CYAA_BORP1
ID CYAA_BORP1 Reviewed; 1706 AA.
AC J7QLC0; P15318;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 2.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Bifunctional hemolysin/adenylate cyclase;
DE AltName: Full=AC-HLY;
DE AltName: Full=ACT;
DE AltName: Full=Cyclolysin {ECO:0000303|PubMed:2905265};
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=BN118_0468;
OS Bordetella pertussis (strain ATCC 9797 / DSM 5571 / NCTC 10739 / 18323).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Alcaligenaceae; Bordetella.
OX NCBI_TaxID=568706;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=2897067; DOI=10.1111/j.1365-2958.1988.tb00003.x;
RA Glaser P., Ladant D., Sezer O., Pichot F., Ullmann A., Danchin A.;
RT "The calmodulin-sensitive adenylate cyclase of Bordetella pertussis:
RT cloning and expression in Escherichia coli.";
RL Mol. Microbiol. 2:19-30(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=23051057; DOI=10.1186/1471-2164-13-545;
RA Park J., Zhang Y., Buboltz A.M., Zhang X., Schuster S.C., Ahuja U., Liu M.,
RA Miller J.F., Sebaihia M., Bentley S.D., Parkhill J., Harvill E.T.;
RT "Comparative genomics of the classical Bordetella subspecies: the evolution
RT and exchange of virulence-associated diversity amongst closely related
RT pathogens.";
RL BMC Genomics 13:545-545(2012).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1489-1706, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=2905265; DOI=10.1002/j.1460-2075.1988.tb03288.x;
RA Glaser P., Sakamoto H., Bellalou J., Ullmann A., Danchin A.;
RT "Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-
RT haemolysin bifunctional protein of Bordetella pertussis.";
RL EMBO J. 7:3997-4004(1988).
RN [4]
RP FUNCTION (CALMODULIN-SENSITIVE ADENYLATE CYCLASE).
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=8406793; DOI=10.1128/iai.61.10.4064-4071.1993;
RA Khelef N., Zychlinsky A., Guiso N.;
RT "Bordetella pertussis induces apoptosis in macrophages: role of adenylate
RT cyclase-hemolysin.";
RL Infect. Immun. 61:4064-4071(1993).
RN [5]
RP FUNCTION (HEMOLYSIN), AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=7525549; DOI=10.1016/s0021-9258(18)46973-6;
RA Benz R., Maier E., Ladant D., Ullmann A., Sebo P.;
RT "Adenylate cyclase toxin (CyaA) of Bordetella pertussis. Evidence for the
RT formation of small ion-permeable channels and comparison with HlyA of
RT Escherichia coli.";
RL J. Biol. Chem. 269:27231-27239(1994).
RN [6]
RP FUNCTION (CALMODULIN-SENSITIVE ADENYLATE CYCLASE).
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=9529102; DOI=10.1128/iai.66.4.1718-1725.1998;
RA Gueirard P., Druilhe A., Pretolani M., Guiso N.;
RT "Role of adenylate cyclase-hemolysin in alveolar macrophage apoptosis
RT during Bordetella pertussis infection in vivo.";
RL Infect. Immun. 66:1718-1725(1998).
RN [7]
RP PALMITOYLATION AT LYS-860 AND LYS-983.
RC STRAIN=ATCC 9797 / DSM 5571 / NCTC 10739 / 18323;
RX PubMed=11031260; DOI=10.1074/jbc.m006463200;
RA Basar T., Havlicek V., Bezouskova S., Hackett M., Sebo P.;
RT "Acylation of lysine 983 is sufficient for toxin activity of Bordetella
RT pertussis adenylate cyclase. Substitutions of alanine 140 modulate
RT acylation site selectivity of the toxin acyltransferase CyaC.";
RL J. Biol. Chem. 276:348-354(2001).
CC -!- FUNCTION: Bifunctional adenylate cyclase toxin-hemolysin that plays a
CC crucial role in host colonization (PubMed:2905265). It causes whooping
CC cough by acting on mammalian cells by elevating cAMP-concentration and
CC thus disrupts normal cell function (PubMed:2905265).
CC {ECO:0000269|PubMed:2905265}.
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:0000269|PubMed:2905265, ECO:0000269|PubMed:8406793,
CC ECO:0000269|PubMed:9529102}.
CC -!- FUNCTION: [Hemolysin]: Hemolysin that forms small cation-selective
CC membrane channels, leading to hemolytic activity (PubMed:7525549). The
CC hemolytic activity of CyaA is weak compared with that of the HlyA of
CC E.coli (PubMed:7525549). {ECO:0000269|PubMed:7525549}.
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2905265}.
CC -!- SUBCELLULAR LOCATION: [Hemolysin]: Host cell membrane
CC {ECO:0000305|PubMed:7525549}; Multi-pass membrane protein
CC {ECO:0000305}.
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
CC (PubMed:11031260). The toxin only becomes active when modified in
CC position Lys-983 (PubMed:11031260). Palmitoylation Lys-983 is required
CC for efficient membrane insertion and pore formation of the acylated
CC Hemolysin chain (By similarity). {ECO:0000250|UniProtKB:P0DKX7,
CC ECO:0000269|PubMed:11031260}.
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=CCJ61893.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Y00545; CAA68613.1; -; Genomic_DNA.
DR EMBL; HE965805; CCJ61893.1; ALT_INIT; Genomic_DNA.
DR EMBL; X14199; CAA32411.1; -; Genomic_DNA.
DR PIR; S00893; OYBRC.
DR RefSeq; WP_010929995.1; NC_018518.1.
DR PDB; 5CVW; X-ray; 1.25 A; A=1529-1681.
DR PDB; 6RFM; NMR; -; A=411-490.
DR PDBsum; 5CVW; -.
DR PDBsum; 6RFM; -.
DR AlphaFoldDB; J7QLC0; -.
DR BMRB; J7QLC0; -.
DR SMR; J7QLC0; -.
DR STRING; 568706.BN118_0468; -.
DR PRIDE; J7QLC0; -.
DR EnsemblBacteria; CCJ61893; CCJ61893; BN118_0468.
DR GeneID; 45387797; -.
DR KEGG; bper:BN118_0468; -.
DR eggNOG; COG2931; Bacteria.
DR HOGENOM; CLU_239696_0_0_4; -.
DR Proteomes; UP000005250; 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:0015267; F:channel activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0044179; P:hemolysis in another organism; IDA:UniProtKB.
DR DisProt; DP00591; -.
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; 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; 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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Calcium; Calmodulin-binding; cAMP biosynthesis;
KW Cytolysis; Hemolysis; Host cell membrane; Host membrane; Lipoprotein;
KW Lyase; Membrane; Myristate; Nucleotide-binding; Palmitate; Repeat;
KW Secreted; Toxin; Transmembrane; Virulence; Whooping cough.
FT CHAIN 1..312
FT /note="Calmodulin-sensitive adenylate cyclase"
FT /id="PRO_0000421303"
FT CHAIN 313..1706
FT /note="Hemolysin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000421304"
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 383..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:0000269|PubMed:11031260"
FT LIPID 983
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000269|PubMed:11031260"
FT CONFLICT 1001
FT /note="L -> V (in Ref. 1; CAA68613)"
FT /evidence="ECO:0000305"
FT STRAND 1535..1537
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1544..1546
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1553..1555
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1562..1564
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1571..1573
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1580..1582
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1589..1593
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1598..1601
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1610..1615
FT /evidence="ECO:0007829|PDB:5CVW"
FT HELIX 1617..1619
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1620..1625
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1628..1633
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1639..1642
FT /evidence="ECO:0007829|PDB:5CVW"
FT TURN 1643..1647
FT /evidence="ECO:0007829|PDB:5CVW"
FT HELIX 1649..1651
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1655..1657
FT /evidence="ECO:0007829|PDB:5CVW"
FT STRAND 1662..1664
FT /evidence="ECO:0007829|PDB:5CVW"
FT HELIX 1665..1676
FT /evidence="ECO:0007829|PDB:5CVW"
SQ SEQUENCE 1706 AA; 177521 MW; C1FD3D46CABCEF39 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
GLGAAPGVPS GRSKFSPDVL 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 TGNADNLKSV DVFVDRFVQG ERVAGQPVVL DVAAGGIDIA SRKGERPALT
FITPLAAPGE EQRRRTKTGK SEFTTFVEIV GKQDRWRIRD GAADTTIDLA KVVSQLVDAN
GVLKHSIKLD VIGGDGDDVV LANASRIHYD GGAGTNTVSY AALGRQDSIT VSADGERFNV
RKQLNNANVY REGVATQTTA YGKRTENVQY RHVELARVGQ LVEVDTLEHV QHIIGGAGND
SITGNAHDNF LAGGSGDDRL DGGAGNDTLV GGEGQNTVIG GAGDDVFLQD LGVWSNQLDG
GAGVDTVKYN VHQPSEERLE RMGDTGIHAD LQKGTVEKWP ALNLFSVDHV KNIENLHGSR
LNDRIAGDDQ DNELWGHDGN DTIRGRGGDD ILRGGLGLDT LYGEDGNDIF LQDDETVSDD
IDGGAGLDTV DYSAMIHPGR IVAPHEYGFG IEADLSREWV RKASALGVDY YDNVRNVENV
IGTSMKDVLI GDAQANTLMG QGGDDTVRGG DGDDLLFGGD GNDMLYGDAG NDTLYGGLGD
DTLEGGAGND WFGQTQAREH DVLRGGDGVD TVDYSQTGAH AGIAAGRIGL GILADLGAGR
VDKLGEAGSS AYDTVSGIEN VVGTELADRI TGDAQANVLR GAGGADVLAG GEGDDVLLGG
DGDDQLSGDA GRDRLYGEAG DDWFFQDAAN AGNLLDGGDG RDTVDFSGPG RGLDAGAKGV
FLSLGKGFAS LMDEPETSNV LRNIENAVGS ARDDVLIGDA GANVLNGLAG NDVLSGGAGD
DVLLGDEGSD LLSGDAGNDD LFGGQGDDTY LFGVGYGHDT IYESGGGHDT IRINAGADQL
WFARQGNDLE IRILGTDDAL TVHDWYRDAD HRVEIIHAAN QAVDQAGIEK LVEAMAQYPD
PGAAAAAPPA ARVPDTLMQS LAVNWR
