ID DRRA_LEGPN Reviewed; 647 AA. AC Q29ST3; DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot. DT 04-APR-2006, sequence version 1. DT 02-SEP-2026, entry version 76. DE RecName: Full=Multifunctional virulence effector protein DrrA; DE AltName: Full=Defects in Rab1 recruitment protein A; DE Includes: DE RecName: Full=Protein adenylyltransferase; DE Short=AMPylator; DE EC=2.7.7.108 {ECO:0000269|PubMed:20651120}; DE AltName: Full=Protein guanylyltransferase; DE Short=GMPylator; DE EC=2.7.7.n6 {ECO:0000269|PubMed:20651120}; DE Includes: DE RecName: Full=Rab1 guanine nucleotide exchange factor; GN Name=drrA; Synonyms=sidM; OS Legionella pneumophila. OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Legionellales; Legionellaceae; Legionella. OX NCBI_TaxID=446; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A GUANINE NUCLEOTIDE RP EXCHANGE FACTOR, AND SUBCELLULAR LOCATION. RC STRAIN=130b / Wadsworth / Serogroup 1; RX PubMed=16906144; DOI=10.1038/ncb1463; RA Murata T., Delprato A., Ingmundson A., Toomre D.K., Lambright D.G., RA Roy C.R.; RT "The Legionella pneumophila effector protein DrrA is a Rab1 guanine RT nucleotide-exchange factor."; RL Nat. Cell Biol. 8:971-977(2006). RN [2] RP FUNCTION. RX PubMed=17952054; DOI=10.1038/nature06336; RA Ingmundson A., Delprato A., Lambright D.G., Roy C.R.; RT "Legionella pneumophila proteins that regulate Rab1 membrane cycling."; RL Nature 450:365-369(2007). RN [3] RP PTDINS(4)P-BINDING, DOMAIN P4M, AND SUBCELLULAR LOCATION. RC STRAIN=JR32; RX PubMed=19095644; DOI=10.1074/jbc.m807505200; RA Brombacher E., Urwyler S., Ragaz C., Weber S.S., Kami K., Overduin M., RA Hilbi H.; RT "Rab1 guanine nucleotide exchange factor SidM is a major RT phosphatidylinositol 4-phosphate-binding effector protein of Legionella RT pneumophila."; RL J. Biol. Chem. 284:4846-4856(2009). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 9-218 IN COMPLEX WITH HOST RAB1B, RP FUNCTION AS A PROTEIN ADENYLYLTRANSFERASE/GUANYLYLTRANSFERASE, CATALYTIC RP ACTIVITY, AND MUTAGENESIS OF 110-ASP--ASP-112. RX PubMed=20651120; DOI=10.1126/science.1192276; RA Muller M.P., Peters H., Blumer J., Blankenfeldt W., Goody R.S., Itzen A.; RT "The Legionella effector protein DrrA AMPylates the membrane traffic RT regulator Rab1b."; RL Science 329:946-949(2010). CC -!- FUNCTION: Virulence effector that plays a key role in hijacking the CC host vesicular trafficking by recruiting the small guanosine CC triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella- CC containing vacuole (LCVs). Acts as a GDP-GTP exchange factor (GEF) for CC the small GTPase Rab1 (RAB1A, RAB1B or RAB1C), thereby converting Rab1 CC to an active GTP-bound state, leading to the incorporation of Rab1 into CC LCVs. Also shows RabGDI displacement factor (GDF) activity; however, CC this probably represents a passive activity following the GEF activity. CC Also acts as an adenylyltransferase by mediating the addition of CC adenosine 5'-monophosphate (AMP) to 'Tyr-77' of host RAB1B, thereby CC rendering RAB1B constitutively active. Also has adenylyltransferase CC activity towards Rab6 and Rab35. Also displays guanylyltransferase CC activity by mediating the addition of guanosine 5'-monophosphate (GMP) CC to host RAB1B in vitro; however such activity remains uncertain in CC vivo. Specifically binds phosphatidylinositol 4-phosphate (PtdIns(4)P) CC lipids on the cytosolic surface of the phagosomal membrane shortly CC after infection. {ECO:0000269|PubMed:16906144, CC ECO:0000269|PubMed:17952054, ECO:0000269|PubMed:20651120}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-(5'-adenylyl)-L-tyrosyl- CC [protein] + diphosphate; Xref=Rhea:RHEA:54288, Rhea:RHEA-COMP:10136, CC Rhea:RHEA-COMP:13846, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:46858, ChEBI:CHEBI:83624; EC=2.7.7.108; CC Evidence={ECO:0000269|PubMed:20651120}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = 3-O-(5'-adenylyl)-L-threonyl- CC [protein] + diphosphate; Xref=Rhea:RHEA:54292, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:13847, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:138113; EC=2.7.7.108; CC Evidence={ECO:0000269|PubMed:20651120}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + GTP = O-(5'-guanylyl)-L-tyrosyl- CC [protein] + diphosphate; Xref=Rhea:RHEA:54296, Rhea:RHEA-COMP:10136, CC Rhea:RHEA-COMP:13848, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:46858, ChEBI:CHEBI:138114; EC=2.7.7.n6; CC Evidence={ECO:0000269|PubMed:20651120}; CC -!- INTERACTION: CC Q29ST3; P62820: RAB1A; Xeno; NbExp=2; IntAct=EBI-15838677, EBI-716845; CC Q29ST3; P62820-1: RAB1A; Xeno; NbExp=3; IntAct=EBI-15838677, EBI-15666813; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19095644}. Host CC cytoplasmic vesicle membrane {ECO:0000269|PubMed:16906144}; Peripheral CC membrane protein {ECO:0000305|PubMed:16906144}. Note=Translocated into CC the host cell via the type IV secretion system (T4SS). Membrane CC association is mediated by PtdIns(4)P-binding. CC {ECO:0000269|PubMed:19095644}. CC -!- DOMAIN: The P4M (PtdIns(4)P-binding) region mediates binding to CC PtdIns(4)P and membrane attachment. {ECO:0000269|PubMed:19095644}. CC -!- SIMILARITY: Belongs to the DrrA family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY945933; AAY23285.1; -; Genomic_DNA. DR RefSeq; WP_010948166.1; NZ_CCZO01000021.1. DR PDB; 3NKU; X-ray; 2.10 A; A/B=9-218. DR PDB; 5O74; X-ray; 2.50 A; A/C/E/G/I/K=340-533. DR PDB; 6YX5; X-ray; 2.14 A; B=16-352. DR AlphaFoldDB; Q29ST3; -. DR SMR; Q29ST3; -. DR DIP; DIP-58604N; -. DR IntAct; Q29ST3; 2. DR MINT; Q29ST3; -. DR GeneID; 57036458; -. DR BRENDA; 2.7.7.108; 2943. DR EvolutionaryTrace; Q29ST3; -. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; EXP:UniProtKB. DR GO; GO:0070733; F:AMPylase activity; IDA:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB. DR GO; GO:0044600; F:protein guanylyltransferase activity; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB. DR GO; GO:0018117; P:protein adenylylation; IDA:UniProtKB. DR GO; GO:0018260; P:protein guanylylation; IDA:UniProtKB. DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB. DR CDD; cd11689; SidM_DrrA_GEF; 1. DR Gene3D; 1.10.357.170; -; 1. DR Gene3D; 1.20.120.1520; -; 1. DR Gene3D; 1.20.1280.280; -; 1. DR Gene3D; 1.20.1440.370; -; 2. DR InterPro; IPR033784; DrrA_GEF_Leg_pneum. DR InterPro; IPR028057; DrrA_P4M. DR InterPro; IPR038346; DrrA_PI4P-bd_sf. DR InterPro; IPR048717; SidM_N. DR InterPro; IPR048718; SidM_Rab1_act. DR Pfam; PF14860; DrrA_P4M; 1. DR Pfam; PF20879; SidM_N; 1. DR Pfam; PF20851; SidM_Rab1-act; 1. DR PDBsum; 3NKU; -. DR PDBsum; 5O74; -. DR PDBsum; 6YX5; -. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Guanine-nucleotide releasing factor; KW Host cytoplasmic vesicle; Host membrane; Lipid-binding; Membrane; KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; KW Secreted; Transferase; Virulence. FT CHAIN 1..647 FT /note="Multifunctional virulence effector protein DrrA" FT /id="PRO_0000417544" FT REGION 1..339 FT /note="Protein adenylyltransferase/guanylyltransferase" FT REGION 340..520 FT /note="Rab1 guanine nucleotide exchange factor" FT REGION 544..647 FT /note="P4M region" FT MUTAGEN 110..112 FT /note="DLD->ALA: Abolishes protein adenylyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:20651120" FT TURN 23..25 FT /evidence="ECO:0007829|PDB:3NKU" FT STRAND 27..29 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 31..53 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 61..84 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 87..89 FT /evidence="ECO:0007829|PDB:3NKU" FT STRAND 93..97 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:3NKU" FT STRAND 112..116 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 121..143 FT /evidence="ECO:0007829|PDB:3NKU" FT STRAND 157..161 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 163..171 FT /evidence="ECO:0007829|PDB:3NKU" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 178..186 FT /evidence="ECO:0007829|PDB:3NKU" FT STRAND 189..193 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 196..207 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 211..214 FT /evidence="ECO:0007829|PDB:3NKU" FT HELIX 217..222 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 223..227 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 229..232 FT /evidence="ECO:0007829|PDB:6YX5" FT STRAND 236..239 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 241..245 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 246..258 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 267..269 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 271..280 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 286..310 FT /evidence="ECO:0007829|PDB:6YX5" FT STRAND 316..318 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 319..348 FT /evidence="ECO:0007829|PDB:6YX5" FT HELIX 365..382 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 386..389 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 390..393 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 400..419 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 428..447 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 452..454 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 458..460 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 461..463 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 464..478 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 490..506 FT /evidence="ECO:0007829|PDB:5O74" FT HELIX 512..520 FT /evidence="ECO:0007829|PDB:5O74" FT STRAND 526..528 FT /evidence="ECO:0007829|PDB:5O74" SQ SEQUENCE 647 AA; 73422 MW; DCE6EC98BCC3CDCA CRC64; MSIMGRIKMS VNEEQFGSLY SDERDKPLLS PTAQKKFEEY QNKLANLSKI IRENEGNEVS PWQEWENGLR QIYKEMIYDA FDALGVEMPK DMEVHFAGSL AKAQATEYSD LDAFVIVKND EDIKKVKPVF DALNNLCQRI FTASNQIYPD PIGINPSRLI GTPDDLFGML KDGMVADVEA TAMSILTSKP VLPRYELGEE LRDKIKQEPS FSNMVSAKKF YNKAIKDFTA PKEGAEVVSV KTHIMRPIDF MLMGLREEFN LYSEDGAHLS APGTIRLLRE KNLLPEEQIA RIESVYNQAM SKRFELHAEH KKEHDEMPYS DAKAMLDEVA KIRELGVQRV TRIENLENAK KLWDNANSML EKGNISGYLK AANELHKFMK EKNLKEDDLR PELSDKTISP KGYAILQSLW GAASDYSRAA ATLTESTVEP GLVSAVNKMS AFFMDCKLSP NERATPDPDF KVGKSKILVG IMQFIKDVAD PTSKIWMHNT KALMNHKIAA IQKLERSNNV NDETLESVLS SKGENLSEYL SYKYATKDEG REHRYTASTE NFKNVKEKYQ QMRGDALKTE ILADFKDKLA EATDEQSLKQ IVAELKSKDE YRILAKGQGL TTQLLGLKTS SVSSFEKMVE ETRESIKSQE RQTIKIK //