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Protein

Exotoxin A

Gene

eta

Organism
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

An NAD-dependent ADP-ribosyltransferase (ADPRT). Catalyzes the transfer of the ADP ribosyl moiety of oxidized NAD (NAD+) onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. Has an LD50 of 65 ng/ml against the human lung epithelial cell line C38.1 Publication

Catalytic activityi

NAD+ + diphthamide-[translation elongation factor 2] = nicotinamide + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2].

Enzyme regulationi

Inhibited by 1,8-naphthalimide (NAP) as well as a number of poly(ADP-ribose) polymerase inhibitors and other compounds.1 Publication

Kineticsi

For ADP-ribosyltransferase activity of the catalytic fragment 399-605.

  1. KM=121 µM for NAD

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei474NAD1 Publication1
    Active sitei5781 Publication1
    Binding sitei578NAD1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi465 – 467NAD1 Publication3
    Nucleotide bindingi479 – 485NAD1 Publication7

    GO - Molecular functioni

    • NAD+-diphthamide ADP-ribosyltransferase activity Source: CACAO
    Complete GO annotation...

    Keywords - Molecular functioni

    Glycosyltransferase, Toxin, Transferase

    Keywords - Ligandi

    NAD

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15587.
    BRENDAi2.4.2.36. 5087.
    SABIO-RKP11439.

    Protein family/group databases

    TCDBi1.C.73.1.1. the pseudomonas exotoxin a (p-exoa) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Exotoxin A (EC:2.4.2.36)
    Short name:
    ETA
    Alternative name(s):
    NAD(+)--diphthamide ADP-ribosyltransferase
    PE
    Gene namesi
    Name:eta
    Ordered Locus Names:PA1148
    OrganismiPseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
    Taxonomic identifieri208964 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPseudomonadalesPseudomonadaceaePseudomonas
    Proteomesi
    • UP000002438 Componenti: Chromosome

    Organism-specific databases

    PseudoCAPiPA1148.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi82K → E: Loss of toxicity, no binding to LRP1 receptor. 1 Publication1
    Mutagenesisi481R → H: 52-fold decrease in ADPRT activity, 55-fold reduction in GH activity, 31-fold increase in dissociation constant for NAD(+). 1 Publication1
    Mutagenesisi571E → A: 833-fold decrease in ADPRT activity, 4-fold reduction in GH activity, 2-fold increase in dissociation constant for NAD(+). 1 Publication1
    Mutagenesisi576R → A: 2-fold decrease in ADPRT activity, 14-fold reduction in GH activity, 3-fold increase in dissociation constant for NAD(+). 1 Publication1
    Mutagenesisi578E → A: 666-fold decrease in ADPRT activity, 14-fold reduction in GH activity, 2-fold increase in dissociation constant for NAD(+), loss of toxicity against mouse cells. 2 Publications1

    Chemistry databases

    DrugBankiDB02701. Nicotinamide.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 251 PublicationAdd BLAST25
    ChainiPRO_000001936526 – 638Exotoxin AAdd BLAST613

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi290 ↔ 3121 Publication

    Post-translational modificationi

    The 8 cysteines participate in intrachain disulfide bonds.

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiP11439.

    Interactioni

    Protein-protein interaction databases

    STRINGi208964.PA1148.

    Structurei

    Secondary structure

    1638
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi32 – 35Combined sources4
    Beta strandi36 – 43Combined sources8
    Beta strandi49 – 54Combined sources6
    Helixi57 – 60Combined sources4
    Beta strandi63 – 74Combined sources12
    Turni76 – 79Combined sources4
    Beta strandi80 – 85Combined sources6
    Turni86 – 88Combined sources3
    Beta strandi89 – 93Combined sources5
    Beta strandi95 – 102Combined sources8
    Beta strandi106 – 108Combined sources3
    Beta strandi110 – 115Combined sources6
    Beta strandi117 – 120Combined sources4
    Beta strandi122 – 131Combined sources10
    Beta strandi136 – 145Combined sources10
    Beta strandi151 – 154Combined sources4
    Beta strandi157 – 161Combined sources5
    Helixi164 – 170Combined sources7
    Beta strandi173 – 180Combined sources8
    Beta strandi189 – 201Combined sources13
    Helixi213 – 216Combined sources4
    Helixi218 – 223Combined sources6
    Helixi225 – 227Combined sources3
    Helixi230 – 235Combined sources6
    Helixi243 – 246Combined sources4
    Beta strandi249 – 255Combined sources7
    Beta strandi270 – 273Combined sources4
    Helixi280 – 290Combined sources11
    Helixi294 – 298Combined sources5
    Helixi307 – 311Combined sources5
    Helixi313 – 325Combined sources13
    Helixi330 – 332Combined sources3
    Helixi333 – 342Combined sources10
    Turni344 – 347Combined sources4
    Helixi348 – 356Combined sources9
    Helixi358 – 376Combined sources19
    Helixi384 – 387Combined sources4
    Beta strandi392 – 396Combined sources5
    Beta strandi399 – 403Combined sources5
    Helixi408 – 410Combined sources3
    Beta strandi413 – 418Combined sources6
    Helixi422 – 424Combined sources3
    Beta strandi428 – 430Combined sources3
    Beta strandi433 – 435Combined sources3
    Beta strandi438 – 440Combined sources3
    Helixi444 – 456Combined sources13
    Beta strandi459 – 467Combined sources9
    Helixi469 – 477Combined sources9
    Helixi489 – 491Combined sources3
    Beta strandi493 – 499Combined sources7
    Helixi500 – 504Combined sources5
    Beta strandi522 – 529Combined sources8
    Helixi530 – 535Combined sources6
    Beta strandi536 – 538Combined sources3
    Beta strandi543 – 545Combined sources3
    Helixi548 – 556Combined sources9
    Beta strandi558 – 561Combined sources4
    Beta strandi566 – 572Combined sources7
    Beta strandi577 – 581Combined sources5
    Helixi583 – 587Combined sources5
    Beta strandi590 – 593Combined sources4
    Helixi609 – 611Combined sources3
    Helixi614 – 617Combined sources4
    Beta strandi626 – 628Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1AERX-ray2.30A/B425-634[»]
    1DMAX-ray2.50A/B425-638[»]
    1IKPX-ray1.45A26-638[»]
    1IKQX-ray1.62A26-638[»]
    1XK9X-ray2.10A/B424-638[»]
    1ZM2X-ray3.07B/D/F424-630[»]
    1ZM3X-ray3.07B/D/F424-630[»]
    1ZM4X-ray2.90B/D/F424-630[»]
    1ZM9X-ray2.80B/D/F424-630[»]
    2ZITX-ray3.00B/D/F425-630[»]
    3B78X-ray2.50B/D/F425-630[»]
    3B82X-ray2.35B/D/F425-630[»]
    3B8HX-ray2.50B/D/F425-630[»]
    ProteinModelPortaliP11439.
    SMRiP11439.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11439.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni26 – 277IA (required for target cell recognition)Add BLAST252
    Regioni278 – 389II (required for translocation in target cell cytoplasm)Add BLAST112
    Regioni390 – 429IBAdd BLAST40
    Regioni430 – 638III (required for ADP-ribosyl activity)Add BLAST209

    Keywords - Domaini

    Signal

    Phylogenomic databases

    HOGENOMiHOG000081585.
    KOiK11020.
    OMAiHESNEMQ.

    Family and domain databases

    CDDicd01436. Dipth_tox_like. 1 hit.
    Gene3Di2.60.120.200. 1 hit.
    3.90.1350.10. 1 hit.
    InterProiIPR013320. ConA-like_dom.
    IPR015185. Exotox-A_bind.
    IPR015099. Exotox-A_cataly_dom.
    IPR015186. Exotox-A_middle_dom.
    [Graphical view]
    PfamiPF09101. Exotox-A_bind. 1 hit.
    PF09009. Exotox-A_cataly. 1 hit.
    PF09102. Exotox-A_target. 1 hit.
    [Graphical view]
    SUPFAMiSSF49899. SSF49899. 1 hit.
    SSF56864. SSF56864. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P11439-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MHLTPHWIPL VASLGLLAGG SFASAAEEAF DLWNECAKAC VLDLKDGVRS
    60 70 80 90 100
    SRMSVDPAIA DTNGQGVLHY SMVLEGGNDA LKLAIDNALS ITSDGLTIRL
    110 120 130 140 150
    EGGVEPNKPV RYSYTRQARG SWSLNWLVPI GHEKPSNIKV FIHELNAGNQ
    160 170 180 190 200
    LSHMSPIYTI EMGDELLAKL ARDATFFVRA HESNEMQPTL AISHAGVSVV
    210 220 230 240 250
    MAQAQPRREK RWSEWASGKV LCLLDPLDGV YNYLAQQRCN LDDTWEGKIY
    260 270 280 290 300
    RVLAGNPAKH DLDIKPTVIS HRLHFPEGGS LAALTAHQAC HLPLETFTRH
    310 320 330 340 350
    RQPRGWEQLE QCGYPVQRLV ALYLAARLSW NQVDQVIRNA LASPGSGGDL
    360 370 380 390 400
    GEAIREQPEQ ARLALTLAAA ESERFVRQGT GNDEAGAASA DVVSLTCPVA
    410 420 430 440 450
    AGECAGPADS GDALLERNYP TGAEFLGDGG DISFSTRGTQ NWTVERLLQA
    460 470 480 490 500
    HRQLEERGYV FVGYHGTFLE AAQSIVFGGV RARSQDLDAI WRGFYIAGDP
    510 520 530 540 550
    ALAYGYAQDQ EPDARGRIRN GALLRVYVPR SSLPGFYRTG LTLAAPEAAG
    560 570 580 590 600
    EVERLIGHPL PLRLDAITGP EEEGGRLETI LGWPLAERTV VIPSAIPTDP
    610 620 630
    RNVGGDLDPS SIPDKEQAIS ALPDYASQPG KPPREDLK
    Length:638
    Mass (Da):69,284
    Last modified:January 11, 2001 - v2
    Checksum:i7B9AAD56A27C700A
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti4T → I in AAB59097 (PubMed:6201861).Curated1
    Sequence conflicti22F → S in AAB59097 (PubMed:6201861).Curated1
    Sequence conflicti204A → T in AAB59097 (PubMed:6201861).Curated1
    Sequence conflicti389S → N in AAB59097 (PubMed:6201861).Curated1
    Sequence conflicti432I → V in AAB59097 (PubMed:6201861).Curated1
    Sequence conflicti540G → S in AAB59097 (PubMed:6201861).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    K01397 Genomic DNA. Translation: AAB59097.1.
    AE004091 Genomic DNA. Translation: AAG04537.1.
    PIRiA30347.
    C83503.
    RefSeqiNP_249839.1. NC_002516.2.
    WP_003112478.1. NC_002516.2.

    Genome annotation databases

    EnsemblBacteriaiAAG04537; AAG04537; PA1148.
    GeneIDi877850.
    KEGGipae:PA1148.
    PATRICi19836616. VBIPseAer58763_1194.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    K01397 Genomic DNA. Translation: AAB59097.1.
    AE004091 Genomic DNA. Translation: AAG04537.1.
    PIRiA30347.
    C83503.
    RefSeqiNP_249839.1. NC_002516.2.
    WP_003112478.1. NC_002516.2.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1AERX-ray2.30A/B425-634[»]
    1DMAX-ray2.50A/B425-638[»]
    1IKPX-ray1.45A26-638[»]
    1IKQX-ray1.62A26-638[»]
    1XK9X-ray2.10A/B424-638[»]
    1ZM2X-ray3.07B/D/F424-630[»]
    1ZM3X-ray3.07B/D/F424-630[»]
    1ZM4X-ray2.90B/D/F424-630[»]
    1ZM9X-ray2.80B/D/F424-630[»]
    2ZITX-ray3.00B/D/F425-630[»]
    3B78X-ray2.50B/D/F425-630[»]
    3B82X-ray2.35B/D/F425-630[»]
    3B8HX-ray2.50B/D/F425-630[»]
    ProteinModelPortaliP11439.
    SMRiP11439.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi208964.PA1148.

    Chemistry databases

    DrugBankiDB02701. Nicotinamide.

    Protein family/group databases

    TCDBi1.C.73.1.1. the pseudomonas exotoxin a (p-exoa) family.

    Proteomic databases

    PaxDbiP11439.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAG04537; AAG04537; PA1148.
    GeneIDi877850.
    KEGGipae:PA1148.
    PATRICi19836616. VBIPseAer58763_1194.

    Organism-specific databases

    PseudoCAPiPA1148.

    Phylogenomic databases

    HOGENOMiHOG000081585.
    KOiK11020.
    OMAiHESNEMQ.

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15587.
    BRENDAi2.4.2.36. 5087.
    SABIO-RKP11439.

    Miscellaneous databases

    EvolutionaryTraceiP11439.

    Family and domain databases

    CDDicd01436. Dipth_tox_like. 1 hit.
    Gene3Di2.60.120.200. 1 hit.
    3.90.1350.10. 1 hit.
    InterProiIPR013320. ConA-like_dom.
    IPR015185. Exotox-A_bind.
    IPR015099. Exotox-A_cataly_dom.
    IPR015186. Exotox-A_middle_dom.
    [Graphical view]
    PfamiPF09101. Exotox-A_bind. 1 hit.
    PF09009. Exotox-A_cataly. 1 hit.
    PF09102. Exotox-A_target. 1 hit.
    [Graphical view]
    SUPFAMiSSF49899. SSF49899. 1 hit.
    SSF56864. SSF56864. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiTOXA_PSEAE
    AccessioniPrimary (citable) accession number: P11439
    Secondary accession number(s): Q9I4I7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: January 11, 2001
    Last modified: November 2, 2016
    This is version 133 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.