DRRA_LEGPH
ID DRRA_LEGPH Reviewed; 647 AA.
AC Q5ZSQ3;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 91.
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;
DE AltName: Full=Protein guanylyltransferase;
DE Short=GMPylator;
DE EC=2.7.7.n6;
DE Includes:
DE RecName: Full=Rab1 guanine nucleotide exchange factor;
GN Name=drrA; Synonyms=sidM; OrderedLocusNames=lpg2464;
OS Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC
OS 33152 / DSM 7513).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales;
OC Legionellaceae; Legionella.
OX NCBI_TaxID=272624;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS A GUANINE NUCLEOTIDE EXCHANGE
RP FACTOR, AND SUBCELLULAR LOCATION.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=16824952; DOI=10.1016/j.devcel.2006.05.013;
RA Machner M.P., Isberg R.R.;
RT "Targeting of host Rab GTPase function by the intravacuolar pathogen
RT Legionella pneumophila.";
RL Dev. Cell 11:47-56(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=15448271; DOI=10.1126/science.1099776;
RA Chien M., Morozova I., Shi S., Sheng H., Chen J., Gomez S.M., Asamani G.,
RA Hill K., Nuara J., Feder M., Rineer J., Greenberg J.J., Steshenko V.,
RA Park S.H., Zhao B., Teplitskaya E., Edwards J.R., Pampou S., Georghiou A.,
RA Chou I.-C., Iannuccilli W., Ulz M.E., Kim D.H., Geringer-Sameth A.,
RA Goldsberry C., Morozov P., Fischer S.G., Segal G., Qu X., Rzhetsky A.,
RA Zhang P., Cayanis E., De Jong P.J., Ju J., Kalachikov S., Shuman H.A.,
RA Russo J.J.;
RT "The genomic sequence of the accidental pathogen Legionella pneumophila.";
RL Science 305:1966-1968(2004).
RN [3]
RP FUNCTION.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=17947549; DOI=10.1126/science.1149121;
RA Machner M.P., Isberg R.R.;
RT "A bifunctional bacterial protein links GDI displacement to Rab1
RT activation.";
RL Science 318:974-977(2007).
RN [4]
RP FUNCTION.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=21822290; DOI=10.1038/nature10335;
RA Mukherjee S., Liu X., Arasaki K., McDonough J., Galan J.E., Roy C.R.;
RT "Modulation of Rab GTPase function by a protein phosphocholine
RT transferase.";
RL Nature 477:103-106(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 340-533, FUNCTION, AND
RP MUTAGENESIS OF 451-ASN--ARG-453; ASP-480 AND SER-483.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=20064470; DOI=10.1016/j.molcel.2009.11.014;
RA Schoebel S., Oesterlin L.K., Blankenfeldt W., Goody R.S., Itzen A.;
RT "RabGDI displacement by DrrA from Legionella is a consequence of its
RT guanine nucleotide exchange activity.";
RL Mol. Cell 36:1060-1072(2009).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 317-533, FUNCTION, INTERACTION
RP WITH HOST RAB1A, AND MUTAGENESIS OF ALA-435.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=19942850; DOI=10.1038/emboj.2009.347;
RA Suh H.Y., Lee D.W., Lee K.H., Ku B., Choi S.J., Woo J.S., Kim Y.G.,
RA Oh B.H.;
RT "Structural insights into the dual nucleotide exchange and GDI displacement
RT activity of SidM/DrrA.";
RL EMBO J. 29:496-504(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 193-550, FUNCTION, INTERACTION
RP WITH HOST RAB1A, AND MUTAGENESIS OF TRP-410; GLY-431; ALA-435;
RP 451-ASN--ARG-453; ARG-541; LYS-568 AND THR-619.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=20176951; DOI=10.1073/pnas.0914231107;
RA Zhu Y., Hu L., Zhou Y., Yao Q., Liu L., Shao F.;
RT "Structural mechanism of host Rab1 activation by the bifunctional
RT Legionella type IV effector SidM/DrrA.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4699-4704(2010).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 340-647, AND PTDINS(4)P-BINDING.
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=20616805; DOI=10.1038/embor.2010.97;
RA Schoebel S., Blankenfeldt W., Goody R.S., Itzen A.;
RT "High-affinity binding of phosphatidylinositol 4-phosphate by Legionella
RT pneumophila DrrA.";
RL EMBO Rep. 11:598-604(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:16824952,
CC ECO:0000269|PubMed:17947549, ECO:0000269|PubMed:19942850,
CC ECO:0000269|PubMed:20064470, ECO:0000269|PubMed:20176951,
CC ECO:0000269|PubMed:21822290}.
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 -!- 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 -!- 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 -!- SUBUNIT: Interacts with host RAB1A. {ECO:0000269|PubMed:19942850,
CC ECO:0000269|PubMed:20176951}.
CC -!- INTERACTION:
CC Q5ZSQ3; P62820: RAB1A; Xeno; NbExp=7; IntAct=EBI-7632432, EBI-716845;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16824952}. Host
CC cytoplasmic vesicle membrane {ECO:0000269|PubMed:16824952}; Peripheral
CC membrane protein {ECO:0000269|PubMed:16824952}. 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 -!- DOMAIN: The P4M (PtdIns(4)P-binding) region mediates binding to
CC PtdIns(4)P and membrane attachment. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DrrA family. {ECO:0000305}.
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DR EMBL; DQ845395; ABG90503.1; -; mRNA.
DR EMBL; AE017354; AAU28524.1; -; Genomic_DNA.
DR RefSeq; WP_010948166.1; NC_002942.5.
DR RefSeq; YP_096471.1; NC_002942.5.
DR PDB; 2WWX; X-ray; 1.50 A; B=317-533.
DR PDB; 3JZ9; X-ray; 1.80 A; A=340-533.
DR PDB; 3JZA; X-ray; 1.80 A; B=340-533.
DR PDB; 3L0I; X-ray; 2.85 A; A/C=193-550.
DR PDB; 3L0M; X-ray; 3.45 A; A/B=317-647.
DR PDB; 3N6O; X-ray; 2.50 A; A/B=340-647.
DR PDB; 4MXP; X-ray; 1.83 A; A=330-647.
DR PDBsum; 2WWX; -.
DR PDBsum; 3JZ9; -.
DR PDBsum; 3JZA; -.
DR PDBsum; 3L0I; -.
DR PDBsum; 3L0M; -.
DR PDBsum; 3N6O; -.
DR PDBsum; 4MXP; -.
DR AlphaFoldDB; Q5ZSQ3; -.
DR SMR; Q5ZSQ3; -.
DR IntAct; Q5ZSQ3; 1.
DR MINT; Q5ZSQ3; -.
DR STRING; 272624.lpg2464; -.
DR PaxDb; Q5ZSQ3; -.
DR PRIDE; Q5ZSQ3; -.
DR EnsemblBacteria; AAU28524; AAU28524; lpg2464.
DR KEGG; lpn:lpg2464; -.
DR PATRIC; fig|272624.6.peg.2613; -.
DR eggNOG; ENOG5031EKF; Bacteria.
DR HOGENOM; CLU_428136_0_0_6; -.
DR OMA; THIMRPI; -.
DR SABIO-RK; Q5ZSQ3; -.
DR EvolutionaryTrace; Q5ZSQ3; -.
DR Proteomes; UP000000609; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; ISS: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; ISS: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; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0018117; P:protein adenylylation; ISS:UniProtKB.
DR GO; GO:0018260; P:protein guanylylation; ISS:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; IMP:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS: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 Reference proteome; Secreted; Transferase; Virulence.
FT CHAIN 1..647
FT /note="Multifunctional virulence effector protein DrrA"
FT /id="PRO_0000417545"
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 410
FT /note="W->D: Almost abolishes GEF and GDF activities, but
FT still binds Rab1."
FT /evidence="ECO:0000269|PubMed:20176951"
FT MUTAGEN 431
FT /note="G->D: Abolishes GEF and GDF activities, but still
FT binds Rab1."
FT /evidence="ECO:0000269|PubMed:20176951"
FT MUTAGEN 435
FT /note="A->D,E: Abolishes GEF and GDF activities, but still
FT binds Rab1."
FT /evidence="ECO:0000269|PubMed:19942850,
FT ECO:0000269|PubMed:20176951"
FT MUTAGEN 451..453
FT /note="NER->AEA: Almost abolishes GEF and GDF activities,
FT with a more severe effect on GEF activity."
FT /evidence="ECO:0000269|PubMed:20064470,
FT ECO:0000269|PubMed:20176951"
FT MUTAGEN 480
FT /note="D->A: Slightly impairs GEF and GDF activities; when
FT associated with A-483."
FT /evidence="ECO:0000269|PubMed:20064470"
FT MUTAGEN 483
FT /note="S->A: Slightly impairs GEF and GDF activities; when
FT associated with A-480."
FT /evidence="ECO:0000269|PubMed:20064470"
FT MUTAGEN 541
FT /note="R->A: Abolishes PtdIns(4)P-binding; when associated
FT with A-568."
FT /evidence="ECO:0000269|PubMed:20176951"
FT MUTAGEN 568
FT /note="K->A: Abolishes PtdIns(4)P-binding; when associated
FT with A-541 or A-619."
FT /evidence="ECO:0000269|PubMed:20176951"
FT MUTAGEN 619
FT /note="T->A: Abolishes PtdIns(4)P-binding; when associated
FT with A-568."
FT /evidence="ECO:0000269|PubMed:20176951"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 240..243
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 245..258
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 286..307
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 336..361
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 365..381
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 386..389
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 400..419
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 428..447
FT /evidence="ECO:0007829|PDB:2WWX"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:3JZ9"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:3JZA"
FT HELIX 464..478
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 490..506
FT /evidence="ECO:0007829|PDB:2WWX"
FT HELIX 512..520
FT /evidence="ECO:0007829|PDB:2WWX"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:3JZ9"
FT TURN 530..533
FT /evidence="ECO:0007829|PDB:3L0I"
FT HELIX 557..559
FT /evidence="ECO:0007829|PDB:4MXP"
FT HELIX 564..579
FT /evidence="ECO:0007829|PDB:4MXP"
FT HELIX 585..596
FT /evidence="ECO:0007829|PDB:4MXP"
FT HELIX 599..605
FT /evidence="ECO:0007829|PDB:4MXP"
FT HELIX 610..615
FT /evidence="ECO:0007829|PDB:4MXP"
FT HELIX 620..645
FT /evidence="ECO:0007829|PDB:4MXP"
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
