Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q5ZSQ3

- DRRA_LEGPH

UniProt

Q5ZSQ3 - DRRA_LEGPH

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 53 (01 Oct 2014)
      Sequence version 1 (23 Nov 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 binding Source: IntAct
    6. protein guanylyltransferase activity Source: UniProtKB
    7. 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. regulation of Rab GTPase activity Source: UniProtKB

    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 cytoplasmic vesicle membrane Source: UniProtKB-SubCell
    3. membrane Source: UniProtKB-KW

    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.
    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 – 22411
    Helixi240 – 2434
    Helixi245 – 25814
    Helixi271 – 28010
    Helixi286 – 30722
    Helixi320 – 3223
    Helixi336 – 36126
    Helixi365 – 38117
    Helixi386 – 3894
    Helixi390 – 3934
    Helixi400 – 41920
    Helixi428 – 44720
    Beta strandi450 – 4523
    Helixi458 – 4603
    Helixi464 – 47815
    Helixi490 – 50617
    Helixi512 – 5209
    Beta strandi526 – 5283
    Turni530 – 5334
    Helixi557 – 5593
    Helixi564 – 57916
    Helixi585 – 59612
    Helixi599 – 6057
    Helixi610 – 6156
    Helixi620 – 64526

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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

    MSIMGRIKMS VNEEQFGSLY SDERDKPLLS PTAQKKFEEY QNKLANLSKI    50
    IRENEGNEVS PWQEWENGLR QIYKEMIYDA FDALGVEMPK DMEVHFAGSL 100
    AKAQATEYSD LDAFVIVKND EDIKKVKPVF DALNNLCQRI FTASNQIYPD 150
    PIGINPSRLI GTPDDLFGML KDGMVADVEA TAMSILTSKP VLPRYELGEE 200
    LRDKIKQEPS FSNMVSAKKF YNKAIKDFTA PKEGAEVVSV KTHIMRPIDF 250
    MLMGLREEFN LYSEDGAHLS APGTIRLLRE KNLLPEEQIA RIESVYNQAM 300
    SKRFELHAEH KKEHDEMPYS DAKAMLDEVA KIRELGVQRV TRIENLENAK 350
    KLWDNANSML EKGNISGYLK AANELHKFMK EKNLKEDDLR PELSDKTISP 400
    KGYAILQSLW GAASDYSRAA ATLTESTVEP GLVSAVNKMS AFFMDCKLSP 450
    NERATPDPDF KVGKSKILVG IMQFIKDVAD PTSKIWMHNT KALMNHKIAA 500
    IQKLERSNNV NDETLESVLS SKGENLSEYL SYKYATKDEG REHRYTASTE 550
    NFKNVKEKYQ QMRGDALKTE ILADFKDKLA EATDEQSLKQ IVAELKSKDE 600
    YRILAKGQGL TTQLLGLKTS SVSSFEKMVE ETRESIKSQE RQTIKIK 647
    Length:647
    Mass (Da):73,422
    Last modified:November 23, 2004 - v1
    Checksum:iDCE6EC98BCC3CDCA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    GeneIDi3080368.
    KEGGilpn:lpg2464.
    PATRICi22332221. VBILegPne29832_2613.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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 3080368.
    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

    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: October 1, 2014
    This is version 53 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