Multifunctional virulence effector protein DrrA

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Q29ST3 (DRRA_LEGPN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 9, 2013. Version 24. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 DrrA
Short name=AMPylator DrrA
EC=2.7.7.n1
Alternative name(s):
guanosine monophosphate-protein transferase DrrA
Short name=GMPylator DrrA
EC=2.7.7.n6
Rab1 guanine nucleotide exchange factor DrrA

Gene names

Name:	drrA
Synonyms:	sidM

Organism

Legionella pneumophila

Taxonomic identifier

446 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Legionellales › Legionellaceae › Legionella

Protein attributes

Sequence length	647 AA.
Sequence status	Complete.
Protein existence	Evidence 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.2 Ref.4
Catalytic activity	ATP + [protein] = diphosphate + [protein]-AMP. Ref.4 GTP + [protein] = diphosphate + [protein]-GMP. Ref.4
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 Ref.3
Domain	The P4M (PtdIns₄P-binding) region mediates binding to PtdIns₄P and membrane attachment (Ref.3). Ref.3
Sequence similarities	Belongs to the DrrA family.

Ontologies

Keywords
Biological process	Virulence
Cellular component	Host cytoplasmic vesicle Host membrane Membrane Secreted
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Guanine-nucleotide releasing factor Nucleotidyltransferase Transferase
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from direct assay Ref.4. Source: UniProtKB regulation of Rab GTPase activity Inferred from direct assay Ref.4. Source: UniProtKB
Cellular_component	host cell cytoplasmic vesicle Inferred from direct assay Ref.1 Ref.3. Source: UniProtKB host cell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Rab GTPase binding Inferred from direct assay Ref.4. Source: UniProtKB guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.1. Source: UniProtKB phosphatidylinositol-4-phosphate binding Inferred from direct assay Ref.3. Source: UniProtKB protein adenylyltransferase activity Inferred from direct assay Ref.4. Source: UniProtKB protein guanylyltransferase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 647

647

Multifunctional virulence effector protein DrrA

PRO_0000417544

Regions

Region

1 – 218

218

Adenosine monophosphate-protein transferase activity

Region

340 – 520

181

Rab1 guanine nucletide exchange factor activity

Region

544 – 647

104

P4M region

Experimental info

Mutagenesis

110 – 112

DLD → ALA: Abolishes adenosine monophosphate-protein transferase activity. Ref.4

Secondary structure

647

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q29ST3 [UniParc].

Last modified April 4, 2006. Version 1.
Checksum: DCE6EC98BCC3CDCA
Show »

FASTA

647

73,422

        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

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References

[1]	"The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor." Murata T., Delprato A., Ingmundson A., Toomre D.K., Lambright D.G., Roy C.R. Nat. Cell Biol. 8:971-977(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A GUANINE NUCLEOTIDE EXCHANGE FACTOR, SUBCELLULAR LOCATION. Strain: 130b / Wadsworth / Serogroup 1.
[2]	"Legionella pneumophila proteins that regulate Rab1 membrane cycling." Ingmundson A., Delprato A., Lambright D.G., Roy C.R. Nature 450:365-369(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[3]	"Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila." Brombacher E., Urwyler S., Ragaz C., Weber S.S., Kami K., Overduin M., Hilbi H. J. Biol. Chem. 284:4846-4856(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PTDINS(4)P-BINDING, DOMAIN P4M, SUBCELLULAR LOCATION. Strain: JR32.
[4]	"The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b." Muller M.P., Peters H., Blumer J., Blankenfeldt W., Goody R.S., Itzen A. Science 329:946-949(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 9-218 IN COMPLEX WITH HOST RAB1B, FUNCTION AS AN ADENOSINE MONOPHOSPHATE-PROTEIN TRANSFERASE, CATALYTIC ACTIVITY, MUTAGENESIS OF 110-ASP--ASP-112.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY945933 Genomic DNA. Translation: AAY23285.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3NKU	X-ray	2.10	A/B	9-218	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-58604N.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

ProtoNet

Search...

Entry information

Entry name

DRRA_LEGPN

Accession

Primary (citable) accession number: Q29ST3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2012
Last sequence update:	April 4, 2006
Last modified:	January 9, 2013
This is version 24 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Including the following 2 domains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Family and domain databases

Entry information

Relevant documents