Bifunctional hemolysin/adenylate cyclase precursor

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P15318 (CYAA_BORPE) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 115. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Bifunctional hemolysin/adenylate cyclase

Alternative name(s):
AC-HLY
ACT
Cyclolysin

Cleaved into the following 2 chains:

Calmodulin-sensitive adenylate cyclase
EC=4.6.1.1
Alternative name(s):
ATP pyrophosphate-lyase
Adenylyl cyclase
Hemolysin

Gene names

Name:	cya
Synonyms:	cyaA
Ordered Locus Names:	BP0760

Organism

Bordetella pertussis

Taxonomic identifier

520 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Betaproteobacteria › Burkholderiales › Alcaligenaceae › Bordetella

Protein attributes

Sequence length	1706 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	This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function. Ref.3
Catalytic activity	ATP = 3',5'-cyclic AMP + diphosphate.
Enzyme regulation	Activated by host calmodulin.
Subcellular location	Secreted.
Domain	The Gly-rich region is probably involved in binding calcium, which is required for target cell-binding or cytolytic activity By similarity. Ref.4
Post-translational modification	Released in a processed form. Palmitoylated by CyaC. The toxin only becomes active when modified in position Lys-983. Ref.8 Ref.9
Sequence similarities	In the N-terminal section; belongs to the adenylyl cyclase class-2 family. In the C-terminal section; belongs to the RTX prokaryotic toxin family. Contains 17 hemolysin-type calcium-binding repeats.

Ontologies

Keywords
Biological process	Cytolysis Hemolysis Virulence cAMP biosynthesis
Cellular component	Secreted
Disease	Whooping cough
Domain	Repeat
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Lyase Toxin
PTM	Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cytolysis Inferred from electronic annotation. Source: UniProtKB-KW hemolysis in other organism Inferred from electronic annotation. Source: UniProtKB-KW pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro calcium- and calmodulin-responsive adenylate cyclase activity Inferred from electronic annotation. Source: InterPro calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 312

312

Calmodulin-sensitive adenylate cyclase

PRO_0000001320

Chain

313 – 1706

1394

Hemolysin Potential

PRO_0000001321

Regions

Repeat

1014 – 1031

Hemolysin-type calcium-binding 1

Repeat

1032 – 1049

Hemolysin-type calcium-binding 2

Repeat

1050 – 1067

Hemolysin-type calcium-binding 3

Repeat

1155 – 1172

Hemolysin-type calcium-binding 4

Repeat

1173 – 1190

Hemolysin-type calcium-binding 5

Repeat

1279 – 1296

Hemolysin-type calcium-binding 6

Repeat

1297 – 1314

Hemolysin-type calcium-binding 7

Repeat

1315 – 1332

Hemolysin-type calcium-binding 8

Repeat

1335 – 1352

Hemolysin-type calcium-binding 9

Repeat

1411 – 1428

Hemolysin-type calcium-binding 10

Repeat

1429 – 1446

Hemolysin-type calcium-binding 11

Repeat

1447 – 1464

Hemolysin-type calcium-binding 12

Repeat

1468 – 1484

Hemolysin-type calcium-binding 13

Repeat

1537 – 1554

Hemolysin-type calcium-binding 14

Repeat

1555 – 1572

Hemolysin-type calcium-binding 15

Repeat

1573 – 1590

Hemolysin-type calcium-binding 16

Repeat

1603 – 1620

Hemolysin-type calcium-binding 17

Nucleotide binding

349 – 356

ATP Potential

Region

1 – 399

399

A, catalytic

Region

400 – 912

513

B, Ala/Gly-rich

Region

913 – 1656

744

Region

1657 – 1706

D, Asp/Gly-rich

Amino acid modifications

Lipidation

860

N6-palmitoyl lysine Ref.9

Lipidation

983

N6-palmitoyl lysine Ref.8

Experimental info

Mutagenesis

188

D → E, N, Y or H: Loss of activity.

Mutagenesis

190

D → N, Y or H: Loss of activity.

Mutagenesis

298

H → R, P or L: Loss of activity.

Mutagenesis

301

E → Q or K: Loss of activity.

Sequence conflict

1001

L → V in CAA68613. Ref.1

Secondary structure

1706

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P15318 [UniParc].

Last modified September 19, 2003. Version 2.
Checksum: C1FD3D46CABCEF39
Show »

FASTA

1,706

177,521

        10         20         30         40         50         60 
MQQSHQAGYA NAADRESGIP AAVLDGIKAV AKEKNATLMF RLVNPHSTSL IAEGVATKGL 

        70         80         90        100        110        120 
GVHAKSSDWG LQAGYIPVNP NLSKLFGRAP EVIARADNDV NSSLAHGHTA VDLTLSKERL 

       130        140        150        160        170        180 
DYLRQAGLVT GMADGVVASN HAGYEQFEFR VKETSDGRYA VQYRRKGGDD FEAVKVIGNA 

       190        200        210        220        230        240 
AGIPLTADID MFAIMPHLSN FRDSARSSVT SGDSVTDYLA RTRRAASEAT GGLDRERIDL 

       250        260        270        280        290        300 
LWKIARAGAR SAVGTEARRQ FRYDGDMNIG VITDFELEVR NALNRRAHAV GAQDVVQHGT 

       310        320        330        340        350        360 
EQNNPFPEAD EKIFVVSATG ESQMLTRGQL KEYIGQQRGE GYVFYENRAY GVAGKSLFDD 

       370        380        390        400        410        420 
GLGAAPGVPS GRSKFSPDVL ETVPASPGLR RPSLGAVERQ DSGYDSLDGV GSRSFSLGEV 

       430        440        450        460        470        480 
SDMAAVEAAE LEMTRQVLHA GARQDDAEPG VSGASAHWGQ RALQGAQAVA AAQRLVHAIA 

       490        500        510        520        530        540 
LMTQFGRAGS TNTPQEAASL SAAVFGLGEA SSAVAETVSG FFRGSSRWAG GFGVAGGAMA 

       550        560        570        580        590        600 
LGGGIAAAVG AGMSLTDDAP AGQKAAAGAE IALQLTGGTV ELASSIALAL AAARGVTSGL 

       610        620        630        640        650        660 
QVAGASAGAA AGALAAALSP MEIYGLVQQS HYADQLDKLA QESSAYGYEG DALLAQLYRD 

       670        680        690        700        710        720 
KTAAEGAVAG VSAVLSTVGA AVSIAAAASV VGAPVAVVTS LLTGALNGIL RGVQQPIIEK 

       730        740        750        760        770        780 
LANDYARKID ELGGPQAYFE KNLQARHEQL ANSDGLRKML ADLQAGWNAS SVIGVQTTEI 

       790        800        810        820        830        840 
SKSALELAAI TGNADNLKSV DVFVDRFVQG ERVAGQPVVL DVAAGGIDIA SRKGERPALT 

       850        860        870        880        890        900 
FITPLAAPGE EQRRRTKTGK SEFTTFVEIV GKQDRWRIRD GAADTTIDLA KVVSQLVDAN 

       910        920        930        940        950        960 
GVLKHSIKLD VIGGDGDDVV LANASRIHYD GGAGTNTVSY AALGRQDSIT VSADGERFNV 

       970        980        990       1000       1010       1020 
RKQLNNANVY REGVATQTTA YGKRTENVQY RHVELARVGQ LVEVDTLEHV QHIIGGAGND 

      1030       1040       1050       1060       1070       1080 
SITGNAHDNF LAGGSGDDRL DGGAGNDTLV GGEGQNTVIG GAGDDVFLQD LGVWSNQLDG 

      1090       1100       1110       1120       1130       1140 
GAGVDTVKYN VHQPSEERLE RMGDTGIHAD LQKGTVEKWP ALNLFSVDHV KNIENLHGSR 

      1150       1160       1170       1180       1190       1200 
LNDRIAGDDQ DNELWGHDGN DTIRGRGGDD ILRGGLGLDT LYGEDGNDIF LQDDETVSDD 

      1210       1220       1230       1240       1250       1260 
IDGGAGLDTV DYSAMIHPGR IVAPHEYGFG IEADLSREWV RKASALGVDY YDNVRNVENV 

      1270       1280       1290       1300       1310       1320 
IGTSMKDVLI GDAQANTLMG QGGDDTVRGG DGDDLLFGGD GNDMLYGDAG NDTLYGGLGD 

      1330       1340       1350       1360       1370       1380 
DTLEGGAGND WFGQTQAREH DVLRGGDGVD TVDYSQTGAH AGIAAGRIGL GILADLGAGR 

      1390       1400       1410       1420       1430       1440 
VDKLGEAGSS AYDTVSGIEN VVGTELADRI TGDAQANVLR GAGGADVLAG GEGDDVLLGG 

      1450       1460       1470       1480       1490       1500 
DGDDQLSGDA GRDRLYGEAG DDWFFQDAAN AGNLLDGGDG RDTVDFSGPG RGLDAGAKGV 

      1510       1520       1530       1540       1550       1560 
FLSLGKGFAS LMDEPETSNV LRNIENAVGS ARDDVLIGDA GANVLNGLAG NDVLSGGAGD 

      1570       1580       1590       1600       1610       1620 
DVLLGDEGSD LLSGDAGNDD LFGGQGDDTY LFGVGYGHDT IYESGGGHDT IRINAGADQL 

      1630       1640       1650       1660       1670       1680 
WFARQGNDLE IRILGTDDAL TVHDWYRDAD HRVEIIHAAN QAVDQAGIEK LVEAMAQYPD 

      1690       1700 
PGAAAAAPPA ARVPDTLMQS LAVNWR

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli." Glaser P., Ladant D., Sezer O., Pichot F., Ullmann A., Danchin A. Mol. Microbiol. 2:19-30(1988) [PubMed: 2897067] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 18323.
[2]	"Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica." Parkhill J., Sebaihia M., Preston A., Murphy L.D., Thomson N.R., Harris D.E., Holden M.T.G., Churcher C.M., Bentley S.D., Mungall K.L., Cerdeno-Tarraga A.-M., Temple L., James K.D., Harris B., Quail M.A., Achtman M., Atkin R., Baker S. Maskell D.J. Nat. Genet. 35:32-40(2003) [PubMed: 12910271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Tohama I / ATCC BAA-589 / NCTC 13251.
[3]	"Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis." Glaser P., Sakamoto H., Bellalou J., Ullmann A., Danchin A. EMBO J. 7:3997-4004(1988) [PubMed: 2905265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1489-1706, FUNCTION. Strain: 18323.
[4]	"Isolation and characterization of catalytic and calmodulin-binding domains of Bordetella pertussis adenylate cyclase." Munier H., Gilles A.-M., Glaser P., Danchin A., Sarfati R., Barzu O. Eur. J. Biochem. 196:469-474(1991) [PubMed: 2007407] [Abstract] Cited for: DOMAINS.
[5]	"Identification of residues essential for catalysis and binding of calmodulin in Bordetella pertussis adenylate cyclase by site-directed mutagenesis." Glaser P., Elmaoglou-Lazaridou A., Krin E., Ladant D., Barzu O., Danchin A. EMBO J. 8:967-972(1989) [PubMed: 2542030] [Abstract] Cited for: MUTAGENESIS.
[6]	"Functional consequences of single amino acid substitutions in calmodulin-activated adenylate cyclase of Bordetella pertussis." Glaser P., Munier H., Gilles A.-M., Krin E., Porumb T., Barzu O., Sarfati R., Pellecuer C., Danchin A. EMBO J. 10:1683-1688(1991) [PubMed: 2050107] [Abstract] Cited for: MUTAGENESIS.
[7]	"Phylogeny of adenylyl cyclases." Danchin A. Adv. Second Messenger Phosphoprotein Res. 27:109-162(1993) [PubMed: 8418825] [Abstract] Cited for: REVIEW.
[8]	"Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis." Hackett M., Guo L., Shabanowitz J., Hunt D.F., Hewlett E.L. Science 266:433-435(1994) [PubMed: 7939682] [Abstract] Cited for: PALMITOYLATION AT LYS-983.
[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., Havlicek V., Bezouskova S., Halada P., Hackett M., Sebo P. J. Biol. Chem. 274:10777-10783(1999) [PubMed: 10196151] [Abstract] Cited for: PALMITOYLATION AT LYS-860.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00545 Genomic DNA. Translation: CAA68613.1.
BX640413 Genomic DNA. Translation: CAE41066.1.
X14199 Genomic DNA. Translation: CAA32411.1.

PIR

OYBRC. S00893.

RefSeq

NP_879578.1. NC_002929.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YRT	X-ray	2.10	A	1-364	[»]
1YRU	X-ray	2.50	A	1-364	[»]
1ZOT	X-ray	2.20	A	7-364	[»]
2COL	X-ray	2.20	A	7-362	[»]

ProteinModelPortal

P15318.

SMR

P15318. Positions 7-364.

ModBase

Search...

Protein family/group databases

TCDB

1.C.11.1.4. pore-forming RTX toxin (RTX-toxin) family.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

2664492.

GenomeReviews

Gene locus BP0760 in contig BX470248_GR.

KEGG

bpe:BP0760.

NMPDR

fig|257313.1.peg.657.

PATRIC

21154616. VBIBorPer7866_0813.

Phylogenomic databases

HOGENOM

HBG353287.

OMA

NDRIAGD.

ProtClustDB

CLSK265825.

Enzyme and pathway databases

BioCyc

BPER257313:BP0760-MONOMER.

Family and domain databases

InterPro

IPR005165. Anthrax_toxin_edema_cen.
IPR018511. Hemolysin-typ_Ca-bd_CS.
IPR001343. Hemolysn_Ca-bd.
IPR018504. RTX_N.
IPR003995. RTX_toxin_determinant-A.
IPR011049. Serralysin-like_metalloprot_C.
[Graphical view]

K11005.
K11029.

Pfam

PF03497. Anthrax_toxA. 1 hit.
PF00353. HemolysinCabind. 17 hits.
PF02382. RTX. 1 hit.
[Graphical view]

PRINTS

PR01488. RTXTOXINA.

SUPFAM

SSF51120. Serralysn_like_C. 5 hits.

PROSITE

PS00330. HEMOLYSIN_CALCIUM. 5 hits.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CYAA_BORPE

Accession

Primary (citable) accession number: P15318

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	September 19, 2003
Last modified:	January 25, 2012
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

Protocols and materials databases

Genome annotation databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents