UniProtKB - P11439 (TOXA_PSEAE)
Protein
Exotoxin A
Gene
eta
Organism
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
Status
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
- diphthamide-[translation elongation factor 2] + NAD+ = H+ + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2] + nicotinamideEC:2.4.2.36
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.
- KM=121 µM for NAD
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 474 | NAD1 Publication | 1 | |
Active sitei | 578 | 1 Publication | 1 | |
Binding sitei | 578 | NAD1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 465 – 467 | NAD1 Publication | 3 | |
Nucleotide bindingi | 479 – 485 | NAD1 Publication | 7 |
GO - Molecular functioni
- NAD+-diphthamide ADP-ribosyltransferase activity Source: CACAO
- toxin activity Source: UniProtKB-KW
GO - Biological processi
- pathogenesis Source: UniProtKB-KW
Keywordsi
Molecular function | Glycosyltransferase, Toxin, Transferase |
Biological process | Virulence |
Ligand | NAD |
Enzyme and pathway databases
BioCyci | MetaCyc:MONOMER-15587 PAER208964:G1FZ6-1174-MONOMER |
BRENDAi | 2.4.2.36, 5087 |
SABIO-RKi | P11439 |
Protein family/group databases
TCDBi | 1.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 |
Organismi | Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) |
Taxonomic identifieri | 208964 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Pseudomonadales › Pseudomonadaceae › Pseudomonas › |
Proteomesi |
|
Organism-specific databases
PseudoCAPi | PA1148 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 82 | K → E: Loss of toxicity, no binding to LRP1 receptor. 1 Publication | 1 | |
Mutagenesisi | 481 | R → H: 52-fold decrease in ADPRT activity, 55-fold reduction in GH activity, 31-fold increase in dissociation constant for NAD(+). 1 Publication | 1 | |
Mutagenesisi | 571 | E → A: 833-fold decrease in ADPRT activity, 4-fold reduction in GH activity, 2-fold increase in dissociation constant for NAD(+). 1 Publication | 1 | |
Mutagenesisi | 576 | R → A: 2-fold decrease in ADPRT activity, 14-fold reduction in GH activity, 3-fold increase in dissociation constant for NAD(+). 1 Publication | 1 | |
Mutagenesisi | 578 | E → 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 Publications | 1 |
Chemistry databases
DrugBanki | DB02701, Nicotinamide DB08348, N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 25 | 1 PublicationAdd BLAST | 25 | |
ChainiPRO_0000019365 | 26 – 638 | Exotoxin AAdd BLAST | 613 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 290 ↔ 312 | 1 Publication |
Post-translational modificationi
The 8 cysteines participate in intrachain disulfide bonds.
Keywords - PTMi
Disulfide bondProteomic databases
PaxDbi | P11439 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P11439 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P11439 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 26 – 277 | IA (required for target cell recognition)Add BLAST | 252 | |
Regioni | 278 – 389 | II (required for translocation in target cell cytoplasm)Add BLAST | 112 | |
Regioni | 390 – 429 | IBAdd BLAST | 40 | |
Regioni | 430 – 638 | III (required for ADP-ribosyl activity)Add BLAST | 209 |
Keywords - Domaini
SignalPhylogenomic databases
HOGENOMi | CLU_426954_0_0_6 |
OMAi | HESNEMQ |
Family and domain databases
CDDi | cd01436, Dipth_tox_like, 1 hit |
Gene3Di | 3.90.1350.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF09101, Exotox-A_bind, 1 hit PF09009, Exotox-A_cataly, 1 hit PF09102, Exotox-A_target, 1 hit |
SUPFAMi | SSF49899, SSF49899, 1 hit SSF56864, SSF56864, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P11439-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 4 | T → I in AAB59097 (PubMed:6201861).Curated | 1 | |
Sequence conflicti | 22 | F → S in AAB59097 (PubMed:6201861).Curated | 1 | |
Sequence conflicti | 204 | A → T in AAB59097 (PubMed:6201861).Curated | 1 | |
Sequence conflicti | 389 | S → N in AAB59097 (PubMed:6201861).Curated | 1 | |
Sequence conflicti | 432 | I → V in AAB59097 (PubMed:6201861).Curated | 1 | |
Sequence conflicti | 540 | G → S in AAB59097 (PubMed:6201861).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | K01397 Genomic DNA Translation: AAB59097.1 AE004091 Genomic DNA Translation: AAG04537.1 |
PIRi | A30347 C83503 |
RefSeqi | NP_249839.1, NC_002516.2 WP_003112478.1, NZ_QZGE01000006.1 |
Genome annotation databases
EnsemblBacteriai | AAG04537; AAG04537; PA1148 |
GeneIDi | 877850 |
KEGGi | pae:PA1148 |
PATRICi | fig|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 |
PIRi | A30347 C83503 |
RefSeqi | NP_249839.1, NC_002516.2 WP_003112478.1, NZ_QZGE01000006.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1AER | X-ray | 2.30 | A/B | 425-634 | [»] | |
1DMA | X-ray | 2.50 | A/B | 425-638 | [»] | |
1IKP | X-ray | 1.45 | A | 26-638 | [»] | |
1IKQ | X-ray | 1.62 | A | 26-638 | [»] | |
1XK9 | X-ray | 2.10 | A/B | 424-638 | [»] | |
1ZM2 | X-ray | 3.07 | B/D/F | 424-630 | [»] | |
1ZM3 | X-ray | 3.07 | B/D/F | 424-630 | [»] | |
1ZM4 | X-ray | 2.90 | B/D/F | 424-630 | [»] | |
1ZM9 | X-ray | 2.80 | B/D/F | 424-630 | [»] | |
2ZIT | X-ray | 3.00 | B/D/F | 425-630 | [»] | |
3B78 | X-ray | 2.50 | B/D/F | 425-630 | [»] | |
3B82 | X-ray | 2.35 | B/D/F | 425-630 | [»] | |
3B8H | X-ray | 2.50 | B/D/F | 425-630 | [»] | |
SMRi | P11439 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Chemistry databases
DrugBanki | DB02701, Nicotinamide DB08348, N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE |
Protein family/group databases
TCDBi | 1.C.73.1.1, the pseudomonas exotoxin a (p-exoa) family |
Proteomic databases
PaxDbi | P11439 |
Protocols and materials databases
ABCDi | P11439, 1 sequenced antibody |
Genome annotation databases
EnsemblBacteriai | AAG04537; AAG04537; PA1148 |
GeneIDi | 877850 |
KEGGi | pae:PA1148 |
PATRICi | fig|208964.12.peg.1194 |
Organism-specific databases
PseudoCAPi | PA1148 |
Phylogenomic databases
HOGENOMi | CLU_426954_0_0_6 |
OMAi | HESNEMQ |
Enzyme and pathway databases
BioCyci | MetaCyc:MONOMER-15587 PAER208964:G1FZ6-1174-MONOMER |
BRENDAi | 2.4.2.36, 5087 |
SABIO-RKi | P11439 |
Miscellaneous databases
EvolutionaryTracei | P11439 |
Family and domain databases
CDDi | cd01436, Dipth_tox_like, 1 hit |
Gene3Di | 3.90.1350.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF09101, Exotox-A_bind, 1 hit PF09009, Exotox-A_cataly, 1 hit PF09102, Exotox-A_target, 1 hit |
SUPFAMi | SSF49899, SSF49899, 1 hit SSF56864, SSF56864, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TOXA_PSEAE | |
Accessioni | P11439Primary (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: | December 2, 2020 | |
This is version 151 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references