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Q5ZSQ3

- DRRA_LEGPH

UniProt

Q5ZSQ3 - DRRA_LEGPH

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Protein

Multifunctional virulence effector protein DrrA

Gene

drrA

Organism
Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Virulence effector that plays a key role in hijacking the host vesicular trafficking by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole (LCVs). Acts as a GDP-GTP exchange factor (GEF) for the small GTPase Rab1 (RAB1A, RAB1B or RAB1C), thereby converting Rab1 to an active GTP-bound state, leading to the incorporation of Rab1 into LCVs. Also shows RabGDI displacement factor (GDF) activity; however, this probably represents a passive activity following the GEF activity. Also acts as an adenylyltransferase by mediating the addition of adenosine 5'-monophosphate (AMP) to 'Tyr-77' of host RAB1B, thereby rendering RAB1B constitutively active. Also has adenylyltransferase activity towards Rab6 and Rab35. Also displays guanylyltransferase activity by mediating the addition of guanosine 5'-monophosphate (GMP) to host RAB1B in vitro; however such activity remains uncertain in vivo. Specifically binds phosphatidylinositol 4-phosphate (PtdIns4P) lipids on the cytosolic surface of the phagosomal membrane shortly after infection.6 Publications

Catalytic activityi

ATP + [protein] = diphosphate + [protein]-AMP.
GTP + [protein] = diphosphate + [protein]-GMP.

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. guanyl-nucleotide exchange factor activity Source: UniProtKB
  3. phosphatidylinositol-4-phosphate binding Source: UniProtKB
  4. protein adenylyltransferase activity Source: UniProtKB
  5. protein guanylyltransferase activity Source: UniProtKB
  6. Rab GTPase binding Source: UniProtKB

GO - Biological processi

  1. pathogenesis Source: UniProtKB
  2. positive regulation of GTPase activity Source: GOC
  3. protein adenylylation Source: UniProtKB
  4. protein guanylylation Source: UniProtKB
  5. protein targeting to membrane Source: UniProtKB
  6. regulation of Rab GTPase activity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor, Nucleotidyltransferase, Transferase

Keywords - Biological processi

Virulence

Keywords - Ligandi

ATP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciLPNE272624:GHDI-2463-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Multifunctional virulence effector protein DrrA
Alternative name(s):
Defects in Rab1 recruitment protein A
Including the following 2 domains:
Adenosine monophosphate-protein transferase (EC:2.7.7.n1)
Short name:
AMPylator
Alternative name(s):
Guanosine monophosphate-protein transferase (EC:2.7.7.n6)
Short name:
GMPylator
Rab1 guanine nucleotide exchange factor
Gene namesi
Name:drrA
Synonyms:sidM
Ordered Locus Names:lpg2464
OrganismiLegionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
Taxonomic identifieri272624 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaLegionellalesLegionellaceaeLegionella
ProteomesiUP000000609: Chromosome

Subcellular locationi

Secreted 1 Publication. Host cytoplasmic vesicle membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Translocated into the host cell via the type IV secretion system (T4SS). Membrane association is mediated by PtdIns4P-binding.

GO - Cellular componenti

  1. host cell cytoplasmic vesicle Source: UniProtKB
  2. host cell membrane Source: UniProtKB-KW
  3. membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasmic vesicle, Host membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi410 – 4101W → D: Almost abolishes GEF and GDF activities, but still binds Rab1. 1 Publication
Mutagenesisi431 – 4311G → D: Abolishes GEF and GDF activities, but still binds Rab1. 1 Publication
Mutagenesisi435 – 4351A → D or E: Abolishes GEF and GDF activities, but still binds Rab1. 2 Publications
Mutagenesisi451 – 4533NER → AEA: Almost abolishes GEF and GDF activities, with a more severe effect on GEF activity. 2 Publications
Mutagenesisi480 – 4801D → A: Slightly impairs GEF and GDF activities; when associated with A-483. 1 Publication
Mutagenesisi483 – 4831S → A: Slightly impairs GEF and GDF activities; when associated with A-480. 1 Publication
Mutagenesisi541 – 5411R → A: Abolishes PtdIns(4)P-binding; when associated with A-568. 1 Publication
Mutagenesisi568 – 5681K → A: Abolishes PtdIns(4)P-binding; when associated with A-541 or A-619. 1 Publication
Mutagenesisi619 – 6191T → A: Abolishes PtdIns(4)P-binding; when associated with A-568. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 647647Multifunctional virulence effector protein DrrAPRO_0000417545Add
BLAST

Interactioni

Subunit structurei

Interacts with host RAB1A.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RAB1AP628207EBI-7632432,EBI-716845From a different organism.

Protein-protein interaction databases

IntActiQ5ZSQ3. 1 interaction.
MINTiMINT-7720716.
STRINGi272624.lpg2464.

Structurei

Secondary structure

1
647
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi214 – 22411Combined sources
Helixi240 – 2434Combined sources
Helixi245 – 25814Combined sources
Helixi271 – 28010Combined sources
Helixi286 – 30722Combined sources
Helixi320 – 3223Combined sources
Helixi336 – 36126Combined sources
Helixi365 – 38117Combined sources
Helixi386 – 3894Combined sources
Helixi390 – 3934Combined sources
Helixi400 – 41920Combined sources
Helixi428 – 44720Combined sources
Beta strandi450 – 4523Combined sources
Helixi458 – 4603Combined sources
Helixi464 – 47815Combined sources
Helixi490 – 50617Combined sources
Helixi512 – 5209Combined sources
Beta strandi526 – 5283Combined sources
Turni530 – 5334Combined sources
Helixi557 – 5593Combined sources
Helixi564 – 57916Combined sources
Helixi585 – 59612Combined sources
Helixi599 – 6057Combined sources
Helixi610 – 6156Combined sources
Helixi620 – 64526Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WWXX-ray1.50B317-533[»]
3JZ9X-ray1.80A340-533[»]
3JZAX-ray1.80B340-533[»]
3L0IX-ray2.85A/C193-550[»]
3L0MX-ray3.45A/B317-647[»]
3N6OX-ray2.50A/B340-647[»]
4MXPX-ray1.83A330-647[»]
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 339339Adenosine monophosphate-protein transferaseAdd
BLAST
Regioni340 – 520181Rab1 guanine nucleotide exchange factorAdd
BLAST
Regioni544 – 647104P4M regionAdd
BLAST

Domaini

The P4M (PtdIns4P-binding) region mediates binding to PtdIns4P and membrane attachment.By similarity

Sequence similaritiesi

Belongs to the DrrA family.Curated

Phylogenomic databases

eggNOGiNOG12793.
HOGENOMiHOG000126893.
KOiK15480.
OMAiIRENEGN.
OrthoDBiEOG6X6R8N.

Family and domain databases

InterProiIPR028057. DrrA_P4M.
[Graphical view]
PfamiPF14860. DrrA_P4M. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5ZSQ3-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSIMGRIKMS VNEEQFGSLY SDERDKPLLS PTAQKKFEEY QNKLANLSKI
60 70 80 90 100
IRENEGNEVS PWQEWENGLR QIYKEMIYDA FDALGVEMPK DMEVHFAGSL
110 120 130 140 150
AKAQATEYSD LDAFVIVKND EDIKKVKPVF DALNNLCQRI FTASNQIYPD
160 170 180 190 200
PIGINPSRLI GTPDDLFGML KDGMVADVEA TAMSILTSKP VLPRYELGEE
210 220 230 240 250
LRDKIKQEPS FSNMVSAKKF YNKAIKDFTA PKEGAEVVSV KTHIMRPIDF
260 270 280 290 300
MLMGLREEFN LYSEDGAHLS APGTIRLLRE KNLLPEEQIA RIESVYNQAM
310 320 330 340 350
SKRFELHAEH KKEHDEMPYS DAKAMLDEVA KIRELGVQRV TRIENLENAK
360 370 380 390 400
KLWDNANSML EKGNISGYLK AANELHKFMK EKNLKEDDLR PELSDKTISP
410 420 430 440 450
KGYAILQSLW GAASDYSRAA ATLTESTVEP GLVSAVNKMS AFFMDCKLSP
460 470 480 490 500
NERATPDPDF KVGKSKILVG IMQFIKDVAD PTSKIWMHNT KALMNHKIAA
510 520 530 540 550
IQKLERSNNV NDETLESVLS SKGENLSEYL SYKYATKDEG REHRYTASTE
560 570 580 590 600
NFKNVKEKYQ QMRGDALKTE ILADFKDKLA EATDEQSLKQ IVAELKSKDE
610 620 630 640
YRILAKGQGL TTQLLGLKTS SVSSFEKMVE ETRESIKSQE RQTIKIK
Length:647
Mass (Da):73,422
Last modified:November 23, 2004 - v1
Checksum:iDCE6EC98BCC3CDCA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ845395 mRNA. Translation: ABG90503.1.
AE017354 Genomic DNA. Translation: AAU28524.1.
RefSeqiWP_010948166.1. NC_002942.5.
YP_096471.1. NC_002942.5.

Genome annotation databases

EnsemblBacteriaiAAU28524; AAU28524; lpg2464.
GeneIDi19834029.
KEGGilpn:lpg2464.
PATRICi22332221. VBILegPne29832_2613.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ845395 mRNA. Translation: ABG90503.1 .
AE017354 Genomic DNA. Translation: AAU28524.1 .
RefSeqi WP_010948166.1. NC_002942.5.
YP_096471.1. NC_002942.5.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2WWX X-ray 1.50 B 317-533 [» ]
3JZ9 X-ray 1.80 A 340-533 [» ]
3JZA X-ray 1.80 B 340-533 [» ]
3L0I X-ray 2.85 A/C 193-550 [» ]
3L0M X-ray 3.45 A/B 317-647 [» ]
3N6O X-ray 2.50 A/B 340-647 [» ]
4MXP X-ray 1.83 A 330-647 [» ]
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q5ZSQ3. 1 interaction.
MINTi MINT-7720716.
STRINGi 272624.lpg2464.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblBacteriai AAU28524 ; AAU28524 ; lpg2464 .
GeneIDi 19834029.
KEGGi lpn:lpg2464.
PATRICi 22332221. VBILegPne29832_2613.

Phylogenomic databases

eggNOGi NOG12793.
HOGENOMi HOG000126893.
KOi K15480.
OMAi IRENEGN.
OrthoDBi EOG6X6R8N.

Enzyme and pathway databases

BioCyci LPNE272624:GHDI-2463-MONOMER.

Family and domain databases

InterProi IPR028057. DrrA_P4M.
[Graphical view ]
Pfami PF14860. DrrA_P4M. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila."
    Machner M.P., Isberg R.R.
    Dev. Cell 11:47-56(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS A GUANINE NUCLEOTIDE EXCHANGE FACTOR, SUBCELLULAR LOCATION.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  3. "A bifunctional bacterial protein links GDI displacement to Rab1 activation."
    Machner M.P., Isberg R.R.
    Science 318:974-977(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  4. "Modulation of Rab GTPase function by a protein phosphocholine transferase."
    Mukherjee S., Liu X., Arasaki K., McDonough J., Galan J.E., Roy C.R.
    Nature 477:103-106(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  5. "RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity."
    Schoebel S., Oesterlin L.K., Blankenfeldt W., Goody R.S., Itzen A.
    Mol. Cell 36:1060-1072(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 340-533, FUNCTION, MUTAGENESIS OF 451-ASN--ARG-453; ASP-480 AND SER-483.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  6. "Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA."
    Suh H.Y., Lee D.W., Lee K.H., Ku B., Choi S.J., Woo J.S., Kim Y.G., Oh B.H.
    EMBO J. 29:496-504(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 317-533, FUNCTION, INTERACTION WITH HOST RAB1A, MUTAGENESIS OF ALA-435.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  7. "Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA."
    Zhu Y., Hu L., Zhou Y., Yao Q., Liu L., Shao F.
    Proc. Natl. Acad. Sci. U.S.A. 107:4699-4704(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 193-550, FUNCTION, INTERACTION WITH HOST RAB1A, MUTAGENESIS OF TRP-410; GLY-431; ALA-435; 451-ASN--ARG-453; ARG-541; LYS-568 AND THR-619.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.
  8. "High-affinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA."
    Schoebel S., Blankenfeldt W., Goody R.S., Itzen A.
    EMBO Rep. 11:598-604(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 340-647, PTDINS(4)P-BINDING.
    Strain: Philadelphia 1 / ATCC 33152 / DSM 7513.

Entry informationi

Entry nameiDRRA_LEGPH
AccessioniPrimary (citable) accession number: Q5ZSQ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2012
Last sequence update: November 23, 2004
Last modified: November 26, 2014
This is version 55 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3