Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q5ZSQ3 (DRRA_LEGPH) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 51. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Multifunctional virulence effector protein DrrA
Alternative name(s):
Defects in Rab1 recruitment protein A

Including the following 2 domains:

  1. Adenosine monophosphate-protein transferase
    Short name=AMPylator
    EC=2.7.7.n1
    Alternative name(s):
    Guanosine monophosphate-protein transferase
    Short name=GMPylator
    EC=2.7.7.n6
  2. Rab1 guanine nucleotide exchange factor
Gene names
Name:drrA
Synonyms:sidM
Ordered Locus Names:lpg2464
OrganismLegionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513) [Complete proteome] [HAMAP]
Taxonomic identifier272624 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaLegionellalesLegionellaceaeLegionella

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Catalytic activity

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

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

Subunit structure

Interacts with host RAB1A. Ref.6 Ref.7

Subcellular location

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

Domain

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

Sequence similarities

Belongs to the DrrA family.

Ontologies

Keywords
   Biological processVirulence
   Cellular componentHost cytoplasmic vesicle
Host membrane
Membrane
Secreted
   LigandATP-binding
Lipid-binding
Nucleotide-binding
   Molecular functionGuanine-nucleotide releasing factor
Nucleotidyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Gene Ontology (GO)
   Biological_processpathogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

protein adenylylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein guanylylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rab GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componenthost cell cytoplasmic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

host cell cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Rab GTPase binding

Inferred from sequence or structural similarity. Source: UniProtKB

guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-4-phosphate binding

Inferred from direct assay Ref.8. Source: UniProtKB

protein adenylyltransferase activity

Inferred from direct assay Ref.4. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.6. Source: IntAct

protein guanylyltransferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RAB1AP628207EBI-7632432,EBI-716845From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 647647Multifunctional virulence effector protein DrrA
PRO_0000417545

Regions

Region1 – 339339Adenosine monophosphate-protein transferase
Region340 – 520181Rab1 guanine nucleotide exchange factor
Region544 – 647104P4M region

Experimental info

Mutagenesis4101W → D: Almost abolishes GEF and GDF activities, but still binds Rab1. Ref.7
Mutagenesis4311G → D: Abolishes GEF and GDF activities, but still binds Rab1. Ref.7
Mutagenesis4351A → D or E: Abolishes GEF and GDF activities, but still binds Rab1. Ref.6 Ref.7
Mutagenesis451 – 4533NER → AEA: Almost abolishes GEF and GDF activities, with a more severe effect on GEF activity. Ref.5 Ref.7
Mutagenesis4801D → A: Slightly impairs GEF and GDF activities; when associated with A-483. Ref.5
Mutagenesis4831S → A: Slightly impairs GEF and GDF activities; when associated with A-480. Ref.5
Mutagenesis5411R → A: Abolishes PtdIns(4)P-binding; when associated with A-568. Ref.7
Mutagenesis5681K → A: Abolishes PtdIns(4)P-binding; when associated with A-541 or A-619. Ref.7
Mutagenesis6191T → A: Abolishes PtdIns(4)P-binding; when associated with A-568. Ref.7

Secondary structure

.................................................. 647
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q5ZSQ3 [UniParc].

Last modified November 23, 2004. Version 1.
Checksum: DCE6EC98BCC3CDCA

FASTA64773,422
        10         20         30         40         50         60 
MSIMGRIKMS VNEEQFGSLY SDERDKPLLS PTAQKKFEEY QNKLANLSKI IRENEGNEVS 

        70         80         90        100        110        120 
PWQEWENGLR QIYKEMIYDA FDALGVEMPK DMEVHFAGSL AKAQATEYSD LDAFVIVKND 

       130        140        150        160        170        180 
EDIKKVKPVF DALNNLCQRI FTASNQIYPD PIGINPSRLI GTPDDLFGML KDGMVADVEA 

       190        200        210        220        230        240 
TAMSILTSKP VLPRYELGEE LRDKIKQEPS FSNMVSAKKF YNKAIKDFTA PKEGAEVVSV 

       250        260        270        280        290        300 
KTHIMRPIDF MLMGLREEFN LYSEDGAHLS APGTIRLLRE KNLLPEEQIA RIESVYNQAM 

       310        320        330        340        350        360 
SKRFELHAEH KKEHDEMPYS DAKAMLDEVA KIRELGVQRV TRIENLENAK KLWDNANSML 

       370        380        390        400        410        420 
EKGNISGYLK AANELHKFMK EKNLKEDDLR PELSDKTISP KGYAILQSLW GAASDYSRAA 

       430        440        450        460        470        480 
ATLTESTVEP GLVSAVNKMS AFFMDCKLSP NERATPDPDF KVGKSKILVG IMQFIKDVAD 

       490        500        510        520        530        540 
PTSKIWMHNT KALMNHKIAA IQKLERSNNV NDETLESVLS SKGENLSEYL SYKYATKDEG 

       550        560        570        580        590        600 
REHRYTASTE NFKNVKEKYQ QMRGDALKTE ILADFKDKLA EATDEQSLKQ IVAELKSKDE 

       610        620        630        640 
YRILAKGQGL TTQLLGLKTS SVSSFEKMVE ETRESIKSQE RQTIKIK 

« Hide

References

« Hide 'large scale' references
[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]"The genomic sequence of the accidental pathogen Legionella pneumophila."
Chien M., Morozova I., Shi S., Sheng H., Chen J., Gomez S.M., Asamani G., Hill K., Nuara J., Feder M., Rineer J., Greenberg J.J., Steshenko V., Park S.H., Zhao B., Teplitskaya E., Edwards J.R., Pampou S. expand/collapse author list , Georghiou A., Chou I.-C., Iannuccilli W., Ulz M.E., Kim D.H., Geringer-Sameth A., Goldsberry C., Morozov P., Fischer S.G., Segal G., Qu X., Rzhetsky A., Zhang P., Cayanis E., De Jong P.J., Ju J., Kalachikov S., Shuman H.A., Russo J.J.
Science 305:1966-1968(2004) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ845395 mRNA. Translation: ABG90503.1.
AE017354 Genomic DNA. Translation: AAU28524.1.
RefSeqYP_096471.1. NC_002942.5.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ5ZSQ3. 1 interaction.
MINTMINT-7720716.
STRING272624.lpg2464.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAU28524; AAU28524; lpg2464.
GeneID3080368.
KEGGlpn:lpg2464.
PATRIC22332221. VBILegPne29832_2613.

Organism-specific databases

CMRSearch...

Phylogenomic databases

eggNOGNOG12793.
HOGENOMHOG000126893.
KOK15480.
OMAIRENEGN.
OrthoDBEOG6X6R8N.

Enzyme and pathway databases

BioCycLPNE272624:GHDI-2463-MONOMER.

Family and domain databases

InterProIPR028057. DrrA_P4M.
[Graphical view]
PfamPF14860. DrrA_P4M. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameDRRA_LEGPH
AccessionPrimary (citable) accession number: Q5ZSQ3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2012
Last sequence update: November 23, 2004
Last modified: June 11, 2014
This is version 51 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references