CYAA_BORBR
ID CYAA_BORBR Reviewed; 1706 AA.
AC Q57506; O05179;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2003, sequence version 4.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Bifunctional hemolysin/adenylate cyclase;
DE AltName: Full=AC-HLY;
DE AltName: Full=ACT;
DE AltName: Full=Cyclolysin;
DE Contains:
DE RecName: Full=Calmodulin-sensitive adenylate cyclase;
DE EC=4.6.1.1 {ECO:0000250|UniProtKB:P0DKX7};
DE AltName: Full=ATP pyrophosphate-lyase;
DE AltName: Full=Adenylyl cyclase;
DE Contains:
DE RecName: Full=Hemolysin;
DE Flags: Precursor;
GN Name=cya; Synonyms=cyaA; OrderedLocusNames=BB0324;
OS Bordetella bronchiseptica (strain ATCC BAA-588 / NCTC 13252 / RB50)
OS (Alcaligenes bronchisepticus).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Alcaligenaceae; Bordetella.
OX NCBI_TaxID=257310;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CIP 9.73;
RX PubMed=7557410; DOI=10.1016/0378-1119(95)00339-8;
RA Betsou F., Sismeiro O., Danchin A., Guiso N.;
RT "Cloning and sequence of the Bordetella bronchiseptica adenylate cyclase-
RT hemolysin-encoding gene: comparison with the Bordetella pertussis gene.";
RL Gene 162:165-166(1995).
RN [2]
RP SEQUENCE REVISION TO 1556-1559.
RA Danchin A., Boursaux-Eude C.;
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-588 / NCTC 13252 / RB50;
RX PubMed=12910271; DOI=10.1038/ng1227;
RA Parkhill J., Sebaihia M., Preston A., Murphy L.D., Thomson N.R.,
RA Harris D.E., Holden M.T.G., Churcher C.M., Bentley S.D., Mungall K.L.,
RA Cerdeno-Tarraga A.-M., Temple L., James K.D., Harris B., Quail M.A.,
RA Achtman M., Atkin R., Baker S., Basham D., Bason N., Cherevach I.,
RA Chillingworth T., Collins M., Cronin A., Davis P., Doggett J., Feltwell T.,
RA Goble A., Hamlin N., Hauser H., Holroyd S., Jagels K., Leather S.,
RA Moule S., Norberczak H., O'Neil S., Ormond D., Price C., Rabbinowitsch E.,
RA Rutter S., Sanders M., Saunders D., Seeger K., Sharp S., Simmonds M.,
RA Skelton J., Squares R., Squares S., Stevens K., Unwin L., Whitehead S.,
RA Barrell B.G., Maskell D.J.;
RT "Comparative analysis of the genome sequences of Bordetella pertussis,
RT Bordetella parapertussis and Bordetella bronchiseptica.";
RL Nat. Genet. 35:32-40(2003).
CC -!- FUNCTION: Bifunctional adenylate cyclase toxin-hemolysin that plays a
CC crucial role in host colonization. It causes whooping cough by acting
CC on mammalian cells by elevating cAMP-concentration and thus disrupts
CC normal cell function. {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- FUNCTION: [Calmodulin-sensitive adenylate cyclase]: Adenylate cyclase
CC that is activated by host intracellular calmodulin and catalyzes un-
CC regulated conversion of ATP to cAMP, thereby impairing microbicidal
CC functions of immune effector cells and inducing apoptosis of lung
CC macrophages. {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- FUNCTION: [Hemolysin]: Hemolysin that forms small cation-selective
CC membrane channels, leading to hemolytic activity (By similarity). The
CC hemolytic activity of CyaA is weak compared with that of the HlyA of
CC E.coli (By similarity). {ECO:0000250|UniProtKB:J7QLC0,
CC ECO:0000250|UniProtKB:P0DKX7}.
CC -!- CATALYTIC ACTIVITY: [Calmodulin-sensitive adenylate cyclase]:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000250|UniProtKB:P0DKX7};
CC -!- ACTIVITY REGULATION: [Calmodulin-sensitive adenylate cyclase]:
CC Activated by host calmodulin. {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- SUBCELLULAR LOCATION: [Hemolysin]: Host cell membrane
CC {ECO:0000250|UniProtKB:P0DKX7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- DOMAIN: The Gly-rich region is probably involved in binding calcium,
CC which is required for target cell-binding or cytolytic activity.
CC -!- PTM: Released in a processed form. {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- PTM: [Hemolysin]: Palmitoylated at Lys-860 and Lys-983 by CyaC. The
CC toxin only becomes active when modified in position Lys-983:
CC palmitoylation is required for efficient membrane insertion and pore
CC formation of the acylated Hemolysin chain.
CC {ECO:0000250|UniProtKB:P0DKX7}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the adenylyl cyclase
CC class-2 family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the RTX prokaryotic
CC toxin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAE30822.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; Z37112; CAA85481.2; -; Genomic_DNA.
DR EMBL; BX640437; CAE30822.1; ALT_INIT; Genomic_DNA.
DR PIR; S51672; S51672.
DR AlphaFoldDB; Q57506; -.
DR BMRB; Q57506; -.
DR SMR; Q57506; -.
DR STRING; 257310.BB0324; -.
DR PRIDE; Q57506; -.
DR EnsemblBacteria; CAE30822; CAE30822; BB0324.
DR KEGG; bbr:BB0324; -.
DR eggNOG; COG2931; Bacteria.
DR HOGENOM; CLU_239696_0_0_4; -.
DR OrthoDB; 50309at2; -.
DR Proteomes; UP000001027; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008294; F:calcium- and calmodulin-responsive adenylate cyclase activity; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006171; P:cAMP biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR Gene3D; 2.150.10.10; -; 5.
DR Gene3D; 3.90.1760.10; -; 1.
DR InterPro; IPR035099; Anthrax_toxin_C-terminal.
DR InterPro; IPR005165; Anthrax_toxin_edema_cen.
DR InterPro; IPR037017; Anthrax_toxin_edema_cen_sf.
DR InterPro; IPR010566; Haemolys_ca-bd.
DR InterPro; IPR018511; Hemolysin-typ_Ca-bd_CS.
DR InterPro; IPR001343; Hemolysn_Ca-bd.
DR InterPro; IPR018504; RTX_N.
DR InterPro; IPR003995; RTX_toxin_determinant-A.
DR InterPro; IPR011049; Serralysin-like_metalloprot_C.
DR Pfam; PF03497; Anthrax_toxA; 1.
DR Pfam; PF06594; HCBP_related; 1.
DR Pfam; PF00353; HemolysinCabind; 8.
DR Pfam; PF02382; RTX; 1.
DR PRINTS; PR01488; RTXTOXINA.
DR SUPFAM; SSF51120; SSF51120; 5.
DR SUPFAM; SSF81298; SSF81298; 1.
DR PROSITE; PS00330; HEMOLYSIN_CALCIUM; 5.
PE 3: Inferred from homology;
KW ATP-binding; Calcium; Calmodulin-binding; cAMP biosynthesis; Cytolysis;
KW Hemolysis; Host cell membrane; Host membrane; Lipoprotein; Lyase; Membrane;
KW Myristate; Nucleotide-binding; Palmitate; Repeat; Secreted; Toxin;
KW Transmembrane; Virulence; Whooping cough.
FT CHAIN 1..312
FT /note="Calmodulin-sensitive adenylate cyclase"
FT /id="PRO_0000001318"
FT CHAIN 313..1706
FT /note="Hemolysin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000001319"
FT REPEAT 1014..1031
FT /note="Hemolysin-type calcium-binding 1"
FT REPEAT 1032..1049
FT /note="Hemolysin-type calcium-binding 2"
FT REPEAT 1050..1067
FT /note="Hemolysin-type calcium-binding 3"
FT REPEAT 1155..1172
FT /note="Hemolysin-type calcium-binding 4"
FT REPEAT 1173..1190
FT /note="Hemolysin-type calcium-binding 5"
FT REPEAT 1279..1296
FT /note="Hemolysin-type calcium-binding 6"
FT REPEAT 1297..1314
FT /note="Hemolysin-type calcium-binding 7"
FT REPEAT 1315..1332
FT /note="Hemolysin-type calcium-binding 8"
FT REPEAT 1335..1352
FT /note="Hemolysin-type calcium-binding 9"
FT REPEAT 1411..1428
FT /note="Hemolysin-type calcium-binding 10"
FT REPEAT 1429..1446
FT /note="Hemolysin-type calcium-binding 11"
FT REPEAT 1447..1464
FT /note="Hemolysin-type calcium-binding 12"
FT REPEAT 1468..1484
FT /note="Hemolysin-type calcium-binding 13"
FT REPEAT 1537..1554
FT /note="Hemolysin-type calcium-binding 14"
FT REPEAT 1555..1572
FT /note="Hemolysin-type calcium-binding 15"
FT REPEAT 1573..1590
FT /note="Hemolysin-type calcium-binding 16"
FT REPEAT 1603..1620
FT /note="Hemolysin-type calcium-binding 17"
FT REGION 1..399
FT /note="A, catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT REGION 367..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..912
FT /note="B, Ala/Gly-rich"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT REGION 500..698
FT /note="Required for interaction with CyaC"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT REGION 913..1656
FT /note="C"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT REGION 1657..1706
FT /note="D, Asp/Gly-rich"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT BINDING 349..356
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT LIPID 860
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT LIPID 983
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P0DKX7"
FT CONFLICT 292
FT /note="A -> R (in Ref. 1; CAA85481)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="G -> R (in Ref. 1; CAA85481)"
FT /evidence="ECO:0000305"
FT CONFLICT 546..547
FT /note="AA -> G (in Ref. 1; CAA85481)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1706 AA; 177056 MW; AF51E8270EA8A68F CRC64;
MQQSHQAGYA NAADRESGIP AAVLDGIKAV AKEKNATLMF RLVNPHSTSL IAEGVATKGL
GVHAKSSDWG LQAGYIPVNP NLSKLFGRAP EVIARADNDV NSSLAHGHTA VDLTLSKERL
DYLRQAGLVT GMADGVVASN HAGYEQFEFR VKETSDGRYA VQYRRKGGDD FEAVKVIGNA
AGIPLTADID MFAIMPHLSN FRDSARSSVT SGDSVTDYLA RTRRAASEAT GGLDRERIDL
LWKIARAGAR SAVGTEARRQ FRYDGDMNIG VITDFELEVR NALNRRAHAV GAQDVVQHGT
EQNNPFPEAD EKIFVVSATG ESQMLTRGQL KEYIGQQRGE GYVFYENRAY GVAGKSLFDD
GLGAAPGVPG GRSKSSPDVL ETVPASPGLR RPSLGAVERQ DSGYDSLDGV GSRSFSLGEV
SDMAAVEAAE LEMTRQVLHA GARQDDAEPG VSGASAHWGQ RALQGAQAVA AAQRLVHAIA
LMTQFGRAGS TNTPQEAASL SAAVFGLGEA SSAVAETVSG FFRGSSRWAG GFGVAGGAMA
LGGGIAAAVG AGMSLTDDAP AGQKAAAGAE IALQLTGGTV ELASSIALAL AAARGVTSGL
QVAGASAGAA AGALAAALSP MEIYGLVQQS HYADQLDKLA QESSAYGYEG DALLAQLYRD
KTAAEGAVAG VSAVLSTVGA AVSIAAAASV VGAPVAVVTS LLTGALNGIL RGVQQPIIEK
LANDYARKID ELGGPQAYFE KNLQARHEQL ANSDGLRKML ADLQAGWNAS SVIGVQTTEI
SKSALELAAI TGNADNLKSA DVFVDRFIQG ERVAGQPVVL DVAAGGIDIA SRKGERPALT
FITPLAAPGE EQRRRTKTGK SEFTTFVEIV GKQDRWRIRD GAADTTIDLA KVVSQLVDAN
GVLKHSIKLE VIGGDGDDVV LANASRIHYD GGAGTNTVSY AALGRQDSIT VSADGERFNV
RKQLNNANVY REGVATQKTA YGKRTENVQY RHVELARVGQ LVEVDTLEHV QHIIGGAGND
SITGNAHDNF LAGGAGDDRL DGGAGNDTLV GGEGHNTVVG GAGDDVFLQD LGVWSNQLDG
GAGVDTVKYN VHQPSEERLE RMGDTGIHAD LQKGTVEKWP ALNLFSVDHV KNIENLHGSS
LNDSIAGDDR DNELWGDDGN DTIHGRGGDD ILRGGLGLDT LYGEDGNDIF LQDDETVSDD
IDGGAGLDTV DYSAMIHAGK IVAPHEYGFG IEADLSEGWV RKAARRGMDY YDSVRSVENV
IGTSMKDVLI GDAQANTLMG QGGDDTVRGG DGDDLLFGGD GNDMLYGDAG NDTLYGGLGD
DTLEGGAGND WFGQTPAREH DVLRGGAGVD TVDYSQAGAH AGVATGRIGL GILADLGAGR
VDKLGEAGSS AYDTVSGIEN VVGTELADRI TGDAQANVLR GAGGADVLAG GEGDDVLLGG
DGDDQLSGDA GRDRLYGEAG DDWFFQDAAN AGNLLDGGDG NDTVDFSGPG RGLDAGAKGV
FLSLGKGFAS LMDEPETSNV LRHIENAVGS VRDDVLIGDA GANVLNGLAG NDVLSGGAGD
DVLLGDEGSD LLSGDAGNDD LFGGQGDDTY LFGAGYGHDT IYESGGGHDT IRINAGADQL
WFARQGNDLE IRILGTDDAL TVHDWYRDAD HRVEAIHAAN QAIDPAGIEK LVEAMAQYPD
PGAAAAAPPA ARVPDTLMQS LAVNWR
