Protective antigen

Details

Name
Protective antigen
Synonyms
  • Anthrax toxins translocating protein
  • PA
  • PA-83
  • PA83
  • pag
Gene Name
pagA
Organism
Bacillus anthracis
Amino acid sequence
>lcl|BSEQ0013294|Protective antigen
MKKRKVLIPLMALSTILVSSTGNLEVIQAEVKQENRLLNESESSSQGLLGYYFSDLNFQA
PMVVTSSTTGDLSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWV
DDQEVINKASNSNKIRLEKGRLYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDNL
QLPELKQKSSNSRKKRSTSAGPTVPDRDNDGIPDSLEVEGYTVDVKNKRTFLSPWISNIH
EKKGLTKYKSSPEKWSTASDPYSDFEKVTGRIDKNVSPEARHPLVAAYPIVHVDMENIIL
SKNEDQSTQNTDSQTRTISKNTSTSRTHTSEVHGNAEVHASFFDIGGSVSAGFSNSNSST
VAIDHSLSLAGERTWAETMGLNTADTARLNANIRYVNTGTAPIYNVLPTTSLVLGKNQTL
ATIKAKENQLSQILAPNNYYPSKNLAPIALNAQDDFSSTPITMNYNQFLELEKTKQLRLD
TDQVYGNIATYNFENGRVRVDTGSNWSEVLPQIQETTARIIFNGKDLNLVERRIAAVNPS
DPLETTKPDMTLKEALKIAFGFNEPNGNLQYQGKDITEFDFNFDQQTSQNIKNQLAELNA
TNIYTVLDKIKLNAKMNILIRDKRFHYDRNNIAVGADESVVKEAHREVINSSTEGLLLNI
DKDIRKILSGYIVEIEDTEGLKEVINDRYDMLNISSLRQDGKTFIDFKKYNDKLPLYISN
PNYKVNVYAVTKENTIINPSENGDTSTNGIKKILIFSKKGYEIG
Number of residues
764
Molecular Weight
85810.325
Theoretical pI
Not Available
GO Classification
Functions
identical protein binding / metal ion binding
Processes
negative regulation of gene expression / negative regulation of MAPK cascade / negative regulation of protein phosphorylation / negative regulation of transcription from RNA polymerase II promoter / pathogenesis / positive regulation of apoptotic process in other organism / protein homooligomerization / proteolysis in other organism / regulation of establishment of endothelial barrier / regulation of proteasomal protein catabolic process
Components
endosome membrane / extracellular region / extracellular space / plasma membrane
General Function
Metal ion binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0013295|Protective antigen (pagA)
ATGAAAAAACGAAAAGTGTTAATACCATTAATGGCATTGTCTACGATATTAGTTTCAAGC
ACAGGTAATTTAGAGGTGATTCAGGCAGAAGTTAAACAGGAGAACCGGTTATTAAATGAA
TCAGAATCAAGTTCCCAGGGGTTACTAGGATACTATTTTAGTGATTTGAATTTTCAAGCA
CCCATGGTGGTTACCTCTTCTACTACAGGGGATTTATCTATTCCTAGTTCTGAGTTAGAA
AATATTCCATCGGAAAACCAATATTTTCAATCTGCTATTTGGTCAGGATTTATCAAAGTT
AAGAAGAGTGATGAATATACATTTGCTACTTCCGCTGATAATCATGTAACAATGTGGGTA
GATGACCAAGAAGTGATTAATAAAGCTTCTAATTCTAACAAAATCAGATTAGAAAAAGGA
AGATTATATCAAATAAAAATTCAATATCAACGAGAAAATCCTACTGAAAAAGGATTGGAT
TTCAAGTTGTACTGGACCGATTCTCAAAATAAAAAAGAAGTGATTTCTAGTGATAACTTA
CAATTGCCAGAATTAAAACAAAAATCTTCGAACTCAAGAAAAAAGCGAAGTACAAGTGCT
GGACCTACGGTTCCAGACCGTGACAATGATGGAATCCCTGATTCATTAGAGGTAGAAGGA
TATACGGTTGATGTCAAAAATAAAAGAACTTTTCTTTCACCATGGATTTCTAATATTCAT
GAAAAGAAAGGATTAACCAAATATAAATCATCTCCTGAAAAATGGAGCACGGCTTCTGAT
CCGTACAGTGATTTCGAAAAGGTTACAGGACGGATTGATAAGAATGTATCACCAGAGGCA
AGACACCCCCTTGTGGCAGCTTATCCGATTGTACATGTAGATATGGAGAATATTATTCTC
TCAAAAAATGAGGATCAATCCACACAGAATACTGATAGTCAAACGAGAACAATAAGTAAA
AATACTTCTACAAGTAGGACACATACTAGTGAAGTACATGGAAATGCAGAAGTGCATGCG
TCGTTCTTTGATATTGGTGGGAGTGTATCTGCAGGATTTAGTAATTCGAATTCAAGTACG
GTCGCAATTGATCATTCACTATCTCTAGCAGGGGAAAGAACTTGGGCTGAAACAATGGGT
TTAAATACCGCTGATACAGCAAGATTAAATGCCAATATTAGATATGTAAATACTGGGACG
GCTCCAATCTACAACGTGTTACCAACGACTTCGTTAGTGTTAGGAAAAAATCAAACACTC
GCGACAATTAAAGCTAAGGAAAACCAATTAAGTCAAATACTTGCACCTAATAATTATTAT
CCTTCTAAAAACTTGGCGCCAATCGCATTAAATGCACAAGACGATTTCAGTTCTACTCCA
ATTACAATGAATTACAATCAATTTCTTGAGTTAGAAAAAACGAAACAATTAAGATTAGAT
ACGGATCAAGTATATGGGAATATAGCAACATACAATTTTGAAAATGGAAGAGTGAGGGTG
GATACAGGCTCGAACTGGAGTGAAGTGTTACCGCAAATTCAAGAAACAACTGCACGTATC
ATTTTTAATGGAAAAGATTTAAATCTGGTAGAAAGGCGGATAGCGGCGGTTAATCCTAGT
GATCCATTAGAAACGACTAAACCGGATATGACATTAAAAGAAGCCCTTAAAATAGCATTT
GGATTTAACGAACCGAATGGAAACTTACAATATCAAGGGAAAGACATAACCGAATTTGAT
TTTAATTTCGATCAACAAACATCTCAAAATATCAAGAATCAGTTAGCGGAATTAAACGCA
ACTAACATATATACTGTATTAGATAAAATCAAATTAAATGCAAAAATGAATATTTTAATA
AGAGATAAACGTTTTCATTATGATAGAAATAACATAGCAGTTGGGGCGGATGAGTCAGTA
GTTAAGGAGGCTCATAGAGAAGTAATTAATTCGTCAACAGAGGGATTATTGTTAAATATT
GATAAGGATATAAGAAAAATATTATCAGGTTATATTGTAGAAATTGAAGATACTGAAGGG
CTTAAAGAAGTTATAAATGACAGATATGATATGTTGAATATTTCTAGTTTACGGCAAGAT
GGAAAAACATTTATAGATTTTAAAAAATATAATGATAAATTACCGTTATATATAAGTAAT
CCCAATTATAAGGTAAATGTATATGCTGTTACTAAAGAAAACACTATTATTAATCCTAGT
GAGAATGGGGATACTAGTACCAACGGGATCAAGAAAATTTTAATCTTTTCTAAAAAAGGC
TATGAGATAGGATAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP13423
UniProtKB Entry NamePAG_BACAN
General References
  1. Welkos SL, Lowe JR, Eden-McCutchan F, Vodkin M, Leppla SH, Schmidt JJ: Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis. Gene. 1988 Sep 30;69(2):287-300. [Article]
  2. Price LB, Hugh-Jones M, Jackson PJ, Keim P: Genetic diversity in the protective antigen gene of Bacillus anthracis. J Bacteriol. 1999 Apr;181(8):2358-62. [Article]
  3. 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: Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax. Infect Immun. 2000 Aug;68(8):4549-58. [Article]
  4. Okinaka RT, Cloud K, Hampton O, Hoffmaster AR, Hill KK, Keim P, Koehler TM, Lamke G, Kumano S, Mahillon J, Manter D, Martinez Y, Ricke D, Svensson R, Jackson PJ: Sequence and organization of pXO1, the large Bacillus anthracis plasmid harboring the anthrax toxin genes. J Bacteriol. 1999 Oct;181(20):6509-15. [Article]
  5. Read TD, Salzberg SL, Pop M, Shumway M, Umayam L, Jiang L, Holtzapple E, Busch JD, Smith KL, Schupp JM, Solomon D, Keim P, Fraser CM: Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis. Science. 2002 Jun 14;296(5575):2028-33. Epub 2002 May 9. [Article]
  6. Ravel J, Jiang L, Stanley ST, Wilson MR, Decker RS, Read TD, Worsham P, Keim PS, Salzberg SL, Fraser-Liggett CM, Rasko DA: The complete genome sequence of Bacillus anthracis Ames "Ancestor". J Bacteriol. 2009 Jan;191(1):445-6. doi: 10.1128/JB.01347-08. Epub 2008 Oct 24. [Article]
  7. Adone R, Pasquali P, La Rosa G, Marianelli C, Muscillo M, Fasanella A, Francia M, Ciuchini F: Sequence analysis of the genes encoding for the major virulence factors of Bacillus anthracis vaccine strain 'Carbosap'. J Appl Microbiol. 2002;93(1):117-21. [Article]
  8. Inoue S, Noguchi A, Tanabayashi K, Yamada A: Preparation of a positive control DNA for molecular diagnosis of Bacillus anthracis. Jpn J Infect Dis. 2004 Feb;57(1):29-32. [Article]
  9. Singh Y, Klimpel KR, Quinn CP, Chaudhary VK, Leppla SH: The carboxyl-terminal end of protective antigen is required for receptor binding and anthrax toxin activity. J Biol Chem. 1991 Aug 15;266(23):15493-7. [Article]
  10. Milne JC, Furlong D, Hanna PC, Wall JS, Collier RJ: Anthrax protective antigen forms oligomers during intoxication of mammalian cells. J Biol Chem. 1994 Aug 12;269(32):20607-12. [Article]
  11. Beauregard KE, Collier RJ, Swanson JA: Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization. Cell Microbiol. 2000 Jun;2(3):251-8. [Article]
  12. Koehler TM, Dai Z, Kaufman-Yarbray M: Regulation of the Bacillus anthracis protective antigen gene: CO2 and a trans-acting element activate transcription from one of two promoters. J Bacteriol. 1994 Feb;176(3):586-95. [Article]
  13. Williams RC, Rees ML, Jacobs MF, Pragai Z, Thwaite JE, Baillie LW, Emmerson PT, Harwood CR: Production of Bacillus anthracis protective antigen is dependent on the extracellular chaperone, PrsA. J Biol Chem. 2003 May 16;278(20):18056-62. Epub 2003 Feb 26. [Article]
  14. Bradley KA, Mogridge J, Jonah G, Rainey A, Batty S, Young JA: Binding of anthrax toxin to its receptor is similar to alpha integrin-ligand interactions. J Biol Chem. 2003 Dec 5;278(49):49342-7. Epub 2003 Sep 24. [Article]
  15. Singh Y, Klimpel KR, Arora N, Sharma M, Leppla SH: The chymotrypsin-sensitive site, FFD315, in anthrax toxin protective antigen is required for translocation of lethal factor. J Biol Chem. 1994 Nov 18;269(46):29039-46. [Article]
  16. Varughese M, Teixeira AV, Liu S, Leppla SH: Identification of a receptor-binding region within domain 4 of the protective antigen component of anthrax toxin. Infect Immun. 1999 Apr;67(4):1860-5. [Article]
  17. Batra S, Gupta P, Chauhan V, Singh A, Bhatnagar R: Trp 346 and Leu 352 residues in protective antigen are required for the expression of anthrax lethal toxin activity. Biochem Biophys Res Commun. 2001 Feb 16;281(1):186-92. [Article]
  18. Ahuja N, Kumar P, Bhatnagar R: Hydrophobic residues Phe552, Phe554, Ile562, Leu566, and Ile574 are required for oligomerization of anthrax protective antigen. Biochem Biophys Res Commun. 2001 Sep 21;287(2):542-9. [Article]
  19. Khanna H, Chopra AP, Arora N, Chaudhry A, Singh Y: Role of residues constituting the 2beta1 strand of domain II in the biological activity of anthrax protective antigen. FEMS Microbiol Lett. 2001 May 15;199(1):27-31. [Article]
  20. Mogridge J, Mourez M, Collier RJ: Involvement of domain 3 in oligomerization by the protective antigen moiety of anthrax toxin. J Bacteriol. 2001 Mar;183(6):2111-6. [Article]
  21. Sellman BR, Nassi S, Collier RJ: Point mutations in anthrax protective antigen that block translocation. J Biol Chem. 2001 Mar 16;276(11):8371-6. Epub 2000 Dec 11. [Article]
  22. Chauhan V, Bhatnagar R: Identification of amino acid residues of anthrax protective antigen involved in binding with lethal factor. Infect Immun. 2002 Aug;70(8):4477-84. [Article]
  23. Mourez M, Yan M, Lacy DB, Dillon L, Bentsen L, Marpoe A, Maurin C, Hotze E, Wigelsworth D, Pimental RA, Ballard JD, Collier RJ, Tweten RK: Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13803-8. Epub 2003 Nov 17. [Article]
  24. Rosovitz MJ, Schuck P, Varughese M, Chopra AP, Mehra V, Singh Y, McGinnis LM, Leppla SH: 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. J Biol Chem. 2003 Aug 15;278(33):30936-44. Epub 2003 May 27. [Article]
  25. Petosa C, Collier RJ, Klimpel KR, Leppla SH, Liddington RC: Crystal structure of the anthrax toxin protective antigen. Nature. 1997 Feb 27;385(6619):833-8. [Article]
  26. Santelli E, Bankston LA, Leppla SH, Liddington RC: Crystal structure of a complex between anthrax toxin and its host cell receptor. Nature. 2004 Aug 19;430(7002):905-8. Epub 2004 Jul 4. [Article]
  27. Lacy DB, Wigelsworth DJ, Melnyk RA, Harrison SC, Collier RJ: Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13147-51. Epub 2004 Aug 23. [Article]
  28. Mock M, Fouet A: Anthrax. Annu Rev Microbiol. 2001;55:647-71. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08902RaxibacumabapprovedyesantibodyDetails
DB09057Anthrax immune globulin humanapprovedyesantibodyDetails