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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: -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].

Activity 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
    • toxin activity Source: UniProtKB-KW

    Keywordsi

    Molecular functionGlycosyltransferase, Toxin, Transferase
    LigandNAD

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15587
    PAER208964:G1FZ6-1174-MONOMER
    BRENDAi2.4.2.36 5087
    SABIO-RKiP11439

    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
    PRIDEiP11439

    Interactioni

    Protein-protein interaction databases

    STRINGi208964.PA1148

    Structurei

    Secondary structure

    1638
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    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
    Gene3Di3.90.1350.10, 1 hit
    InterProiView protein in InterPro
    IPR013320 ConA-like_dom_sf
    IPR015185 Exotox-A_bind
    IPR015099 Exotox-A_cataly_dom
    IPR015186 Exotox-A_middle_dom
    IPR036478 Exotox-A_middle_dom_sf
    PfamiView protein in Pfam
    PF09101 Exotox-A_bind, 1 hit
    PF09009 Exotox-A_cataly, 1 hit
    PF09102 Exotox-A_target, 1 hit
    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
    PATRICifig|208964.12.peg.1194

    Similar proteinsi

    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
    PRIDEiP11439

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAG04537; AAG04537; PA1148
    GeneIDi877850
    KEGGipae:PA1148
    PATRICifig|208964.12.peg.1194

    Organism-specific databases

    PseudoCAPiPA1148

    Phylogenomic databases

    HOGENOMiHOG000081585
    KOiK11020
    OMAiHESNEMQ

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15587
    PAER208964:G1FZ6-1174-MONOMER
    BRENDAi2.4.2.36 5087
    SABIO-RKiP11439

    Miscellaneous databases

    EvolutionaryTraceiP11439

    Family and domain databases

    CDDicd01436 Dipth_tox_like, 1 hit
    Gene3Di3.90.1350.10, 1 hit
    InterProiView protein in InterPro
    IPR013320 ConA-like_dom_sf
    IPR015185 Exotox-A_bind
    IPR015099 Exotox-A_cataly_dom
    IPR015186 Exotox-A_middle_dom
    IPR036478 Exotox-A_middle_dom_sf
    PfamiView protein in Pfam
    PF09101 Exotox-A_bind, 1 hit
    PF09009 Exotox-A_cataly, 1 hit
    PF09102 Exotox-A_target, 1 hit
    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 historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: January 11, 2001
    Last modified: September 12, 2018
    This is version 140 of the entry and version 2 of the sequence. See 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
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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