ECO:0000303|PubMed:15322005};
GN Name=sseK1 {ECO:0000303|PubMed:15322005, ECO:0000303|PubMed:23955153};
GN OrderedLocusNames=STM4157 {ECO:0000312|EMBL:AAL22985.1};
GN ORFNames=STMF1.17 {ECO:0000312|EMBL:AAF33527.1};
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [2]
RP SUBCELLULAR LOCATION.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=15322005; DOI=10.1128/iai.72.9.5115-5125.2004;
RA Kujat Choy S.L., Boyle E.C., Gal-Mor O., Goode D.L., Valdez Y.,
RA Vallance B.A., Finlay B.B.;
RT "SseK1 and SseK2 are novel translocated proteins of Salmonella enterica
RT serovar typhimurium.";
RL Infect. Immun. 72:5115-5125(2004).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=23955153; DOI=10.1038/nature12436;
RA Li S., Zhang L., Yao Q., Li L., Dong N., Rong J., Gao W., Ding X., Sun L.,
RA Chen X., Chen S., Shao F.;
RT "Pathogen blocks host death receptor signalling by arginine GlcNAcylation
RT of death domains.";
RL Nature 501:242-246(2013).
RN [4]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=25972862; DOI=10.3389/fmicb.2015.00396;
RA Baison-Olmo F., Galindo-Moreno M., Ramos-Morales F.;
RT "Host cell type-dependent translocation and PhoP-mediated positive
RT regulation of the effector SseK1 of Salmonella enterica.";
RL Front. Microbiol. 6:396-396(2015).
RN [5]
RP FUNCTION.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023;
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 [7]
RP ACTIVITY REGULATION.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=30619781; DOI=10.3389/fcimb.2018.00435;
RA El Qaidi S., Zhu C., McDonald P., Roy A., Maity P.K., Rane D., Perera C.,
RA Hardwidge P.R.;
RT "High-throughput screening for bacterial glycosyltransferase inhibitors.";
RL Front. Cell. Infect. Microbiol. 8:435-435(2018).
RN [8]
RP FUNCTION, AUTOGLYCOSYLATION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP 223-ASP--ASP-225.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=32366039; DOI=10.3390/ijms21093193;
RA Araujo-Garrido J.L., Baison-Olmo F., Bernal-Bayard J., Romero F.,
RA Ramos-Morales F.;
RT "Tubulin folding cofactor TBCB is a target of the salmonella effector
RT protein SseK1.";
RL Int. J. Mol. Sci. 21:0-0(2020).
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:23955153, PubMed:28522607,
CC PubMed:28069818). 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:23955153, PubMed:28069818). Also acts
CC on host proteins without a death domain: catalyzes arginine
CC GlcNAcylation of host GAPDH protein, thereby preventing GAPDH
CC interaction with TRAF2, leading to inhibit NF-kappa-B signaling
CC (PubMed:28522607). Catalyzes GlcNAcylation of host tubulin-folding
CC cofactor TBCB, thereby promoting microtubule stability
CC (PubMed:32366039). Also mediates auto-GlcNAcylation, which is required
CC for activity toward death domain-containing host target proteins
CC (PubMed:32366039). {ECO:0000269|PubMed:23955153,
CC ECO:0000269|PubMed:28069818, ECO:0000269|PubMed:28522607,
CC ECO:0000269|PubMed:32366039}.
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:23955153, ECO:0000269|PubMed:28069818,
CC ECO:0000269|PubMed:32366039};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66633;
CC Evidence={ECO:0000269|PubMed:23955153, ECO:0000269|PubMed:28069818,
CC ECO:0000269|PubMed:32366039};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:A0A0H3NK84};
CC -!- ACTIVITY REGULATION: Protein-arginine N-acetylglucosaminyltransferase
CC activity is inhibited by 100066N compound (flavone analog) and 102644N
CC compound (a substituted isoxazole). {ECO:0000269|PubMed:30619781}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15322005,
CC ECO:0000269|PubMed:25972862}. Host cytoplasm, host cytosol
CC {ECO:0000269|PubMed:15322005, ECO:0000269|PubMed:28069818}.
CC Note=Secreted via type III secretion systems 1 and 2 (SPI-1 and SPI-2
CC TTSS). {ECO:0000269|PubMed:25972862}.
CC -!- INDUCTION: Transcription is dependent on PhoP/PhoQ two-component
CC system. {ECO:0000269|PubMed:25972862}.
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:0000250|UniProtKB:A0A0H3NK84}.
CC -!- PTM: Auto-glycosylated: arginine GlcNAcylation is required for activity
CC toward death domain-containing host target proteins.
CC {ECO:0000250|UniProtKB:A0A0H3NK84}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase NleB family.
CC {ECO:0000305}.
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DR EMBL; AF170176; AAF33527.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL22985.1; -; Genomic_DNA.
DR RefSeq; NP_463026.1; NC_003197.2.
DR RefSeq; WP_010989090.1; NC_003197.2.
DR AlphaFoldDB; Q9L9J3; -.
DR SMR; Q9L9J3; -.
DR STRING; 99287.STM4157; -.
DR PaxDb; Q9L9J3; -.
DR EnsemblBacteria; AAL22985; AAL22985; STM4157.
DR GeneID; 1255683; -.
DR KEGG; stm:STM4157; -.
DR PATRIC; fig|99287.12.peg.4370; -.
DR HOGENOM; CLU_081850_0_0_6; -.
DR OMA; KGHVWFD; -.
DR PhylomeDB; Q9L9J3; -.
DR BioCyc; SENT99287:STM4157-MON; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106362; F:protein-arginine N-acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW Glycoprotein; Glycosyltransferase; Host cytoplasm; Manganese;
KW Metal-binding; Reference proteome; Secreted; Toxin; Transferase; Virulence.
FT CHAIN 1..336
FT /note="Protein-arginine N-acetylglucosaminyltransferase
FT SseK1"
FT /id="PRO_0000452596"
FT MOTIF 223..225
FT /note="DXD motif"
FT /evidence="ECO:0000305"
FT ACT_SITE 255
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 50..52
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 74
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 224..225
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 225
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 322
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 324
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 324
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT BINDING 329
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT CARBOHYD 24
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT CARBOHYD 152
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT CARBOHYD 333
FT /note="N-beta-linked (GlcNAc) arginine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3NK84"
FT MUTAGEN 223..225
FT /note="DAD->AAA: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:32366039"
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
