DRRA_LEGPN
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 25-MAY-2022, entry version 63.
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.n1 {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; Proteobacteria; Gammaproteobacteria; Legionellales;
OC 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=ATP + L-tyrosyl-[protein] = diphosphate + O-(5'-adenylyl)-L-
CC tyrosyl-[protein]; 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.n1;
CC Evidence={ECO:0000269|PubMed:20651120};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = 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.n1;
CC Evidence={ECO:0000269|PubMed:20651120};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + L-tyrosyl-[protein] = diphosphate + O-(5'-guanylyl)-L-
CC tyrosyl-[protein]; 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; P62820-1: 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_UGOV01000002.1.
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 PDBsum; 3NKU; -.
DR PDBsum; 5O74; -.
DR PDBsum; 6YX5; -.
DR AlphaFoldDB; Q29ST3; -.
DR SMR; Q29ST3; -.
DR DIP; DIP-58604N; -.
DR IntAct; Q29ST3; 2.
DR OrthoDB; 80086at2; -.
DR EvolutionaryTrace; Q29ST3; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0070733; F:protein adenylyltransferase activity; 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; 1.20.1280.280; -; 1.
DR InterPro; IPR033784; DrrA_GEF.
DR InterPro; IPR028057; DrrA_P4M.
DR InterPro; IPR038346; DrrA_PI4P-bd_sf.
DR Pfam; PF14860; DrrA_P4M; 1.
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 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..225
FT /evidence="ECO:0007829|PDB:6YX5"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:6YX5"
FT TURN 240..244
FT /evidence="ECO:0007829|PDB:6YX5"
FT HELIX 245..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 458..460
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
