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1.C.11.1.4
Bifunctional adenylate cyclase-haemolysin toxin precursor, CyaA.  Although homologous, HlyA (1.C.11.1.3) and CyaA  exhibit different modes of permeabilization (Fiser and Konopásek 2009).  A pore model comprising three alpha2-loop-alpha3 hairpins suggested that Gly530XXGly533XXXGly537  in TMS2 could function in toxin oligomerization (Juntapremjit et al. 2015).  Structural integrity of TMSs 1, 2, 3 and 5, but not 4, is important for haemolytic activity, particularly for transmembrane helices 2 and 3 that might form the pore (Powthongchin and Angsuthanasombat 2009). CyaA forms small cation-selective membrane pores that permeabilize cells for potassium efflux, contributing to cytotoxicity of CyaA and eventually provoking colloid-osmotic cell lysis (Wald et al. 2016).  The toxin penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into the cytosol its N-terminal adenylate cyclase enzyme domain (~400 residues). In parallel, the ~1300 residue-long RTX hemolysin moiety of CyaA permeabilizes target cell membranes for efflux of cytosolic potassium ions (Svedova et al. 2016).  Positively-charged side-chains substituted at positions Gln574 and Glu581 in the pore-lining alpha3 enhance hemolytic activity and ion-channel opening, mimicing the highly-active RTX (repeat-in-toxin) cytolysins (Kurehong et al. 2017).

Accession Number:P15318
Protein Name:CyaA or Cya
Length:1706
Molecular Weight:177521.00
Species:Bordetella pertussis [520]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Secreted1
Substrate small molecules

Cross database links:

HEGENOM: HBG353287
RefSeq: NP_879578.1   
Entrez Gene ID: 2664492   
Pfam: PF03497    PF00353    PF02382   
BioCyc: BPER257313:BP0760-MONOMER   
KEGG: bpe:BP0760   

Gene Ontology

GO:0005576 C:extracellular region
GO:0005524 F:ATP binding
GO:0005509 F:calcium ion binding
GO:0008294 F:calcium- and calmodulin-responsive adenylat...
GO:0005516 F:calmodulin binding
GO:0006171 P:cAMP biosynthetic process
GO:0019835 P:cytolysis
GO:0019836 P:hemolysis by symbiont of host erythrocytes
GO:0009405 P:pathogenesis

References (9)

[1] “The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli.”  Glaser P.et.al.   2897067
[2] “Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.”  Parkhill J.et.al.   12910271
[3] “Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis.”  Glaser P.et.al.   2905265
[4] “Isolation and characterization of catalytic and calmodulin-binding domains of Bordetella pertussis adenylate cyclase.”  Munier H.et.al.   2007407
[5] “Identification of residues essential for catalysis and binding of calmodulin in Bordetella pertussis adenylate cyclase by site-directed mutagenesis.”  Glaser P.et.al.   2542030
[6] “Functional consequences of single amino acid substitutions in calmodulin-activated adenylate cyclase of Bordetella pertussis.”  Glaser P.et.al.   2050107
[7] “Phylogeny of adenylyl cyclases.”  Danchin A.et.al.   8418825
[8] “Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis.”  Hackett M.et.al.   7939682
[9] “The conserved lysine 860 in the additional fatty-acylation site of Bordetella pertussis adenylate cyclase is crucial for toxin function independently of its acylation status.”  Basar T.et.al.   10196151
Structure:
1YRT   1YRU   1ZOT   2COL     

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MQQSHQAGYA NAADRESGIP AAVLDGIKAV AKEKNATLMF RLVNPHSTSL IAEGVATKGL 
61:	GVHAKSSDWG LQAGYIPVNP NLSKLFGRAP EVIARADNDV NSSLAHGHTA VDLTLSKERL 
121:	DYLRQAGLVT GMADGVVASN HAGYEQFEFR VKETSDGRYA VQYRRKGGDD FEAVKVIGNA 
181:	AGIPLTADID MFAIMPHLSN FRDSARSSVT SGDSVTDYLA RTRRAASEAT GGLDRERIDL 
241:	LWKIARAGAR SAVGTEARRQ FRYDGDMNIG VITDFELEVR NALNRRAHAV GAQDVVQHGT 
301:	EQNNPFPEAD EKIFVVSATG ESQMLTRGQL KEYIGQQRGE GYVFYENRAY GVAGKSLFDD 
361:	GLGAAPGVPS GRSKFSPDVL ETVPASPGLR RPSLGAVERQ DSGYDSLDGV GSRSFSLGEV 
421:	SDMAAVEAAE LEMTRQVLHA GARQDDAEPG VSGASAHWGQ RALQGAQAVA AAQRLVHAIA 
481:	LMTQFGRAGS TNTPQEAASL SAAVFGLGEA SSAVAETVSG FFRGSSRWAG GFGVAGGAMA 
541:	LGGGIAAAVG AGMSLTDDAP AGQKAAAGAE IALQLTGGTV ELASSIALAL AAARGVTSGL 
601:	QVAGASAGAA AGALAAALSP MEIYGLVQQS HYADQLDKLA QESSAYGYEG DALLAQLYRD 
661:	KTAAEGAVAG VSAVLSTVGA AVSIAAAASV VGAPVAVVTS LLTGALNGIL RGVQQPIIEK 
721:	LANDYARKID ELGGPQAYFE KNLQARHEQL ANSDGLRKML ADLQAGWNAS SVIGVQTTEI 
781:	SKSALELAAI TGNADNLKSV DVFVDRFVQG ERVAGQPVVL DVAAGGIDIA SRKGERPALT 
841:	FITPLAAPGE EQRRRTKTGK SEFTTFVEIV GKQDRWRIRD GAADTTIDLA KVVSQLVDAN 
901:	GVLKHSIKLD VIGGDGDDVV LANASRIHYD GGAGTNTVSY AALGRQDSIT VSADGERFNV 
961:	RKQLNNANVY REGVATQTTA YGKRTENVQY RHVELARVGQ LVEVDTLEHV QHIIGGAGND 
1021:	SITGNAHDNF LAGGSGDDRL DGGAGNDTLV GGEGQNTVIG GAGDDVFLQD LGVWSNQLDG 
1081:	GAGVDTVKYN VHQPSEERLE RMGDTGIHAD LQKGTVEKWP ALNLFSVDHV KNIENLHGSR 
1141:	LNDRIAGDDQ DNELWGHDGN DTIRGRGGDD ILRGGLGLDT LYGEDGNDIF LQDDETVSDD 
1201:	IDGGAGLDTV DYSAMIHPGR IVAPHEYGFG IEADLSREWV RKASALGVDY YDNVRNVENV 
1261:	IGTSMKDVLI GDAQANTLMG QGGDDTVRGG DGDDLLFGGD GNDMLYGDAG NDTLYGGLGD 
1321:	DTLEGGAGND WFGQTQAREH DVLRGGDGVD TVDYSQTGAH AGIAAGRIGL GILADLGAGR 
1381:	VDKLGEAGSS AYDTVSGIEN VVGTELADRI TGDAQANVLR GAGGADVLAG GEGDDVLLGG 
1441:	DGDDQLSGDA GRDRLYGEAG DDWFFQDAAN AGNLLDGGDG RDTVDFSGPG RGLDAGAKGV 
1501:	FLSLGKGFAS LMDEPETSNV LRNIENAVGS ARDDVLIGDA GANVLNGLAG NDVLSGGAGD 
1561:	DVLLGDEGSD LLSGDAGNDD LFGGQGDDTY LFGVGYGHDT IYESGGGHDT IRINAGADQL 
1621:	WFARQGNDLE IRILGTDDAL TVHDWYRDAD HRVEIIHAAN QAVDQAGIEK LVEAMAQYPD 
1681:	PGAAAAAPPA ARVPDTLMQS LAVNWR