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Protein

Calmodulin-sensitive adenylate cyclase

Gene

cya

Organism
Bacillus anthracis
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. EF is a calmodulin-dependent adenylyl cyclase that, when associated with PA, causes edema. EF is not toxic by itself and it is required for the survival of germinated spores within macrophages at the early stages of infection. Provokes dramatic elevation of intracellular cAMP levels in the host.

Catalytic activityi

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

Cofactori

Enzyme regulationi

It has an absolute requirement for host calmodulin for its activation. Inhibited by ethyl 5-aminopyrazolo[1,5-a]quinazoline-3-carboxylate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei351Proton acceptor1
Metal bindingi491Magnesium1
Metal bindingi493Magnesium1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase, Toxin

Keywords - Biological processi

cAMP biosynthesis, Virulence

Keywords - Ligandi

ATP-binding, Calcium, Calmodulin-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciANTHRA:GBAA_PXO1_0142-MONOMER.
ReactomeiR-HSA-5210891. Uptake and function of anthrax toxins.

Names & Taxonomyi

Protein namesi
Recommended name:
Calmodulin-sensitive adenylate cyclase (EC:4.6.1.1)
Alternative name(s):
ATP pyrophosphate-lyase
Adenylyl cyclase
Anthrax edema toxin adenylate cyclase component
Edema factor
Short name:
EF
Gene namesi
Name:cya
Ordered Locus Names:pXO1-122, BXA0141, GBAA_pXO1_0142
Encoded oniPlasmid pXO10 Publication
OrganismiBacillus anthracis
Taxonomic identifieri1392 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesBacillaceaeBacillusBacillus cereus group
Proteomesi
  • UP000000594 Componenti: Plasmid pXO1

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi169V → A: No effect. 1 Publication1
Mutagenesisi170Y → A: Loss of cytotoxicity due to inability to bind PA. 1 Publication1
Mutagenesisi171Y → A: Loss of cytotoxicity due to inability to bind PA. 1 Publication1
Mutagenesisi172E → A: No effect. 1 Publication1
Mutagenesisi173I → A: Loss of cytotoxicity due to inability to bind PA. 1 Publication1
Mutagenesisi174G → A: No effect. 1 Publication1
Mutagenesisi175K → A: Loss of cytotoxicity due to inability to bind PA. 1 Publication1
Mutagenesisi329R → M: Great decrease in activity. 1 Publication1
Mutagenesisi346K → M or R: Loss of activity. 2 Publications1
Mutagenesisi346K → Q: Loss of activity due to inability to bind the substrate. 2 Publications1
Mutagenesisi353K → M, R or A: Loss of activity. 1 Publication1
Mutagenesisi436E → Q: Decreases activity. 1 Publication1
Mutagenesisi443E → Q: Decreases activity. 1 Publication1
Mutagenesisi491D → N: Great decrease in activity. 1 Publication1
Mutagenesisi493D → N: Great decrease in activity. 1 Publication1
Mutagenesisi523L → A: Little effect on activation by calmodulin. 1 Publication1
Mutagenesisi525K → A: Great decrease in calmodulin binding. 1 Publication1
Mutagenesisi526Q → A: Little effect on activation by calmodulin. 1 Publication1
Mutagenesisi529V → A: Little effect on activation by calmodulin. 1 Publication1
Mutagenesisi577H → N or D: Loss of function. 1 Publication1
Mutagenesisi583N → A: Decreases activity. 1 Publication1
Mutagenesisi583N → Q or H: Loss of function. 1 Publication1
Mutagenesisi588E → A: Loss of function. 1 Publication1
Mutagenesisi590D → A: Decreases activity. 1 Publication1
Mutagenesisi639N → A: Decreases catalysis rate. 1 Publication1
Mutagenesisi647D → A: Decreases activity due to reduced activation by calmodulin. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5396.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 331 PublicationAdd BLAST33
ChainiPRO_000000131734 – 800Calmodulin-sensitive adenylate cyclaseAdd BLAST767

Proteomic databases

PRIDEiP40136.

Interactioni

Subunit structurei

Anthrax toxins are composed of three distinct proteins, a protective antigen (PA), a lethal factor (LF) and an edema factor (EF). None of these is toxic by itself. PA+LF forms the lethal toxin (LeTx); PA+EF forms the edema toxin (EdTx). EF probably forms oligomers as part of the translocation machinery, formed by a heterocomplex of PA63 monomers and EF subunits, and it is functional as a monomer in the host cell.

Binary interactionsi

WithEntry#Exp.IntActNotes
calm2P621552EBI-457011,EBI-397568From a different organism.
CALM3P621588EBI-457011,EBI-397435From a different organism.

Protein-protein interaction databases

DIPiDIP-31055N.
IntActiP40136. 3 interactors.

Chemistry databases

BindingDBiP40136.

Structurei

Secondary structure

1800
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi67 – 69Combined sources3
Helixi76 – 86Combined sources11
Helixi91 – 99Combined sources9
Beta strandi103 – 109Combined sources7
Turni111 – 114Combined sources4
Beta strandi119 – 122Combined sources4
Beta strandi130 – 132Combined sources3
Helixi137 – 139Combined sources3
Beta strandi141 – 144Combined sources4
Beta strandi147 – 149Combined sources3
Beta strandi151 – 155Combined sources5
Turni163 – 168Combined sources6
Helixi169 – 176Combined sources8
Turni177 – 182Combined sources6
Beta strandi183 – 188Combined sources6
Helixi192 – 197Combined sources6
Turni198 – 202Combined sources5
Beta strandi203 – 206Combined sources4
Turni211 – 213Combined sources3
Beta strandi215 – 217Combined sources3
Beta strandi226 – 229Combined sources4
Turni230 – 235Combined sources6
Helixi236 – 249Combined sources14
Beta strandi250 – 252Combined sources3
Helixi255 – 259Combined sources5
Beta strandi260 – 262Combined sources3
Helixi263 – 273Combined sources11
Helixi275 – 290Combined sources16
Beta strandi296 – 298Combined sources3
Helixi299 – 305Combined sources7
Helixi309 – 322Combined sources14
Beta strandi324 – 328Combined sources5
Turni333 – 335Combined sources3
Helixi336 – 340Combined sources5
Beta strandi356 – 360Combined sources5
Beta strandi365 – 367Combined sources3
Helixi368 – 370Combined sources3
Turni372 – 375Combined sources4
Helixi377 – 393Combined sources17
Turni394 – 396Combined sources3
Beta strandi397 – 402Combined sources6
Helixi407 – 415Combined sources9
Beta strandi424 – 427Combined sources4
Beta strandi430 – 436Combined sources7
Beta strandi440 – 450Combined sources11
Beta strandi452 – 457Combined sources6
Turni464 – 466Combined sources3
Beta strandi471 – 473Combined sources3
Beta strandi475 – 489Combined sources15
Beta strandi494 – 500Combined sources7
Helixi501 – 507Combined sources7
Helixi510 – 516Combined sources7
Beta strandi517 – 521Combined sources5
Helixi527 – 535Combined sources9
Turni536 – 538Combined sources3
Beta strandi541 – 543Combined sources3
Beta strandi544 – 546Combined sources3
Beta strandi547 – 549Combined sources3
Helixi551 – 565Combined sources15
Turni566 – 568Combined sources3
Helixi580 – 582Combined sources3
Beta strandi593 – 596Combined sources4
Beta strandi598 – 600Combined sources3
Beta strandi602 – 607Combined sources6
Helixi608 – 618Combined sources11
Helixi620 – 622Combined sources3
Turni630 – 633Combined sources4
Beta strandi634 – 636Combined sources3
Turni637 – 639Combined sources3
Turni648 – 650Combined sources3
Turni652 – 655Combined sources4
Helixi660 – 674Combined sources15
Beta strandi679 – 681Combined sources3
Beta strandi683 – 685Combined sources3
Helixi687 – 706Combined sources20
Helixi707 – 710Combined sources4
Helixi714 – 737Combined sources24
Helixi743 – 767Combined sources25
Helixi771 – 777Combined sources7
Beta strandi778 – 780Combined sources3
Helixi786 – 798Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K8TX-ray2.60A291-800[»]
1K90X-ray2.75A/B/C291-800[»]
1K93X-ray2.95A/B/C291-800[»]
1LVCX-ray3.60A/B/C291-800[»]
1PK0X-ray3.30A/B/C292-798[»]
1S26X-ray3.00A/B/C291-800[»]
1SK6X-ray3.20A/B/C291-800[»]
1XFUX-ray3.35A/B/C/D/E/F64-800[»]
1XFVX-ray3.35A/B/C/D/E/F33-800[»]
1XFWX-ray3.40A/B/C/D/E/F33-800[»]
1XFXX-ray3.20A/B/C/D/E/F33-800[»]
1XFYX-ray3.30A/B/C/D/E/F33-800[»]
1XFZX-ray3.25A/B/C/D/E/F33-800[»]
1Y0VX-ray3.60A/B/C/D/E/F33-800[»]
DisProtiDP00395.
ProteinModelPortaliP40136.
SMRiP40136.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40136.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni34 – 290Interaction with protective antigenAdd BLAST257
Regioni294 – 349Catalytic CA1Add BLAST56
Regioni350 – 489Catalytic CBAdd BLAST140
Regioni490 – 622Catalytic CA2Add BLAST133
Regioni623 – 800Interaction with calmodulinAdd BLAST178

Domaini

The N-terminal region contains the residues responsible for binding to PA63. The C-terminal region contains the calmodulin-dependent activation domain and the catalytic site. This region is composed of three globular domains: CA, CB and a helical domain connected to CA by a linker. The active site lies at the interface of CA and CB. The metal ion is coordinated by residues from CA; calmodulin probably binds in a multistep fashion first to residues in CA and then to residues present in the linker and the helical domain.
The PA-binding region is found in both B.anthracis EF and LF.

Sequence similaritiesi

Belongs to the adenylyl cyclase class-2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

HOGENOMiHOG000034573.
KOiK11029.
OMAiDKFEVFQ.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR005165. Anthrax_toxin_edema_cen.
IPR003541. Anthrax_toxin_lethal/edema.
IPR014781. Anthrax_toxin_lethal/edema_N/C.
IPR024079. MetalloPept_cat_dom.
[Graphical view]
PfamiPF03497. Anthrax_toxA. 1 hit.
PF07737. ATLF. 1 hit.
[Graphical view]
PRINTSiPR01392. ANTHRAXTOXNA.

Sequencei

Sequence statusi: Complete.

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

P40136-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTRNKFIPNK FSIISFSVLL FAISSSQAIE VNAMNEHYTE SDIKRNHKTE
60 70 80 90 100
KNKTEKEKFK DSINNLVKTE FTNETLDKIQ QTQDLLKKIP KDVLEIYSEL
110 120 130 140 150
GGEIYFTDID LVEHKELQDL SEEEKNSMNS RGEKVPFASR FVFEKKRETP
160 170 180 190 200
KLIINIKDYA INSEQSKEVY YEIGKGISLD IISKDKSLDP EFLNLIKSLS
210 220 230 240 250
DDSDSSDLLF SQKFKEKLEL NNKSIDINFI KENLTEFQHA FSLAFSYYFA
260 270 280 290 300
PDHRTVLELY APDMFEYMNK LEKGGFEKIS ESLKKEGVEK DRIDVLKGEK
310 320 330 340 350
ALKASGLVPE HADAFKKIAR ELNTYILFRP VNKLATNLIK SGVATKGLNV
360 370 380 390 400
HGKSSDWGPV AGYIPFDQDL SKKHGQQLAV EKGNLENKKS ITEHEGEIGK
410 420 430 440 450
IPLKLDHLRI EELKENGIIL KGKKEIDNGK KYYLLESNNQ VYEFRISDEN
460 470 480 490 500
NEVQYKTKEG KITVLGEKFN WRNIEVMAKN VEGVLKPLTA DYDLFALAPS
510 520 530 540 550
LTEIKKQIPQ KEWDKVVNTP NSLEKQKGVT NLLIKYGIER KPDSTKGTLS
560 570 580 590 600
NWQKQMLDRL NEAVKYTGYT GGDVVNHGTE QDNEEFPEKD NEIFIINPEG
610 620 630 640 650
EFILTKNWEM TGRFIEKNIT GKDYLYYFNR SYNKIAPGNK AYIEWTDPIT
660 670 680 690 700
KAKINTIPTS AEFIKNLSSI RRSSNVGVYK DSGDKDEFAK KESVKKIAGY
710 720 730 740 750
LSDYYNSANH IFSQEKKRKI SIFRGIQAYN EIENVLKSKQ IAPEYKNYFQ
760 770 780 790 800
YLKERITNQV QLLLTHQKSN IEFKLLYKQL NFTENETDNF EVFQKIIDEK
Length:800
Mass (Da):92,478
Last modified:February 1, 1995 - v1
Checksum:iF4F7EB485DF4C5A6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti350V → E in AAA79215 (PubMed:3149607).Curated1
Sequence conflicti510Q → T AA sequence (PubMed:3149607).Curated1
Sequence conflicti512 – 513EW → RM AA sequence (PubMed:3149607).Curated2
Sequence conflicti760V → L in CAA00652 (Ref. 3) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23179 Genomic DNA. Translation: AAA22374.1.
M24074 Genomic DNA. Translation: AAA79215.1.
A07289 Unassigned DNA. Translation: CAA00652.1. Sequence problems.
AF065404 Genomic DNA. Translation: AAD32426.1.
AE011190 Genomic DNA. Translation: AAM26089.1.
AE017336 Genomic DNA. Translation: AAT28883.2.
AJ413930 Genomic DNA. Translation: CAC93924.1.
AJ413931 Genomic DNA. Translation: CAC93925.1.
PIRiB59106.
JS0029.
RefSeqiNP_052818.1. NC_001496.1.
WP_000197748.1. NZ_LHUO01000026.1.

Genome annotation databases

EnsemblBacteriaiAAM26089; AAM26089; BX_A0142.
AAT28883; AAT28883; GBAA_pXO1_0142.
GeneIDi3361726.
KEGGibar:GBAA_pXO1_0142.
PATRICi24662079. VBIBacAnt106580_0129.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23179 Genomic DNA. Translation: AAA22374.1.
M24074 Genomic DNA. Translation: AAA79215.1.
A07289 Unassigned DNA. Translation: CAA00652.1. Sequence problems.
AF065404 Genomic DNA. Translation: AAD32426.1.
AE011190 Genomic DNA. Translation: AAM26089.1.
AE017336 Genomic DNA. Translation: AAT28883.2.
AJ413930 Genomic DNA. Translation: CAC93924.1.
AJ413931 Genomic DNA. Translation: CAC93925.1.
PIRiB59106.
JS0029.
RefSeqiNP_052818.1. NC_001496.1.
WP_000197748.1. NZ_LHUO01000026.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K8TX-ray2.60A291-800[»]
1K90X-ray2.75A/B/C291-800[»]
1K93X-ray2.95A/B/C291-800[»]
1LVCX-ray3.60A/B/C291-800[»]
1PK0X-ray3.30A/B/C292-798[»]
1S26X-ray3.00A/B/C291-800[»]
1SK6X-ray3.20A/B/C291-800[»]
1XFUX-ray3.35A/B/C/D/E/F64-800[»]
1XFVX-ray3.35A/B/C/D/E/F33-800[»]
1XFWX-ray3.40A/B/C/D/E/F33-800[»]
1XFXX-ray3.20A/B/C/D/E/F33-800[»]
1XFYX-ray3.30A/B/C/D/E/F33-800[»]
1XFZX-ray3.25A/B/C/D/E/F33-800[»]
1Y0VX-ray3.60A/B/C/D/E/F33-800[»]
DisProtiDP00395.
ProteinModelPortaliP40136.
SMRiP40136.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-31055N.
IntActiP40136. 3 interactors.

Chemistry databases

BindingDBiP40136.
ChEMBLiCHEMBL5396.

Proteomic databases

PRIDEiP40136.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAM26089; AAM26089; BX_A0142.
AAT28883; AAT28883; GBAA_pXO1_0142.
GeneIDi3361726.
KEGGibar:GBAA_pXO1_0142.
PATRICi24662079. VBIBacAnt106580_0129.

Phylogenomic databases

HOGENOMiHOG000034573.
KOiK11029.
OMAiDKFEVFQ.

Enzyme and pathway databases

BioCyciANTHRA:GBAA_PXO1_0142-MONOMER.
ReactomeiR-HSA-5210891. Uptake and function of anthrax toxins.

Miscellaneous databases

EvolutionaryTraceiP40136.
PROiP40136.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR005165. Anthrax_toxin_edema_cen.
IPR003541. Anthrax_toxin_lethal/edema.
IPR014781. Anthrax_toxin_lethal/edema_N/C.
IPR024079. MetalloPept_cat_dom.
[Graphical view]
PfamiPF03497. Anthrax_toxA. 1 hit.
PF07737. ATLF. 1 hit.
[Graphical view]
PRINTSiPR01392. ANTHRAXTOXNA.
ProtoNetiSearch...

Entry informationi

Entry nameiCYAA_BACAN
AccessioniPrimary (citable) accession number: P40136
Secondary accession number(s): Q937W4, Q937W5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 30, 2016
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

EF binds to the heptamer formed by cleaved PA on the host cell membrane. This step is followed by internalization of the hetero-oligomeric complex by receptor-mediated endocytosis. EF requires passage through an acidic vesicle for activity. At acidic pH, the pore is inserted into the membrane, allowing translocation of EF, which probably contributes actively to its own insertion into the membrane. EF remains associated to the vesicle membrane after translocation to the cytosol, with the catalytic domains being exposed on the cytoplasmic face.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Plasmid, 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.