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Protein

Bifunctional hemolysin/adenylate cyclase

Gene

cya

Organism
Bordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.

Enzyme regulationi

Activated by host calmodulin.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi349 – 3568ATPSequence analysis

GO - Molecular functioni

GO - Biological processi

  • hemolysis in other organism Source: CACAO
  • pathogenesis Source: UniProtKB-KW
  • positive regulation of cytosolic calcium ion concentration Source: CACAO
Complete GO annotation...

Keywords - Molecular functioni

Lyase, Toxin

Keywords - Biological processi

cAMP biosynthesis, Cytolysis, Hemolysis, Virulence

Keywords - Ligandi

ATP-binding, Calcium, Calmodulin-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional hemolysin/adenylate cyclase
Alternative name(s):
AC-HLY
ACT
Cyclolysin
Cleaved into the following 2 chains:
Alternative name(s):
ATP pyrophosphate-lyase
Adenylyl cyclase
Gene namesi
Name:cya
Synonyms:cyaA
Ordered Locus Names:BP0760
OrganismiBordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251)
Taxonomic identifieri257313 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaBetaproteobacteriaBurkholderialesAlcaligenaceaeBordetella
Proteomesi
  • UP000002676 Componenti: Chromosome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi188 – 1881D → E, N, Y or H: Loss of activity.
Mutagenesisi190 – 1901D → N, Y or H: Loss of activity.
Mutagenesisi298 – 2981H → R, P or L: Loss of activity.
Mutagenesisi301 – 3011E → Q or K: Loss of activity.

Keywords - Diseasei

Whooping cough

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 312312Calmodulin-sensitive adenylate cyclasePRO_0000001320Add
BLAST
Chaini313 – 17061394HemolysinSequence analysisPRO_0000001321Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi860 – 8601N6-palmitoyl lysine1 Publication
Lipidationi983 – 9831N6-palmitoyl lysine1 Publication

Post-translational modificationi

Released in a processed form.
Palmitoylated by CyaC. The toxin only becomes active when modified in position Lys-983.2 Publications

Keywords - PTMi

Lipoprotein, Palmitate

Interactioni

Protein-protein interaction databases

STRINGi257313.BP0760.

Structurei

Secondary structure

1
1706
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi12 – 165Combined sources
Helixi21 – 3313Combined sources
Beta strandi36 – 416Combined sources
Helixi45 – 528Combined sources
Helixi70 – 723Combined sources
Beta strandi77 – 793Combined sources
Helixi80 – 823Combined sources
Turni84 – 874Combined sources
Helixi90 – 10516Combined sources
Beta strandi109 – 1124Combined sources
Helixi117 – 1259Combined sources
Beta strandi131 – 1388Combined sources
Helixi142 – 1454Combined sources
Beta strandi147 – 1537Combined sources
Beta strandi159 – 1657Combined sources
Beta strandi168 – 1736Combined sources
Beta strandi175 – 1784Combined sources
Beta strandi184 – 1863Combined sources
Beta strandi191 – 1977Combined sources
Helixi198 – 2014Combined sources
Helixi202 – 2098Combined sources
Beta strandi210 – 2123Combined sources
Helixi215 – 2228Combined sources
Helixi235 – 25218Combined sources
Turni253 – 2564Combined sources
Helixi257 – 2593Combined sources
Beta strandi262 – 2643Combined sources
Beta strandi267 – 2715Combined sources
Helixi274 – 28916Combined sources
Helixi301 – 3033Combined sources
Beta strandi313 – 3164Combined sources
Beta strandi322 – 3254Combined sources
Helixi327 – 33913Combined sources
Turni348 – 3547Combined sources
Beta strandi1535 – 15373Combined sources
Beta strandi1544 – 15463Combined sources
Beta strandi1553 – 15553Combined sources
Beta strandi1562 – 15643Combined sources
Beta strandi1571 – 15733Combined sources
Beta strandi1580 – 15823Combined sources
Beta strandi1589 – 15935Combined sources
Beta strandi1598 – 16014Combined sources
Beta strandi1610 – 16156Combined sources
Helixi1617 – 16193Combined sources
Beta strandi1620 – 16256Combined sources
Beta strandi1628 – 16336Combined sources
Beta strandi1639 – 16424Combined sources
Turni1643 – 16475Combined sources
Helixi1649 – 16513Combined sources
Beta strandi1654 – 16585Combined sources
Beta strandi1661 – 16644Combined sources
Helixi1665 – 167410Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YRTX-ray2.10A1-364[»]
1YRUX-ray2.50A1-364[»]
1ZOTX-ray2.20A7-364[»]
2COLX-ray2.20A7-362[»]
5CXLX-ray1.45A/B1529-1681[»]
DisProtiDP00591.
ProteinModelPortaliP0DKX7.
SMRiP0DKX7. Positions 7-364.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati1014 – 103118Hemolysin-type calcium-binding 1Add
BLAST
Repeati1032 – 104918Hemolysin-type calcium-binding 2Add
BLAST
Repeati1050 – 106718Hemolysin-type calcium-binding 3Add
BLAST
Repeati1155 – 117218Hemolysin-type calcium-binding 4Add
BLAST
Repeati1173 – 119018Hemolysin-type calcium-binding 5Add
BLAST
Repeati1279 – 129618Hemolysin-type calcium-binding 6Add
BLAST
Repeati1297 – 131418Hemolysin-type calcium-binding 7Add
BLAST
Repeati1315 – 133218Hemolysin-type calcium-binding 8Add
BLAST
Repeati1335 – 135218Hemolysin-type calcium-binding 9Add
BLAST
Repeati1411 – 142818Hemolysin-type calcium-binding 10Add
BLAST
Repeati1429 – 144618Hemolysin-type calcium-binding 11Add
BLAST
Repeati1447 – 146418Hemolysin-type calcium-binding 12Add
BLAST
Repeati1468 – 148417Hemolysin-type calcium-binding 13Add
BLAST
Repeati1537 – 155418Hemolysin-type calcium-binding 14Add
BLAST
Repeati1555 – 157218Hemolysin-type calcium-binding 15Add
BLAST
Repeati1573 – 159018Hemolysin-type calcium-binding 16Add
BLAST
Repeati1603 – 162018Hemolysin-type calcium-binding 17Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 399399A, catalyticAdd
BLAST
Regioni400 – 912513B, Ala/Gly-richAdd
BLAST
Regioni913 – 1656744CAdd
BLAST
Regioni1657 – 170650D, Asp/Gly-richAdd
BLAST

Domaini

The Gly-rich region is probably involved in binding calcium, which is required for target cell-binding or cytolytic activity.By similarity

Sequence similaritiesi

In the N-terminal section; belongs to the adenylyl cyclase class-2 family.Curated
In the C-terminal section; belongs to the RTX prokaryotic toxin family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG4107VZP. Bacteria.
COG2931. LUCA.
KOiK11005.
K11029.
OMAiPGDNGLR.

Family and domain databases

Gene3Di2.150.10.10. 6 hits.
InterProiIPR005165. 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]
PfamiPF03497. Anthrax_toxA. 1 hit.
PF00353. HemolysinCabind. 15 hits.
PF02382. RTX. 1 hit.
[Graphical view]
PRINTSiPR01488. RTXTOXINA.
SUPFAMiSSF51120. SSF51120. 9 hits.
PROSITEiPS00330. HEMOLYSIN_CALCIUM. 5 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P0DKX7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQQSHQAGYA NAADRESGIP AAVLDGIKAV AKEKNATLMF RLVNPHSTSL
60 70 80 90 100
IAEGVATKGL GVHAKSSDWG LQAGYIPVNP NLSKLFGRAP EVIARADNDV
110 120 130 140 150
NSSLAHGHTA VDLTLSKERL DYLRQAGLVT GMADGVVASN HAGYEQFEFR
160 170 180 190 200
VKETSDGRYA VQYRRKGGDD FEAVKVIGNA AGIPLTADID MFAIMPHLSN
210 220 230 240 250
FRDSARSSVT SGDSVTDYLA RTRRAASEAT GGLDRERIDL LWKIARAGAR
260 270 280 290 300
SAVGTEARRQ FRYDGDMNIG VITDFELEVR NALNRRAHAV GAQDVVQHGT
310 320 330 340 350
EQNNPFPEAD EKIFVVSATG ESQMLTRGQL KEYIGQQRGE GYVFYENRAY
360 370 380 390 400
GVAGKSLFDD GLGAAPGVPS GRSKFSPDVL ETVPASPGLR RPSLGAVERQ
410 420 430 440 450
DSGYDSLDGV GSRSFSLGEV SDMAAVEAAE LEMTRQVLHA GARQDDAEPG
460 470 480 490 500
VSGASAHWGQ RALQGAQAVA AAQRLVHAIA LMTQFGRAGS TNTPQEAASL
510 520 530 540 550
SAAVFGLGEA SSAVAETVSG FFRGSSRWAG GFGVAGGAMA LGGGIAAAVG
560 570 580 590 600
AGMSLTDDAP AGQKAAAGAE IALQLTGGTV ELASSIALAL AAARGVTSGL
610 620 630 640 650
QVAGASAGAA AGALAAALSP MEIYGLVQQS HYADQLDKLA QESSAYGYEG
660 670 680 690 700
DALLAQLYRD KTAAEGAVAG VSAVLSTVGA AVSIAAAASV VGAPVAVVTS
710 720 730 740 750
LLTGALNGIL RGVQQPIIEK LANDYARKID ELGGPQAYFE KNLQARHEQL
760 770 780 790 800
ANSDGLRKML ADLQAGWNAS SVIGVQTTEI SKSALELAAI TGNADNLKSV
810 820 830 840 850
DVFVDRFVQG ERVAGQPVVL DVAAGGIDIA SRKGERPALT FITPLAAPGE
860 870 880 890 900
EQRRRTKTGK SEFTTFVEIV GKQDRWRIRD GAADTTIDLA KVVSQLVDAN
910 920 930 940 950
GVLKHSIKLD VIGGDGDDVV LANASRIHYD GGAGTNTVSY AALGRQDSIT
960 970 980 990 1000
VSADGERFNV RKQLNNANVY REGVATQTTA YGKRTENVQY RHVELARVGQ
1010 1020 1030 1040 1050
LVEVDTLEHV QHIIGGAGND SITGNAHDNF LAGGSGDDRL DGGAGNDTLV
1060 1070 1080 1090 1100
GGEGQNTVIG GAGDDVFLQD LGVWSNQLDG GAGVDTVKYN VHQPSEERLE
1110 1120 1130 1140 1150
RMGDTGIHAD LQKGTVEKWP ALNLFSVDHV KNIENLHGSR LNDRIAGDDQ
1160 1170 1180 1190 1200
DNELWGHDGN DTIRGRGGDD ILRGGLGLDT LYGEDGNDIF LQDDETVSDD
1210 1220 1230 1240 1250
IDGGAGLDTV DYSAMIHPGR IVAPHEYGFG IEADLSREWV RKASALGVDY
1260 1270 1280 1290 1300
YDNVRNVENV IGTSMKDVLI GDAQANTLMG QGGDDTVRGG DGDDLLFGGD
1310 1320 1330 1340 1350
GNDMLYGDAG NDTLYGGLGD DTLEGGAGND WFGQTQAREH DVLRGGDGVD
1360 1370 1380 1390 1400
TVDYSQTGAH AGIAAGRIGL GILADLGAGR VDKLGEAGSS AYDTVSGIEN
1410 1420 1430 1440 1450
VVGTELADRI TGDAQANVLR GAGGADVLAG GEGDDVLLGG DGDDQLSGDA
1460 1470 1480 1490 1500
GRDRLYGEAG DDWFFQDAAN AGNLLDGGDG RDTVDFSGPG RGLDAGAKGV
1510 1520 1530 1540 1550
FLSLGKGFAS LMDEPETSNV LRNIENAVGS ARDDVLIGDA GANVLNGLAG
1560 1570 1580 1590 1600
NDVLSGGAGD DVLLGDEGSD LLSGDAGNDD LFGGQGDDTY LFGVGYGHDT
1610 1620 1630 1640 1650
IYESGGGHDT IRINAGADQL WFARQGNDLE IRILGTDDAL TVHDWYRDAD
1660 1670 1680 1690 1700
HRVEIIHAAN QAVDQAGIEK LVEAMAQYPD PGAAAAAPPA ARVPDTLMQS

LAVNWR
Length:1,706
Mass (Da):177,521
Last modified:March 6, 2013 - v1
Checksum:iC1FD3D46CABCEF39
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX640413 Genomic DNA. Translation: CAE41066.1.
PIRiS00893. OYBRC.
RefSeqiNP_879578.1. NC_002929.2.
WP_010929995.1. NC_002929.2.

Genome annotation databases

EnsemblBacteriaiCAE41066; CAE41066; BP0760.
GeneIDi2664492.
KEGGibpe:BP0760.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX640413 Genomic DNA. Translation: CAE41066.1.
PIRiS00893. OYBRC.
RefSeqiNP_879578.1. NC_002929.2.
WP_010929995.1. NC_002929.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YRTX-ray2.10A1-364[»]
1YRUX-ray2.50A1-364[»]
1ZOTX-ray2.20A7-364[»]
2COLX-ray2.20A7-362[»]
5CXLX-ray1.45A/B1529-1681[»]
DisProtiDP00591.
ProteinModelPortaliP0DKX7.
SMRiP0DKX7. Positions 7-364.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi257313.BP0760.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCAE41066; CAE41066; BP0760.
GeneIDi2664492.
KEGGibpe:BP0760.

Phylogenomic databases

eggNOGiENOG4107VZP. Bacteria.
COG2931. LUCA.
KOiK11005.
K11029.
OMAiPGDNGLR.

Family and domain databases

Gene3Di2.150.10.10. 6 hits.
InterProiIPR005165. 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]
PfamiPF03497. Anthrax_toxA. 1 hit.
PF00353. HemolysinCabind. 15 hits.
PF02382. RTX. 1 hit.
[Graphical view]
PRINTSiPR01488. RTXTOXINA.
SUPFAMiSSF51120. SSF51120. 9 hits.
PROSITEiPS00330. HEMOLYSIN_CALCIUM. 5 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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.
    , Basham D., Bason N., Cherevach I., Chillingworth T., Collins M., Cronin A., Davis P., Doggett J., Feltwell T., Goble A., Hamlin N., Hauser H., Holroyd S., Jagels K., Leather S., Moule S., Norberczak H., O'Neil S., Ormond D., Price C., Rabbinowitsch E., Rutter S., Sanders M., Saunders D., Seeger K., Sharp S., Simmonds M., Skelton J., Squares R., Squares S., Stevens K., Unwin L., Whitehead S., Barrell B.G., Maskell D.J.
    Nat. Genet. 35:32-40(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Tohama I / ATCC BAA-589 / NCTC 13251.
  2. "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] [Europe PMC] [Abstract]
    Cited for: DOMAINS.
  3. "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] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS.
  4. "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] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS.
  5. "Phylogeny of adenylyl cyclases."
    Danchin A.
    Adv. Second Messenger Phosphoprotein Res. 27:109-162(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. "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] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT LYS-983.
  7. "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] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT LYS-860.

Entry informationi

Entry nameiCYAA_BORPE
AccessioniPrimary (citable) accession number: P0DKX7
Secondary accession number(s): P15318
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2013
Last sequence update: March 6, 2013
Last modified: July 6, 2016
This is version 25 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.