P0DUJ7 · SSEK3_SALTS
- ProteinProtein-arginine N-acetylglucosaminyltransferase SseK3
- GenesseK3
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids335 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Protein-arginine N-acetylglucosaminyltransferase effector that disrupts TNF signaling in infected cells, including NF-kappa-B signaling and apoptosis (PubMed:26394407, PubMed:28069818, PubMed:28522607, PubMed:29449376, PubMed:32766249).
Acts by catalyzing the transfer of a single N-acetylglucosamine (GlcNAc) to a conserved arginine residue in the death domain of host proteins such as TRADD, TNFRSF1A/TNFR1 and TNFRSF10B/TRAILR2: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions and assembly of the oligomeric TNF-alpha receptor complex, thereby disrupting TNF signaling (PubMed:28069818, PubMed:29449376, PubMed:30902834, PubMed:32766249).
Also acts on host proteins without a death domain: catalyzes arginine GlcNAcylation of host small Rab GTPase (Rab1, Rab5 and Rab11), thereby preventing GTPase activity and leading to impaired host vesicular protein transport (PubMed:32504010, PubMed:32974215).
Also mediates auto-GlcNAcylation, which is required for activity toward death domain-containing host target proteins (PubMed:32432056).
Acts by catalyzing the transfer of a single N-acetylglucosamine (GlcNAc) to a conserved arginine residue in the death domain of host proteins such as TRADD, TNFRSF1A/TNFR1 and TNFRSF10B/TRAILR2: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions and assembly of the oligomeric TNF-alpha receptor complex, thereby disrupting TNF signaling (PubMed:28069818, PubMed:29449376, PubMed:30902834, PubMed:32766249).
Also acts on host proteins without a death domain: catalyzes arginine GlcNAcylation of host small Rab GTPase (Rab1, Rab5 and Rab11), thereby preventing GTPase activity and leading to impaired host vesicular protein transport (PubMed:32504010, PubMed:32974215).
Also mediates auto-GlcNAcylation, which is required for activity toward death domain-containing host target proteins (PubMed:32432056).
Catalytic activity
- L-arginyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = H+ + N(omega)-(N-acetyl-beta-D-glucosaminyl)-L-arginyl-[protein] + UDPThis reaction proceeds in the forward direction.
Cofactor
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 51-53 | UDP-N-acetyl-alpha-D-glucosamine (UniProtKB | ChEBI) | ||||
Sequence: QWF | ||||||
Binding site | 75 | UDP-N-acetyl-alpha-D-glucosamine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 224-227 | UDP-N-acetyl-alpha-D-glucosamine (UniProtKB | ChEBI) | ||||
Sequence: YLDA | ||||||
Binding site | 228 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 258 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 325 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 327 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 327 | UDP-N-acetyl-alpha-D-glucosamine (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 332-335 | UDP-N-acetyl-alpha-D-glucosamine (UniProtKB | ChEBI) | ||||
Sequence: SSWR |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell | |
Cellular Component | host cell Golgi apparatus | |
Molecular Function | lipid binding | |
Molecular Function | manganese ion binding | |
Molecular Function | protein-arginine N-acetylglucosaminyltransferase activity | |
Molecular Function | toxin activity | |
Biological Process | symbiont-mediated perturbation of host defense-related programmed cell death |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein-arginine N-acetylglucosaminyltransferase SseK3
- EC number
- Short namesArginine GlcNAcyltransferase SseK3
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Salmonella
Accessions
- Primary accessionP0DUJ7
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Decreased apoptosis in infected macrophages, characterized by reduced CASP3, CASP8 ans CASP9 caspase activity.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 51 | Strongly reduced protein-arginine N-acetylglucosaminyltransferase activity, while retaining ability to inhibit the NF-kappa-B signaling. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 52 | Abolished protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: W → A | ||||||
Mutagenesis | 87-89 | Abolished localization to the host Golgi apparatus; when associated with A-234. | ||||
Sequence: KER → AEA | ||||||
Mutagenesis | 153 | In 4RA; abolished auto-GlcNAcylation and reduced activity toward death domain-containing host target proteins; when associated with A-184, A-305 and A-335. | ||||
Sequence: R → A | ||||||
Mutagenesis | 184 | In 4RA; abolished auto-GlcNAcylation and reduced activity toward death domain-containing host target proteins; when associated with A-153, A-305 and A-335. | ||||
Sequence: R → A | ||||||
Mutagenesis | 224 | Abolished protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 226-228 | Abolished protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: DAD → AAA | ||||||
Mutagenesis | 234 | Abolished localization to the host Golgi apparatus; when associated with 87-A-A-89. | ||||
Sequence: K → A | ||||||
Mutagenesis | 247 | Does not affect protein-arginine N-acetylglucosaminyltransferase activity, while retaining ability to inhibit the NF-kappa-B signaling. | ||||
Sequence: H → A | ||||||
Mutagenesis | 251 | Does not affect protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 258 | Abolished protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: E → A or Q | ||||||
Mutagenesis | 259 | Abolished protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 305 | In 4RA; abolished auto-GlcNAcylation and reduced activity toward death domain-containing host target proteins; when associated with A-153, A-184 and A-335. | ||||
Sequence: R → A | ||||||
Mutagenesis | 334 | Abolished protein-arginine N-acetylglucosaminyltransferase activity. | ||||
Sequence: W → A | ||||||
Mutagenesis | 335 | Does not affect protein-arginine N-acetylglucosaminyltransferase activity, but impairs the GlcNAcylation pattern of host target proteins. In 4RA; abolished auto-GlcNAcylation and reduced activity toward death domain-containing host target proteins; when associated with A-153, A-184 and A-305. | ||||
Sequence: R → A |
Miscellaneous
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000452601 | 1-335 | Protein-arginine N-acetylglucosaminyltransferase SseK3 | |||
Sequence: MFSRVRGFLSCQNYSHTATPAITLPSSGSANFAGVEYPLLPLDQHTPLLFQWFERNPSRFGENQIPIINTQQNPYLNNIINAAIIEKERTIGVLVDGNFSAGQKKALAKLEKQYENIKVIYNSDLDYSMYDKKLSDIYLENIAKIEAQPANVRDEYLLGEIKKSLNEVLKNNPEESLVSSHDKRLGHVRFDFYRNLFLLKGSNAFLEAGKHGCHHLQPGGGCIYLDADMLLTGKLGTLYLPDGIAVHVSRKGNSMSLENGIIAVNRSEHPALKKGLEIMHSKPYGDPYIDGVCGGLRHYFNCSIRHNYEEFCNFIEFKHEHIFMDTSSLTISSWR | ||||||
Glycosylation | 153 | N-beta-linked (GlcNAc) arginine; by autocatalysis | ||||
Sequence: R | ||||||
Glycosylation | 184 | N-beta-linked (GlcNAc) arginine; by autocatalysis | ||||
Sequence: R | ||||||
Glycosylation | 305 | N-beta-linked (GlcNAc) arginine; by autocatalysis | ||||
Sequence: R | ||||||
Glycosylation | 335 | N-beta-linked (GlcNAc) arginine; by autocatalysis | ||||
Sequence: R |
Post-translational modification
Auto-glycosylated: arginine GlcNAcylation is required for activity toward death domain-containing host target proteins.
Keywords
- PTM
PTM databases
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 226-228 | DXD motif | ||||
Sequence: DAD |
Domain
Adopts a GT-A fold and acts as an inverting enzyme that converts the alpha-configuration in the UDP-N-acetyl-alpha-D-glucosamine donor to the beta configuration in the N-linked (GlcNAc) arginine product.
Sequence similarities
Belongs to the glycosyltransferase NleB family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length335
- Mass (Da)37,890
- Last updated2021-06-02 v1
- Checksum2BF80A0FC929E897
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
FQ312003 EMBL· GenBank· DDBJ | CBW18025.1 EMBL· GenBank· DDBJ | Genomic DNA |