| IED ID | IndEnz0002001880 |
| Enzyme Type ID | protease001880 |
| Protein Name |
Ubiquitinating/deubiquitinating enzyme SdeA Effector protein SdeA Includes: Deubiquitinase DUB EC 3.4.22.- Deneddylase Deubiquitinating enzyme ; Ubiquitin transferase EC 2.3.2.- ; Mono-ADP-ribosyltransferase mART EC 2.4.2.31 |
| Gene Name | sdeA lpg2157 |
| Organism | Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513) |
| Taxonomic Lineage | cellular organisms Bacteria Proteobacteria Gammaproteobacteria Legionellales Legionellaceae Legionella Legionella pneumophila Legionella pneumophila subsp. pneumophila Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513) |
| Enzyme Sequence | MPKYVEGVELTQEGMHAIFARMGYGDITSGSIYNGVPTIDTGALNRQGFMPVLTGVGPHRDSGHWIMLIKGPGNQYYLFDPLGKTSGEGYQNILAAQLPMGSTLSVIPNGSGLNMGLCGYWVASAGLRAHQALNQHNPPTLLNVGQTITNEMRNELDHDGYRKITGWLRAVADEFPEGDPQLDGKALRENTEKDLKIEIPTLVLPGKDTSPKEMSVKPTAPQDKSVPVWNGFSLYTDDTVKAAAQYAYDNYLGKPYTGSVESAPANFGGRMVYRQHHGLSHTLRTMAYAELIVEEARKAKLRGETLGKFKDGRTIADVTPQELKKIMIAQAFFVAGRDDEASDAKNYQKYHEQSRDAFLKYVKDNESTLIPDVFKDQEDVNFYARVIEDKSHDWESTPAHVLINQGHMVDLVRVKQPPESFLQRYFSSMQRWIGSQATEAVFGIQRQFFHATYEVVAGFDSDNKEPHLVVSGLGRYVIGEDGQPIREAPKKGQKEGDLKVFPQTYKLKENERLMRVDEFLKLPEIQNTFPGSGKHLQGGMPGMNEMDYWNRLNSLNRARCENDVDFCLKQLQTAHDKAKIEPIKQAFQSSKGKERRQPNVDEIAAARIIQQILANPDCIHDDHVLINGQKLEQQFFRDLLAKCEMAVVGSLLNDTDIGNIDTLMRHEKDTEFHSTNPEAVPVKIGEYWINDQRINNSSGNITQKKHDLIFLMQNDAWYFSRVNAIAQNRDKGSTFKEVLITTLMTPLTSKALVDTSQAKPPTRLFRGLNLSEEFTKGLIDQANAMIANTTERLFTDHSPEAFKQIKLNDLSKMSGRTNASTTTEIKLVKETWDSNVIFEMLDPDGLLHSKQVGRHGEGTESEFSVYLPEDVALVPVKVTLDGKTQKGENRYVFTFVAVKSPDFTPRHESGYAVEPFLRMQAAKLAEVKSSIEKAQRAPDLETIFNLQNEVEAVQYSHLSTGYKNFLKNTVGPVLENSLSGLMESDTDTLSKALAAFPSDTQWSAFNFEEARQAKRQMDAIKQMVGNKVVLDALTQCQDALEKQNIAGALDALKKIPSEKEMGTIRRELREQIQSARQELESLQRAVVTPVVTDEKKVRERYDALIENTSKKITELETGKLPNLDAVKKGISNLSNLKQEVTVLRNEKIRMHVGTDKVDFSDVEKLEQQIQVIDTKLADAYLLEVTKQISALDNTKPKNQTELKTKIAAFLDRTTDIEMLRNERIKKHGSSKDPLDLSDLDKLSGSLQRINQSLVSDLITTIRVSINQMEAKTFHEQEKEIQQNFELLAKLEKTLDKSKTSEKLREDIPKLNDLLVAKQKAYPQMVQMQLKSEVFVTQLREVCQANHDDLDKTRNARLRELDRLDREAGITRMVGNLIWGLTNKVGLTTDERLDIRTKQQSLARFKNELFNDKIDTDQLISNLARKRPSELQEGLGISTDNAMELHLLLTELAGKTTSPDELEERMKAIDDISTKIGREPEHLKFVMVEEDESNKKTIGF |
| Enzyme Length | 1499 |
| Uniprot Accession Number | Q5ZTK4 |
| Absorption | |
| Active Site | ACT_SITE 64; /note=For deubiquitinase activity; /evidence=ECO:0000305|PubMed:26598703; ACT_SITE 80; /note=For deubiquitinase activity; /evidence=ECO:0000305|PubMed:26598703; ACT_SITE 118; /note=Nucleophile; for deubiquitinase activity; /evidence=ECO:0000305|PubMed:26598703 |
| Activity Regulation | ACTIVITY REGULATION: Ubiquitination catalyzed by SdeA is insensitive to the cysteine alkylation agent maleimide, suggesting that a cysteine conjugation of ubiquitin does not form during the reaction. {ECO:0000269|PubMed:27049943}. |
| Binding Site | BINDING 862; /note="NAD"; /evidence="ECO:0000250|UniProtKB:P21454, ECO:0000305|PubMed:27049943" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540, ChEBI:CHEBI:142554; EC=2.4.2.31; Evidence={ECO:0000269|PubMed:27049943, ECO:0000269|PubMed:29795346, ECO:0000269|PubMed:29795347, ECO:0000269|PubMed:31330531, ECO:0000269|PubMed:31330532}; |
| DNA Binding | |
| EC Number | 3.4.22.-; 2.3.2.-; 2.4.2.31 |
| Enzyme Function | FUNCTION: Secreted effector that interferes with the host cell ubiquitin pathway and is required for intracellular bacterial replication. Catalyzes the ubiquitination of several mammalian Rab proteins (Rab33b, Rab1, Rab6a and Rab30) during L.pneumophila infection, without engaging the standard cellular enzyme cascade (E1 and E2) (PubMed:29795346). Transfers an ADP-ribose moiety from NAD to the 'Arg-42' residue of ubiquitin in a reaction that releases nicotinamide (PubMed:31330532, PubMed:31330531, PubMed:29795347). The modified ubiquitin is subsequently transferred to serine residues of the substrate protein via a phosphoribose linker that results in the release of AMP (PubMed:27912065). Cannot ubiquitinate the endosomal Rab5 or the cytoskeletal small GTPase Rac1 (PubMed:27049943). Also acts as a deubiquitinase (DUB), catalyzing the cleavage of three of the most abundant polyubiquitin chains ('Lys-11', 'Lys-48' and 'Lys-63') with a distinct preference for 'Lys-63' linkages; is thus able to efficiently remove 'Lys-63'-linked polyubiquitin chains from the phagosomal surface. Is also able to remove NEDD8 from neddylated proteins, but is unable to recognize SUMO. The DUB activity of SdeA is important for regulating the dynamics of ubiquitin association with the bacterial phagosome, but is dispensable for its role in intracellular bacterial replication (PubMed:26598703). {ECO:0000269|PubMed:26598703, ECO:0000269|PubMed:27049943, ECO:0000269|PubMed:27912065, ECO:0000269|PubMed:29795346, ECO:0000269|PubMed:29795347, ECO:0000269|PubMed:31330531, ECO:0000269|PubMed:31330532}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 766..772; /note="NAD"; /evidence="ECO:0000250|UniProtKB:P21454, ECO:0000305|PubMed:27049943" |
| Features | Active site (3); Beta strand (19); Binding site (1); Chain (1); Coiled coil (1); Erroneous initiation (1); Helix (32); Modified residue (1); Mutagenesis (9); Nucleotide binding (1); Region (3); Turn (8) |
| Keywords | 3D-structure;Coiled coil;Hydrolase;Isopeptide bond;Multifunctional enzyme;NAD;Nucleotide-binding;Protease;Reference proteome;Secreted;Thiol protease;Transferase;Ubl conjugation;Ubl conjugation pathway;Virulence |
| Interact With | |
| Induction | INDUCTION: Expression is induced during the transition from exponential to stationary phase. {ECO:0000269|PubMed:15773981}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15773981}. Host cell {ECO:0000269|PubMed:15773981}. Note=Translocated across the phagosomal membrane into host macrophages via the Dot/Icm type IV secretion system (T4SS) in an IcmS-dependent manner. Appears to localize to the cytoplasmic face of the Legionella-containing vacuole (LCV) in the early stages of infection. {ECO:0000269|PubMed:15773981}. |
| Modified Residue | MOD_RES 860; /note="5-glutamyl glutamate"; /evidence="ECO:0000269|PubMed:31330531, ECO:0000269|PubMed:31330532" |
| Post Translational Modification | PTM: Is able to ubiquitinate itself, but this modification is not required to ubiquitinate Rab33b. {ECO:0000269|PubMed:27049943}.; PTM: Glutamylated at Glu-860 by SidJ; glutamylation inhibits SdeA activity to catalyze the production of ADP-ribosylated ubiquitin. {ECO:0000269|PubMed:31330531, ECO:0000269|PubMed:31330532}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (3); X-ray crystallography (9) |
| Cross Reference PDB | 5CRA; 5CRB; 5CRC; 5YSI; 5YSJ; 5YSK; 6B7Q; 6G0C; 6WTG; 7MIR; 7PPO; 7PQE; |
| Mapped Pubmed ID | 29870726; 33583181; 34407442; 34702826; |
| Motif | |
| Gene Encoded By | |
| Mass | 169,043 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:19149 |
| Cross Reference Brenda |