SSEK2_SALTS
ID SSEK2_SALTS Reviewed; 348 AA.
AC P0DUJ8;
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 SseK2 {ECO:0000305};
DE Short=Arginine GlcNAcyltransferase SseK2 {ECO:0000305};
DE EC=2.4.1.- {ECO:0000269|PubMed:30327479, ECO:0000305|PubMed:32974215};
DE AltName: Full=Salmonella secreted effector K2 {ECO:0000303|PubMed:31390974};
GN Name=sseK2 {ECO:0000303|PubMed:31390974};
GN OrderedLocusNames=SL1344_2113 {ECO:0000312|EMBL:CBW18209.1};
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 DISRUPTION PHENOTYPE.
RC STRAIN=SL1344;
RX PubMed=31390974; DOI=10.1186/s12866-019-1543-2;
RA Zhang X., He L., Zhang C., Yu C., Yang Y., Jia Y., Cheng X., Li Y.,
RA Liao C., Li J., Yu Z., Du F.;
RT "The impact of sseK2 deletion on Salmonella enterica serovar typhimurium
RT virulence in vivo and in vitro.";
RL BMC Microbiol. 19:182-182(2019).
RN [4]
RP SUBCELLULAR LOCATION.
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, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 239-ASP--ASP-241.
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 [6] {ECO:0007744|PDB:5H61, ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63}
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) IN COMPLEX WITH
RP URIDINE-5'-DIPHOSPHATE AND MANGANESE, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, DOMAIN, ACTIVE SITE, AND MUTAGENESIS OF TRP-65; PHE-203; HIS-260
RP AND 271-GLU-ASN-272.
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 catalyzes the transfer of a single N-acetylglucosamine (GlcNAc) to
CC a conserved arginine residue in the death domain of host proteins such
CC as FADD: arginine GlcNAcylation prevents homotypic/heterotypic death
CC domain interactions (PubMed:30327479). Also acts on host proteins
CC without a death domain: catalyzes arginine GlcNAcylation of host small
CC Rab1 GTPase, thereby preventing GTPase activity and leading to impaired
CC host vesicular protein transport (PubMed:32974215). In contrast to
CC Ssek1, not able to disrupt TNF signaling in infected cells (By
CC similarity). {ECO:0000250|UniProtKB:Q8ZNP4,
CC ECO:0000269|PubMed:30327479, 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:30327479, ECO:0000305|PubMed:32974215};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66633;
CC Evidence={ECO:0000269|PubMed:30327479, ECO:0000305|PubMed:32974215};
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:Q8ZNP4}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8ZNP4}. Host
CC Golgi apparatus {ECO:0000269|PubMed:32432056,
CC ECO:0000269|PubMed:32974215}. Note=Secreted via the type III secretion
CC system (TTSS). {ECO:0000250|UniProtKB:Q8ZNP4}.
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 -!- DISRUPTION PHENOTYPE: Reduced virulence. {ECO:0000269|PubMed:31390974}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase NleB family.
CC {ECO:0000305}.
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DR EMBL; FQ312003; CBW18209.1; -; Genomic_DNA.
DR RefSeq; WP_010989041.1; NZ_QASL01000003.1.
DR PDB; 5H61; X-ray; 1.86 A; A/B=1-348.
DR PDB; 5H62; X-ray; 1.66 A; A/B=1-348.
DR PDB; 5H63; X-ray; 1.92 A; A/B/C/D=1-348.
DR PDBsum; 5H61; -.
DR PDBsum; 5H62; -.
DR PDBsum; 5H63; -.
DR AlphaFoldDB; P0DUJ8; -.
DR SMR; P0DUJ8; -.
DR KEGG; sey:SL1344_2113; -.
DR OMA; LHNYNAF; -.
DR Proteomes; UP000008962; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044177; C:host cell Golgi apparatus; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Glycosyltransferase; Host Golgi apparatus; Manganese;
KW Metal-binding; Secreted; Toxin; Transferase; Virulence.
FT CHAIN 1..348
FT /note="Protein-arginine N-acetylglucosaminyltransferase
FT SseK2"
FT /id="PRO_0000452600"
FT MOTIF 239..241
FT /note="DXD motif"
FT /evidence="ECO:0000305"
FT ACT_SITE 271
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:30327479"
FT BINDING 64..66
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 88
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 237..240
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 241
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 338
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 338
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 340
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 340
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT BINDING 345..348
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000305|PubMed:30327479,
FT ECO:0007744|PDB:5H62, ECO:0007744|PDB:5H63"
FT MUTAGEN 65
FT /note="W->A: Abolished binding to UDP-N-acetyl-alpha-D-
FT glucosamine."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 203
FT /note="F->A: Reduced binding to UDP-N-acetyl-alpha-D-
FT glucosamine."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 239..241
FT /note="DAD->AAA: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:32974215"
FT MUTAGEN 260
FT /note="H->A: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity; when associated
FT with A-255 and 271-A-A-272."
FT /evidence="ECO:0000269|PubMed:30327479"
FT MUTAGEN 271..272
FT /note="EN->AA: Abolished protein-arginine N-
FT acetylglucosaminyltransferase activity; when associated
FT with A-260."
FT /evidence="ECO:0000269|PubMed:30327479"
SQ SEQUENCE 348 AA; 39566 MW; 4870E64CD4055C8E CRC64;
MARFNAAFTR IKIMFSRIRG LISCQSNTQT IAPTLSPPSS GHVSFAGIDY PLLPLNHQTP
LVFQWFERNP DRFGQNEIPI INTQKNPYLN NIINAAIIEK ERIIGIFVDG DFSKGQRKAL
GKLEQNYRNI KVIYNSDLNY SMYDKKLTTI YLENITKLEA QSASERDEVL LNGVKKSLED
VLKNNPEETL ISSHNKDKGH LWFDFYRNLF LLKGSDAFLE AGKPGCHHLQ PGGGCIYLDA
DMLLTDKLGT LYLPDGIAIH VSRKDNHVSL ENGIIAVNRS EHPALIKGLE IMHSKPYGDP
YNDWLSKGLR HYFDGSHIQD YDAFCDFIEF KHENIIMNTS SLTASSWR
