P13423 (PAG_BACAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protective antigen
Short name=PA

Alternative name(s):
Anthrax toxins translocating protein
PA-83
Short name=PA83

Cleaved into the following 2 chains:

1. Protective antigen PA-20
   Short name=PA20
2. Protective antigen PA-63
   Short name=PA63

Gene names

Name:	pagA
Synonyms:	pag
Ordered Locus Names:	pXO1-110, BXA0164, GBAA_pXO1_0164

Encoded on

Plasmid pXO1

Organism

Bacillus anthracis [Reference proteome] [HAMAP]

Taxonomic identifier

1392 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Bacillales › Bacillaceae › Bacillus › Bacillus cereus group

Protein attributes

Sequence length	764 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax.
Subunit structure	Anthrax toxins are composed of three distinct proteins, a protective antigen (PA), a lethal factor (LF) and an edema factor (EF). None of these is toxic by itself. PA+LF forms the lethal toxin (LeTx); PA+EF forms the edema toxin (EdTx). PA-63 forms heptamers and this oligomerization is required for LF or EF binding. This complex is endocytosed by the host. Once activated, at low pH, the heptamer undergoes conformational changes and converts from prepore to pore inserted in the membrane, forming cation-selective channels and triggering the release of LF and EF in the host cytoplasm.
Subcellular location	Secreted › extracellular space. Note: Secreted through the Sec-dependent secretion pathway. Therefore, PA is translocated across the membrane in an unfolded state and then it is folded into its native configuration on the trans side of the membrane, prior to its release to the environment. PA requires the extracellular chaperone PrsA for efficient folding.
Domain	The molecule is folded into four functional domains. Each domain is required for a particular step in the toxicity process. Domain 1 contains two calcium ions and the proteolytic activation site. Cleavage of the PA monomer releases the subdomain 1a, which is the N-terminal fragment of 20-kDa (PA20). The subdomain 1b is part of the remaining 63-kDa fragment (PA63) and contains the binding sites for LP and EF. Domain 2 is a beta-barrel core containing a large flexible loop that has been implicated in membrane insertion and pore formation. There is a chymotrypsin cleavage site in this loop that is required for toxicity. Domain 3 has a hydrophobic patch thought to be involved in protein-protein interactions. Domain 4 appears to be a separate domain and shows limited contact with the other three domains: it would swing out of the way during membrane insertion. It is required for binding to the receptor; the small loop is involved in receptor recognition. Ref.9 Ref.16
Post-translational modification	Proteolytic activation by furin or a furin-like protease cleaves the protein in two parts, PA-20 and PA-63; the latter is the mature protein. The cleavage occurs at the cell surface and probably in the serum of infected animals as well; both native and cleaved PA are able to bind to the cell receptor. The release of PA20 from the remaining receptor-bound PA63 exposes the binding site for EF and LF, and promotes oligomerization and internalization of the protein.
Miscellaneous	In Ref.16 multiple mutagenesis experiments were performed that showed that the residues present in the small loop of domain 4, and not the ones in the large loop, are involved in receptor recognition. In Ref.23 high-throughput scanning mutagenesis experiments were performed in which all residues of PA-63 were mutated into Cys. Dominantly negative (DN) mutants were all clustered in domain 2. DN mutants prevent the conformational transition of PA-63 from the prepore to the pore state.
Sequence similarities	Belongs to the bacterial binary toxin family.

Ontologies

Keywords
Biological process	Virulence
Cellular component	Secreted
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Toxin
PTM	Cleavage on pair of basic residues
Technical term	3D-structure Complete proteome Plasmid Reference proteome
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-456868,EBI-456868
ANTXR1	Q9H6X2-2	3	EBI-456868,EBI-905659	From a different organism.
ANTXR2	P58335	7	EBI-456868,EBI-456840	From a different organism.
lef	P15917	2	EBI-456868,EBI-456923

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Chain

30 – 764

735

Protective antigen

PRO_0000021996

Chain

30 – 196

167

Protective antigen PA-20

PRO_0000021997

Chain

197 – 764

568

Protective antigen PA-63

PRO_0000021998

Regions

Region

30 – 287

258

Domain 1, calcium-binding; LF and EF binding sites

Region

288 – 516

229

Domain 2, membrane insertion and heptamerization

Region

517 – 624

108

Domain 3, heptamerization

Region

625 – 764

140

Domain 4, binding to the receptor

Sites

Metal binding

206

1

Calcium

Metal binding

208

1

Calcium

Metal binding

210

1

Calcium

Metal binding

217

1

Calcium

Site

196 – 197

2

Cleavage; by furin

Site

343 – 344

2

Cleavage; by chymotrypsin; required for translocation of LF and EF

Site

712

1

Essential for binding to cell receptor

Natural variations

Natural variant

295

1

M → I in strain: PAI.

Natural variant

392

1

N → D in strain: PAI.

Natural variant

560

1

F → L in Sverdlovsk sample.

Natural variant

565

1

P → S in strain: BA1024.

Natural variant

600

1

A → V in strain: BA1024, V770-NP1-R, Carbosap and Ferrara.

Experimental info

Mutagenesis

213

1

P → A: Decrease in the ability to bind to LF and partially toxic at high concentrations. Ref.16 Ref.22

Mutagenesis

216

1

L → A: Decrease in the ability to bind to LF and partially toxic at high concentrations. Ref.16 Ref.22

Mutagenesis

231

1

F → A: Loss of ability to bind to LF and completely nontoxic. Ref.16 Ref.22

Mutagenesis

232

1

L → A: Loss of ability to bind to LF and completely nontoxic. Ref.16 Ref.22

Mutagenesis

234

1

P → A: Loss of ability to bind to LF and completely nontoxic. Ref.16 Ref.22

Mutagenesis

236

1

I → A: Loss of ability to bind to LF and completely nontoxic. Ref.16 Ref.22

Mutagenesis

239

1

I → A: Decrease in the ability to bind to LF and partially toxic at high concentrations. Ref.16 Ref.22

Mutagenesis

255

1

W → A: No effect on LF-binding ability and as toxic as the wild-type. Ref.16 Ref.22

Mutagenesis

265

1

F → A: No effect on LF-binding ability and as toxic as the wild-type. Ref.16 Ref.22

Mutagenesis

289

1

P → A: Reduced toxicity in combination with lethal factor. Decreased membrane insertion and translocation of LF. Ref.16 Ref.19

Mutagenesis

342 – 344

3

FFD → AAA: Decrease in toxicity probably due to slow translocation of LF. Ref.15 Ref.16

Mutagenesis

342 – 343

2

Missing: Loss of toxicity probably due to loss of capability to translocate LF. Ref.16

Mutagenesis

342

1

F → C: Loss of toxicity probably due to loss of capability to translocate LF. Ref.16

Mutagenesis

344

1

D → A: Decrease in toxicity probably due to slow translocation of LF. Ref.15 Ref.16

Mutagenesis

375

1

W → A: Loss of toxicity probably due to faulty membrane insertion or translocation of LF/EF into the cytosol. Ref.16 Ref.17

Mutagenesis

379

1

M → A: No effect. Ref.16 Ref.17

Mutagenesis

381

1

L → A: Loss of toxicity probably due to faulty membrane insertion or translocation of LF/EF into the cytosol. Ref.16 Ref.17

Mutagenesis

393

1

I → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

409

1

T → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

411

1

S → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

422

1

T → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

426

1

K → A or D: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.21 Ref.23

Mutagenesis

428

1

N → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

440

1

Y → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

451

1

N → C: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.23

Mutagenesis

454

1

D → A or K: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.21 Ref.23

Mutagenesis

456

1

F → A: Loss of capability to undergo conformational changes that lead to pore formation and translocation. Ref.16 Ref.21 Ref.23

Mutagenesis

512

1

Q → A: Loss of heptamerization capability. Ref.16 Ref.20

Mutagenesis

541

1

D → A: Loss of heptamerization capability. Ref.16 Ref.20

Mutagenesis

543

1

L → A: Decrease in heptamerization capability. Ref.16 Ref.20

Mutagenesis

581

1

F → A: Loss of toxicity due to defective oligomerization. Ref.16 Ref.18

Mutagenesis

583

1

F → A: Decrease in toxicity due to defective oligomerization. Ref.16 Ref.18

Mutagenesis

591

1

I → A: Loss of toxicity due to defective oligomerization. Ref.16 Ref.18

Mutagenesis

595

1

L → A: Loss of toxicity due to defective oligomerization. Ref.16 Ref.18

Mutagenesis

603

1

I → A: Loss of toxicity due to defective oligomerization. Ref.16 Ref.18

Mutagenesis

621

1

R → A: No effect. Ref.16 Ref.20

Mutagenesis

686

1

N → A: Decrease in toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

708

1

K → A: No effect on toxicity. Ref.16 Ref.24

Mutagenesis

709

1

K → A: Slight decrease in toxicity. Ref.16 Ref.24

Mutagenesis

710

1

Y → A: Great decrease in toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

711

1

N → A: Loss of toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

712

1

D → A: Loss of toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

713

1

K → A: No effect on toxicity. Ref.16 Ref.24

Mutagenesis

714

1

L → A: No effect on toxicity. Ref.16 Ref.24

Mutagenesis

715

1

P → A: Great decrease in toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

716

1

L → A: Decrease in toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

717

1

Y → A: No effect on toxicity. Ref.16 Ref.24

Mutagenesis

718

1

I → A: Decrease in toxicity due to decrease in cell binding. Ref.16 Ref.24

Mutagenesis

719

1

S → A: No effect on toxicity. Ref.16

Mutagenesis

720

1

N → A: No effect on toxicity. Ref.16 Ref.24

Mutagenesis

721

1

P → A: No effect on toxicity. Ref.16 Ref.24

Mutagenesis

722

1

N → A: No effect on toxicity. Ref.16 Ref.24

Sequence conflict

314

1

Q → E in AAA22637. Ref.1

Secondary structure

1

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764

Helix Strand Turn

Details...

Beta strand

47 – 55

9

Beta strand

60 – 71

12

Helix

76 – 78

3

Helix

84 – 86

3

Beta strand

91 – 99

9

Beta strand

104 – 110

7

Helix

113 – 115

3

Beta strand

116 – 120

5

Beta strand

123 – 129

7

Beta strand

135 – 137

3

Beta strand

142 – 150

9

Beta strand

155 – 159

5

Beta strand

162 – 166

5

Beta strand

168 – 170

3

Beta strand

172 – 174

3

Helix

177 – 179

3

Beta strand

186 – 188

3

Beta strand

191 – 193

3

Beta strand

199 – 201

3

Beta strand

210 – 212

3

Helix

214 – 219

6

Beta strand

221 – 225

5

Beta strand

230 – 234

5

Helix

237 – 240

4

Turn

241 – 244

4

Beta strand

255 – 258

4

Beta strand

259 – 262

4

Helix

264 – 269

6

Helix

278 – 281

4

Beta strand

291 – 302

12

Beta strand

318 – 326

9

Beta strand

357 – 363

7

Beta strand

369 – 371

3

Helix

375 – 379

5

Beta strand

386 – 397

12

Beta strand

399 – 401

3

Beta strand

403 – 405

3

Beta strand

410 – 414

5

Turn

415 – 417

3

Beta strand

418 – 423

6

Beta strand

438 – 441

4

Beta strand

448 – 451

4

Beta strand

456 – 458

3

Beta strand

461 – 464

4

Helix

465 – 474

10

Beta strand

476 – 481

6

Beta strand

487 – 492

6

Turn

493 – 496

4

Beta strand

497 – 505

9

Helix

506 – 508

3

Helix

510 – 516

7

Beta strand

517 – 522

6

Turn

524 – 527

4

Beta strand

530 – 535

6

Helix

542 – 546

5

Helix

552 – 560

9

Beta strand

565 – 568

4

Helix

576 – 578

3

Beta strand

579 – 583

5

Helix

585 – 597

13

Helix

603 – 605

3

Turn

607 – 609

3

Beta strand

611 – 613

3

Beta strand

617 – 622

6

Beta strand

625 – 627

3

Beta strand

633 – 636

4

Helix

638 – 644

7

Beta strand

648 – 652

5

Beta strand

655 – 658

4

Helix

662 – 666

5

Beta strand

668 – 676

9

Beta strand

678 – 680

3

Beta strand

682 – 684

3

Helix

689 – 691

3

Beta strand

695 – 697

3

Turn

699 – 701

3

Beta strand

703 – 708

6

Turn

709 – 713

5

Beta strand

723 – 731

9

Helix

732 – 734

3

Beta strand

741 – 743

3

Beta strand

753 – 759

7

Helix

760 – 763

4

Sequences

	Sequence		Length	Mass (Da)
	P13423 [UniParc]. Last modified October 18, 2001. Version 2. Checksum: 3AE1EFBF48FAA03F	FASTA	764	85,811
	10 20 30 40 50 60 MKKRKVLIPL MALSTILVSS TGNLEVIQAE VKQENRLLNE SESSSQGLLG YYFSDLNFQA 70 80 90 100 110 120 PMVVTSSTTG DLSIPSSELE NIPSENQYFQ SAIWSGFIKV KKSDEYTFAT SADNHVTMWV 130 140 150 160 170 180 DDQEVINKAS NSNKIRLEKG RLYQIKIQYQ RENPTEKGLD FKLYWTDSQN KKEVISSDNL 190 200 210 220 230 240 QLPELKQKSS NSRKKRSTSA GPTVPDRDND GIPDSLEVEG YTVDVKNKRT FLSPWISNIH 250 260 270 280 290 300 EKKGLTKYKS SPEKWSTASD PYSDFEKVTG RIDKNVSPEA RHPLVAAYPI VHVDMENIIL 310 320 330 340 350 360 SKNEDQSTQN TDSQTRTISK NTSTSRTHTS EVHGNAEVHA SFFDIGGSVS AGFSNSNSST 370 380 390 400 410 420 VAIDHSLSLA GERTWAETMG LNTADTARLN ANIRYVNTGT APIYNVLPTT SLVLGKNQTL 430 440 450 460 470 480 ATIKAKENQL SQILAPNNYY PSKNLAPIAL NAQDDFSSTP ITMNYNQFLE LEKTKQLRLD 490 500 510 520 530 540 TDQVYGNIAT YNFENGRVRV DTGSNWSEVL PQIQETTARI IFNGKDLNLV ERRIAAVNPS 550 560 570 580 590 600 DPLETTKPDM TLKEALKIAF GFNEPNGNLQ YQGKDITEFD FNFDQQTSQN IKNQLAELNA 610 620 630 640 650 660 TNIYTVLDKI KLNAKMNILI RDKRFHYDRN NIAVGADESV VKEAHREVIN SSTEGLLLNI 670 680 690 700 710 720 DKDIRKILSG YIVEIEDTEG LKEVINDRYD MLNISSLRQD GKTFIDFKKY NDKLPLYISN 730 740 750 760 PNYKVNVYAV TKENTIINPS ENGDTSTNGI KKILIFSKKG YEIG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis." Welkos S.L., Lowe J.R., Eden-Mccutchan F., Vodkin M., Leppla S.H., Schmidt J.J. Gene 69:287-300(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Genetic diversity in the protective antigen gene of Bacillus anthracis." Price L.B., Hugh-Jones M., Jackson P.J., Keim P. J. Bacteriol. 181:2358-2362(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 28, 33, BA1024 and BA1035.
[3]	"Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax." Cohen S., Mendelson I., Altboum Z., Kobiler D., Elhanany E., Bino T., Leitner M., Inbar I., Rosenberg H., Gozes Y., Barak R., Fisher M., Kronman C., Velan B., Shafferman A. Infect. Immun. 68:4549-4558(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: V770-NP1-R / ATCC 14185.
[4]	"Sequence and organization of pXO1, the large Bacillus anthracis plasmid harboring the anthrax toxin genes." Okinaka R.T., Cloud K., Hampton O., Hoffmaster A.R., Hill K.K., Keim P., Koehler T.M., Lamke G., Kumano S., Mahillon J., Manter D., Martinez Y., Ricke D., Svensson R., Jackson P.J. J. Bacteriol. 181:6509-6515(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Sterne.
[5]	"Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis." Read T.D., Salzberg S.L., Pop M., Shumway M.F., Umayam L., Jiang L., Holtzapple E., Busch J.D., Smith K.L., Schupp J.M., Solomon D., Keim P., Fraser C.M. Science 296:2028-2033(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Ames / isolate Florida / A2012.
[6]	"The complete genome sequence of Bacillus anthracis Ames 'Ancestor'." Ravel J., Jiang L., Stanley S.T., Wilson M.R., Decker R.S., Read T.D., Worsham P., Keim P.S., Salzberg S.L., Fraser-Liggett C.M., Rasko D.A. J. Bacteriol. 191:445-446(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Ames ancestor.
[7]	"Sequence analysis of the genes encoding for the major virulence factors of Bacillus anthracis vaccine strain 'Carbosap'." Adone R., Pasquali P., La Rosa G., Marianelli C., Muscillo M., Fasanella A., Francia M., Ciuchini F. J. Appl. Microbiol. 93:117-121(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-751. Strain: Carbosap and Ferrara.
[8]	"Preparation of a positive control DNA for molecular diagnosis of Bacillus anthracis." Inoue S., Noguchi A., Tanabayashi K., Yamada A. Jpn. J. Infect. Dis. 57:29-32(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 195-434. Strain: PAI.
[9]	"The carboxyl-terminal end of protective antigen is required for receptor binding and anthrax toxin activity." Singh Y., Klimpel K.R., Quinn C.P., Chaudhary V.K., Leppla S.H. J. Biol. Chem. 266:15493-15497(1991) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS.
[10]	"Anthrax protective antigen forms oligomers during intoxication of mammalian cells." Milne J.C., Furlong D., Hanna P.C., Wall J.S., Collier R.J. J. Biol. Chem. 269:20607-20612(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION. Strain: Sterne.
[11]	"Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization." Beauregard K.E., Collier R.J., Swanson J.A. Cell. Microbiol. 2:251-258(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[12]	"Regulation of the Bacillus anthracis protective antigen gene: CO2 and a trans-acting element activate transcription from one of two promoters." Koehler T.M., Dai Z., Kaufman-Yarbray M. J. Bacteriol. 176:586-595(1994) [PubMed] [Europe PMC] [Abstract] Cited for: TOXIN REGULATION. Strain: Weybridge.
[13]	"Production of Bacillus anthracis protective antigen is dependent on the extracellular chaperone, PrsA." Williams R.C., Rees M.L., Jacobs M.F., Pragai Z., Thwaite J.E., Baillie L.W., Emmerson P.T., Harwood C.R. J. Biol. Chem. 278:18056-18062(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FOLDING BY PSRA.
[14]	"Binding of anthrax toxin to its receptor is similar to alpha integrin-ligand interactions." Bradley K.A., Mogridge J., Jonah G., Rainey G.J.A., Batty S., Young J.A.T. J. Biol. Chem. 278:49342-49347(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ANTHRAX TOXIN RECEPTOR.
[15]	"The chymotrypsin-sensitive site, FFD315, in anthrax toxin protective antigen is required for translocation of lethal factor." Singh Y., Klimpel K.R., Arora N., Sharma M., Leppla S.H. J. Biol. Chem. 269:29039-29046(1994) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF 342-PHE-PHE-343 AND ASP-344. Strain: Sterne.
[16]	"Identification of a receptor-binding region within domain 4 of the protective antigen component of anthrax toxin." Varughese M., Teixeira A.V., Liu S., Leppla S.H. Infect. Immun. 67:1860-1865(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF DOMAIN 4 LOOPS. Strain: Sterne.
[17]	"Trp 346 and Leu 352 residues in protective antigen are required for the expression of anthrax lethal toxin activity." Batra S., Gupta P., Chauhan V., Singh A., Bhatnagar R. Biochem. Biophys. Res. Commun. 281:186-192(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TRP-375; MET-379 AND LEU-381. Strain: Sterne.
[18]	"Hydrophobic residues Phe552, Phe554, Ile562, Leu566, and Ile574 are required for oligomerization of anthrax protective antigen." Ahuja N., Kumar P., Bhatnagar R. Biochem. Biophys. Res. Commun. 287:542-549(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF PHE-581; PHE-583; ILE-591; LEU-595 AND ILE-603. Strain: Sterne.
[19]	"Role of residues constituting the 2beta1 strand of domain II in the biological activity of anthrax protective antigen." Khanna H., Chopra A.P., Arora N., Chaudhry A., Singh Y. FEMS Microbiol. Lett. 199:27-31(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF PRO-289. Strain: Sterne.
[20]	"Involvement of domain 3 in oligomerization by the protective antigen moiety of anthrax toxin." Mogridge J., Mourez M., Collier R.J. J. Bacteriol. 183:2111-2116(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLN-512; ASP-541; LEU-543 AND ARG-621.
[21]	"Point mutations in anthrax protective antigen that block translocation." Sellman B.R., Nassi S., Collier R.J. J. Biol. Chem. 276:8371-8376(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-426; ASP-454 AND PHE-456.
[22]	"Identification of amino acid residues of anthrax protective antigen involved in binding with lethal factor." Chauhan V., Bhatnagar R. Infect. Immun. 70:4477-4484(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF PRO-213; LEU-216; PHE-231; LEU-232; PRO-234; ILE-236; ILE-239; TRP-255 AND PHE-265. Strain: Sterne.
[23]	"Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis." Mourez M., Yan M., Lacy D.B., Dillon L., Bentsen L., Marpoe A., Maurin C., Hotze E., Wigelsworth D., Pimental R.-A., Ballard J.D., Collier R.J., Tweten R.K. Proc. Natl. Acad. Sci. U.S.A. 100:13803-13808(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ILE-393; THR-409; SER-411; THR-422; LYS-426; ASN-428; TYR-440; ASN-451; ASP-454 AND PHE-456.
[24]	"Alanine-scanning mutations in domain 4 of anthrax toxin protective antigen reveal residues important for binding to the cellular receptor and to a neutralizing monoclonal antibody." Rosovitz M.J., Schuck P., Varughese M., Chopra A.P., Mehra V., Singh Y., McGinnis L.M., Leppla S.H. J. Biol. Chem. 278:30936-30944(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-686; LYS-708; LYS-709; TYR-710; ASN-711; ASP-712; LYS-713; LEU-714; PRO-715; LEU-716; TYR-717; ILE-718; ASN-720; PRO-721 AND ASN-722.
[25]	"Crystal structure of the anthrax toxin protective antigen." Petosa C., Collier R.J., Klimpel K.R., Leppla S.H., Liddington R.C. Nature 385:833-838(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[26]	"Crystal structure of a complex between anthrax toxin and its host cell receptor." Santelli E., Bankston L.A., Leppla S.H., Liddington R.C. Nature 430:905-908(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 30-764 IN COMPLEX WITH ANTXR2.
[27]	"Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation." Lacy D.B., Wigelsworth D.J., Melnyk R.A., Harrison S.C., Collier R.J. Proc. Natl. Acad. Sci. U.S.A. 101:13147-13151(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (4.3 ANGSTROMS) OF 203-764 IN COMPLEX WITH ANTXR2.
[28]	"Anthrax." Mock M., Fouet A. Annu. Rev. Microbiol. 55:647-671(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22589 Genomic DNA. Translation: AAA22637.1.
AF306778 Genomic DNA. Translation: AAG24446.1.
AF306779 Genomic DNA. Translation: AAG24447.1.
AF306780 Genomic DNA. Translation: AAG24448.1.
AF306781 Genomic DNA. Translation: AAG24449.1.
AF306782 Genomic DNA. Translation: AAG24450.1.
AF306783 Genomic DNA. Translation: AAG24451.1.
AF268967 Genomic DNA. Translation: AAF86457.1.
AF065404 Genomic DNA. Translation: AAD32414.1.
AE011190 Genomic DNA. Translation: AAM26109.1.
AE017336 Genomic DNA. Translation: AAT28905.2.
AJ413936 Genomic DNA. Translation: CAC93934.1.
AJ413937 Genomic DNA. Translation: CAC93935.1.
AB125961 Genomic DNA. Translation: BAD14937.1.

PIR

I39934.

RefSeq

NP_052806.1. NC_001496.1.
NP_652920.1. NC_003980.1.
YP_016495.2. NC_007322.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ACC	X-ray	2.10	A	30-764	[»]
1T6B	X-ray	2.50	X	30-764	[»]
1TX5	model	-	C	30-764	[»]
1TZN	X-ray	4.30	A/B/C/D/E/F/G/H/I/J/K/L/M/O	203-764	[»]
1TZO	X-ray	3.60	A/B/C/D/E/F/G/H/I/J/K/L/M/O	203-764	[»]
1V36	model	-	A/B/C/D/E/F/G	197-764	[»]
3ETB	X-ray	3.80	J/K/L/M	621-764	[»]
3INO	X-ray	1.95	A/B	624-764	[»]
3KWV	X-ray	3.10	A/B/D/E	197-764	[»]
3MHZ	X-ray	1.70	A	30-764	[»]
3Q8A	X-ray	3.13	A	30-764	[»]
3Q8B	X-ray	2.00	A	30-764	[»]
3Q8C	X-ray	2.85	A	30-764	[»]
3Q8E	X-ray	2.10	A	30-764	[»]
3Q8F	X-ray	2.10	A	30-764	[»]
3TEW	X-ray	1.45	A	30-764	[»]
3TEX	X-ray	1.70	A	30-764	[»]
3TEY	X-ray	2.12	A	30-764	[»]
3TEZ	X-ray	1.83	A	30-764	[»]
4EE2	X-ray	1.91	A	30-764	[»]

ProteinModelPortal

P13423.

SMR

P13423. Positions 45-764.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29841N.

IntAct

P13423. 15 interactions.

MINT

MINT-7014733.

STRING

261594.GBAA_pXO1_0164.

Protein family/group databases

TCDB

1.C.42.1.1. channel-forming bacillus anthracis protective antigen (BAPA) family.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAM26109; AAM26109; BX_A0164.
AAT28905; AAT28905; GBAA_pXO1_0164.

GeneID

1158723.
2820165.
3361714.

KEGG

bar:GBAA_pXO1_0164.

PATRIC

24662127. VBIBacAnt106580_0153.

Phylogenomic databases

eggNOG

NOG284171.

HOGENOM

HOG000034566.

KO

K11030.

OMA

ESTISNT.

ProtClustDB

CLSK687634.

Enzyme and pathway databases

BioCyc

BANT261594:GJ7F-5750-MONOMER.

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.

Family and domain databases

Gene3D

3.10.20.110. 1 hit.

InterPro

IPR003896. Bacterial_exotoxin_B.
IPR023125. Bacterial_exotoxin_B_Fd-like.
IPR011658. PA14.
[Graphical view]

Pfam

PF03495. Binary_toxB. 1 hit.
PF07691. PA14. 1 hit.
[Graphical view]

PRINTS

PR01391. BINARYTOXINB.

SMART

SM00758. PA14. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5352.

EvolutionaryTrace

P13423.

PMAP-CutDB

P13423.

Entry information

Entry name

PAG_BACAN

Accession

Primary (citable) accession number: P13423
Secondary accession number(s): Q937W2 , Q937W3, Q9F5R7, Q9KH69, Q9RQU2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	October 18, 2001
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program