VIOLIN: Vaccine Investigation and Online Information Network

Actinobacillus pleuropneumoniae

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. apfA (Protective antigen)
2. apxIA (Protective antigen)
3. apxIIA (Protective antigen)
4. apxIIIA (Protective antigen)
5. cpxD (Protective antigen)
6. fhuA (Protective antigen)
7. hbpA (Protective antigen)
8. hflX (Protective antigen)
9. hypothetical protein APL_1061 (Protective antigen)
10. lip40 (Protective antigen)
11. omlA (Protective antigen)
12. ompA (Protective antigen)
13. ompW (Protective antigen)
14. potD2 (Protective antigen)
15. tfbA (Protective antigen)
16. tonB2 (Protective antigen)
17. apxIA (Virmugen)
18. ApxIC (Virmugen)
19. apxIIA (Virmugen)
20. ApxIIC (Virmugen)
21. apxIIIB (Virmugen)
22. apxIIID (Virmugen)
23. ApxIVA (Virmugen)
24. ureC (Virmugen)
Vaccine Related Host Genes
1. A2M
2. Ighg1
3. Ighv1-9
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

715

2. Disease:

porcine pleuropneumonia

3. Introduction

The bacterium Actinobacillus pleuropneumoniae (App) was previously called Haemophilus pleuropneumoniae and there are at least twelve different strains, some of which produce no disease and are non pathogenic, but others cause very severe disease. Strains 1, 5, 9, 11 and 12 are highly virulent and strains 3 and 6 are very mild. The organism is carried in the tonsils and respiratory tract and the incubation period is very short, from as little as 12 hours through to three days. It is transmitted by droplet infection between one pig and another. The organism may survive in discharges, serum etc. for up to 5 days. Contact with dead stock is therefore important from biosecurity. It dies quickly if dried, but it may persist in water for 20 days or more. App can survive in the lungs and tonsils for long periods of at least 4 months. It is probably airborne for only 5 to 10 metres. Disease is dose dependent i.e. the more bacteria the pig is exposed to the more severe will be the disease. Infection is spread from one pig to another by nose to nose contact. Pigs may be infected with different serotypes simultaneously. PRRS and EP can make the disease worse. In a naïve herd up to 30% of animals may be affected. When App attacks the lungs the toxins produced cause severe damage to the tissues which turn blue to black (necrosis) with extensive pleurisy. The chest cavity rapidly fills up with fluid.

The organism may affect the pig from weaning through to slaughter but usually the age is from 8 to 16 weeks, once maternal antibody has disappeared. Sudden death is often the only sign with blood and froth discharged from the nose. In the live pig a short cough may be heard with signs of severe breathing difficulties and blueing of the ears. Badly affected pigs are severely depressed. Body temperature is often high. Death is due to a combination of heart failure and the toxins produced by the organisms (ThePigSite Pig Health).

4. Microbial Pathogenesis

Actinobacillus pleuropneumoniae interacts closely with epithelial cells in the lower respiratory tract and toxins produced during infection are delivered directly to the cell surface. This close association between A. pleuropneumoniae and respiratory epithelial cells may impair the binding of specific antibodies to the Apx toxins, resulting in development of necrosis and hemorrhage (Haesebrouck et al., 2004).

5. Host Ranges and Animal Models

Pigs are the main host, and mice can serve as a model of infection (Shin et al., 2007).

6. Host Protective Immunity

Protection is mediated by antibodies and mucosal immunity (Shin et al., 2007).

II. Vaccine Related Pathogen Genes

1. apfA

Gene Name : apfA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : AAO64346
Other Database IDs : CDD:331644
Taxonomy ID : 228399
Protein Name : major type IV fimbrial subunit precursor
Protein pI : 7.91
Protein Weight : 15710.73
Protein Length : 259
Protein Note : ApfA

Protein Sequence : Show Sequence

>AAO64346.1 major type IV fimbrial subunit precursor [Actinobacillus pleuropneumoniae serovar 1 str. 4074]
MQKLSLIRPLTNAFTLIELMIVIAIIAILATVAIPSYNSYTQKAALSELLAASASYKTDVEICIYNTGDS
KNCSGGQNGVRKMTELRQAKYLNAITVEGGTITVTGKGNLQEYGYTMTPIHNGSTISWETKCKGEDLSLF
PANFCASN

Molecule Role : Protective antigen
Molecule Role Annotation : Purified recombinant ApfA elicited an elevated humoral immune response and conferred robust protection against challenges with A. pleuropneumoniae serovar 1 strain 4074 and serovar 7 strain WF83 in mice (Zhou et al., 2013).
Related Vaccine(s): A. pleuropneumoniae apfA vaccine

2. apxIA

Gene Name : apxIA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae L20
NCBI Gene ID : 4850247
NCBI Protein GI : 126208908
Locus Tag : APL_1444
Genbank Accession : CP000569
Protein Accession : YP_001054133
Taxonomy ID : 416269
Gene Starting Position : 1652926
Gene Ending Position : 1655994
Gene Strand (Orientation) : -
Protein Name : RTX-I toxin determinant A
Protein pI : 5.34
Protein Weight : 104673.05
Protein Length : 1022
Protein Note : pubmed:8359891

DNA Sequence : Show Sequence

>gi|126207488:1652926-1655994 Actinobacillus pleuropneumoniae L20, complete genome
CTTAAGCAGATTGTGTTAAATAATTACTGAAAGCATTCGGTATGCTATTCGGTGAATTGCTGTAAGCTAA
TGGACCGCCTGCTCCCACTAAAACTTGTCCGTGTTCACCGGTAAGTGCACCAGTAGATGAAATGATTTGT
TCAATATCTTTTCTGAGTTGAGGAAGTGCATTATATCCTTCTCCATAATACAATTTTTCTTCTAACCCAT
TAAAGTAATTGATACCTCTTCCAGGAGCTGTCAGTTCAGTCAGATATTGGCTTAAAACATAAGCTCCATC
TTTATCAACGATTTTTTCAATTTTATTATTTTGTCCTTCTTTACCTTCCTTGAACCAATCTTTAATCGTG
AGCGCATTCCCATTGTAATCTTCATGGTAATACAGTGTTCCTCCGATTCTTTTATTCACAAGAAGATCAT
CACCGATTCTGATAAATCCTACATCTTTAAAACTAAGATCCGATAACAATAACGTATCATCATCACCGCC
TTTCTCAATAATGATATGACGACCGTACTCCTTACTGTAGCGATAAATATCCTTACCTAAACCACCGTAG
ATTTTGTCATTGCCTACACCACCGTCAAATAAGTTAGTACCATCGCTGCCATACAGAATGTCATTACCCG
CACCACCTAATAATACGTTGTATTGACCCTCAAAGACCTGCAACTCATCGTCACCATCACCGCCATTAAG
GAAATTATTACCTTTTCCGCCGATTAATCGGTCGTTTCCGTTACCACCAACAAGATGGTCGTTACCGTCA
CCGCCATGGATTACATCATTACCGTCGTCTCCGTATAAGATATCGTGGCCGTCATTACCGTAGATTTCAT
CATCGCCTTTCGCACCATGGAAAATATCGGTAAAGCGACTACCAAAGAATTTGTCTTTACGATTACTACC
GATAATTTCTTCAACAGAATGTAATTCATCTTTAGCTCTGATACCGTTCCCAAGTTCGAATGGGCTTAAC
TCATAATCACGATATTCTAATTTTTCACTGCGTTTTCCAACTGAAATATCCTGAGTTTTAACCACTTCTT
TTAAAACTTTTACATCAGCTTTAAGTTCTTTAGTGACAATATATTCACCGGCTTTCTGTGCACTTTGTCC
GTCAAATGTTAAGTAACCTGTATCGGTTTTATCGTAATATGCTACATCATGTCCGTTACCCGCATATACG
ATAGATGAACCGGATGAAAGATATATACGATCATTTTTCTCACCCAAATGAGATTCAATGGTCACTTGAC
GTTTTTCACCTTTTTTATCTATCGCTAATTGGATAAGATTCGTATAGTCATAAATCGCATTATGTGACTG
CACACCGGTTACCACCCATTTTTCTTTACCTTTAACGAATAATTCGGTCATATATTCGTATTTACCGGTT
TGCTTACGCTCACGAATCTCTTCACCTGCGGTAAAAACCGGTGTAATAAATTTCAATAAAGTGGTTTTGT
TAATTGAAGAAAGGTCGATTTTGCCTTCAAGCGGATCAAACACTTTTTTATCAAAACGATCCGGATCTTT
CTCTAACAATTTTCCTTCTTCAAAGAAATCGACATAAGCCTTACCGCTTTTCGCATCCGCACCTTTACGC
GTGATACCGGCAAGTTCCCCGATATTGACATCCCAACGTTGTTGCGTAATAGCAACGACACGCTCTACCG
AATACTCTTTATTGTATTGTGATAACAATTCAAAGGTATCTTCTAAGAATGCGGAATGGCGGGCGTCATA
ACCGTTTTCAAAATAGTTTTTACCGTGTTTTTTCTCCCATTCGTCAATCTTATTCGCTAATTTCGTTGCA
ACTCGTTCGAAGATTGCCTGTTTAGAAGCATCTAAAATACCTGAAATAATACCGGTGATTGCACTAACTA
AAGCTGCTACCGGCGCACCGACTAATGAGCCGGTTGCAGCAGCCCCAACACCTGCGGAAGCCGCACTTAA
CACACTGTTAATCGTGGTTAATGCCGCTTCAATCGCACCGGTTTCACGGTAGAATGAAGCTAATAAACTA
TCACCTTCATAACCGAACTTTTTAAAGCGCTCCGAATATTGTTCAAGCTGTTTCGCACGTTCAAACTTAT
CCGCAACATTTAAGAACGAAAGCGGGCTAATCGCTAATGCTACGACCGAACCGATTAAACCACCGGTTGC
CGCAGTTGTGGATAAGCCTGCCGCCACACGTTGCGCAATAATATATTGAGAAACCGCTTTACCGATATTG
CCTAAGATTTTAGTTGAGATTTCAATACCTGCCGCCGCTTTTGTACCTGCATCGGCATCTTTATTACTTA
AAATGAATGAAGCCGAAACAACAGATAAGATACCTGATACGGCATCAAACCCAGGTCCTGCAAGGCTTAA
ATCTGGAAGGTTATTTAACTTACTTGCTAAACCGCTTAAGCGAGTGTTAGATAAGGCATTGCCCAATTTA
CCTAATTGTTCGGCAAACGCATCCACCGTACCCGTTGCACTTGCAATGTTATCCACTAACTGAGCGGCTA
GATCCACACCCGCTTTAGCTAATTCCGAACCACTGACGTCCTCACCGTTTCTACGGCGACGAAGCAGGCT
ATCAAGATCCATACCCGCAATAGCCGTACCTAAGAAACTTTGTAAGGCTGAAAGTGCCGTTTGCGTTTTA
TTTAAACGTTGTCCTAATGCTTCCGATGAACCGCCGAGCGATTTACTTAATTTTTGGTTCTTATTCAGTA
ACTTATCAAACTGAGGTGCAAATAATGCGATGCCTCGTTCCGAGAAACCTAATAGTTTTTCCGTTGTACC
GAATAATTCTTTCGCTAGTGCGGTACCGTTTTTTTCCGAGCGATGTACTTCGATCCCTAAAGCCTCCGCC
GCTTTCACTAAATCATTAAGACTTGAGCCGGTACTAGCTTGATAATCTTTCGGAATATATAAAATTAATT
TCTGCCCTGCTTGCTTCACCTGTCCCAAACCATTTTTTAATGCGCCGGCACCTGATTTAGCTGCACTTTT
TGTATGTTGATTAAGTGAATCAATCAATCCTTTGACTCTATCGAGCTGAGAGTTAGCCA

Protein Sequence : Show Sequence

>gi|126208908|ref|YP_001054133.1| RTX-I toxin determinant A [Actinobacillus pleuropneumoniae L20]
MANSQLDRVKGLIDSLNQHTKSAAKSGAGALKNGLGQVKQAGQKLILYIPKDYQASTGSSLNDLVKAAEA
LGIEVHRSEKNGTALAKELFGTTEKLLGFSERGIALFAPQFDKLLNKNQKLSKSLGGSSEALGQRLNKTQ
TALSALQSFLGTAIAGMDLDSLLRRRRNGEDVSGSELAKAGVDLAAQLVDNIASATGTVDAFAEQLGKLG
NALSNTRLSGLASKLNNLPDLSLAGPGFDAVSGILSVVSASFILSNKDADAGTKAAAGIEISTKILGNIG
KAVSQYIIAQRVAAGLSTTAATGGLIGSVVALAISPLSFLNVADKFERAKQLEQYSERFKKFGYEGDSLL
ASFYRETGAIEAALTTINSVLSAASAGVGAAATGSLVGAPVAALVSAITGIISGILDASKQAIFERVATK
LANKIDEWEKKHGKNYFENGYDARHSAFLEDTFELLSQYNKEYSVERVVAITQQRWDVNIGELAGITRKG
ADAKSGKAYVDFFEEGKLLEKDPDRFDKKVFDPLEGKIDLSSINKTTLLKFITPVFTAGEEIRERKQTGK
YEYMTELFVKGKEKWVVTGVQSHNAIYDYTNLIQLAIDKKGEKRQVTIESHLGEKNDRIYLSSGSSIVYA
GNGHDVAYYDKTDTGYLTFDGQSAQKAGEYIVTKELKADVKVLKEVVKTQDISVGKRSEKLEYRDYELSP
FELGNGIRAKDELHSVEEIIGSNRKDKFFGSRFTDIFHGAKGDDEIYGNDGHDILYGDDGNDVIHGGDGN
DHLVGGNGNDRLIGGKGNNFLNGGDGDDELQVFEGQYNVLLGGAGNDILYGSDGTNLFDGGVGNDKIYGG
LGKDIYRYSKEYGRHIIIEKGGDDDTLLLSDLSFKDVGFIRIGDDLLVNKRIGGTLYYHEDYNGNALTIK
DWFKEGKEGQNNKIEKIVDKDGAYVLSQYLTELTAPGRGINYFNGLEEKLYYGEGYNALPQLRKDIEQII
SSTGALTGEHGQVLVGAGGPLAYSNSPNSIPNAFSNYLTQSA

Molecule Role : Virmugen
Molecule Role Annotation : The mutant strain, with deletion of apxIA gene, obtained in this study offered a level of cross-serovar protection against A. pleuropneumoniae infection in mice and pigs (Xu et al., 2006).
Related Vaccine(s): Actinobacillus pleuropneumoniae apxIA mutant vaccine

3. apxIA

Gene Name : apxIA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
VO ID : VO_0011019
NCBI Protein GI : 312899
Other Database IDs : CDD:308152
CDD:225483
CDD:311996
GOA:P55128
InterPro: IPR001343
InterPro: IPR003995
InterPro: IPR011049
InterPro: IPR013550
InterPro: IPR018504
InterPro: IPR018511
UniProtKB/UniProt: P55128
Taxonomy ID : 754346
Gene Strand (Orientation) : ?
Protein pI : 5.41
Protein Weight : 104857.1
Protein Length : 1100
Protein Note : RTX N-terminal domain; pfam02382

Protein Sequence : Show Sequence

>CAA51548.1 apxIA [Actinobacillus pleuropneumoniae serovar 9]
MANSQLDRVKGLIDSLNQHTKSAAKSGAGALKNGLGQVKQAGQKLILYIPKDYQASTGSSLNDLVKAAEA
LGIEVHRSEKNGTALAKELFGTTEKLLGFSERGIALFAPQFDKLLNKNQKLSKSLGGSSEALGQRLNKTQ
TALSALQSFLGTAIAGMDLDSLLRRRRNGEDVSGSELAKAGVDLAAQLVDNIASATGTVDAFAEQLGKLG
NALSNTRLSGLASKLNNLPDLSLAGPGFDAVSGILSVVSASFILSNKDADAGTKAAAGIEISTKILGNIG
KAVSQYIIAQRVAAGLSTTAATGGLIGSVVALAISPLSFLNVADKFERAKQLEQYSERFKKFGYEGDSLL
ASFYRETGAIEAALTTINSVLSAASAGVGAAATGSLVGAPVAALVSAITGIISGILDASKQAIFERVATK
LANKIDEWEKKHGKNYFENGYDARHSAFLEDTFELLSQYNKEYSVERVVAITQQRWDVNIGELAGITRKG
SDTKSGKAYVDFFEEGKLLEKEPDRFDKKVFDPLEGKIDLSSINKTTLLKFVTPVFTAGEEIRERKQTGK
YEYMTELFVKGKEKWVVTGVQSHNAIYDYTNLIQLAIDKKGEKRQVTIESHLGEKNDRIYLSSGSSIVYA
GNGHDVAYYDKTDTGYLTFDGQSAQKAGEYIVTKELKADVKVLKEVVKTQDISVGKRSEKLEYRDYELSP
FELGNGIRAKDELHSVEEIIGSNRKDKFFGSRFTDIFHGAKGDDEIYGNDGHDILYGDDGNDVIHGGDGN
DHLVGGNGNDRLIGGKGNNFLNGGDGDDELQVFEGQYNVLLGGAGNDILYGSDGTNLFDGGVGNDKIYGG
LGKDIYRYSKEYGRHIIIEKGGDDDTLLLSDLSFKDVGFIRIGDDLLVNKRIGGTLYYHEDYNGNALTIK
DWFKEGKEGQNNKIEKIVDKDGAYVLSQYLTELTAPGRGINYFNGLEEKLYYGEGYNALPQLRKDIEQII
SSTGAFTGDHGKVSVGSGGPLVYNNSANNVANSLSYSLAQAA

Molecule Role : Protective antigen
Molecule Role Annotation : The ApxI antigen is an important factor in the protection against Actinobacillus pleuropneumoniae serotype 5 infection; therefore, the protective immunity in mice following oral immunization with Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) was compared with that in two control groups (group A and B). The immunogenicity of the rApxIA antigen derived from the yeast was confirmed by a high survival rate and an ApxIA-specific IgG antibody response (p < 0.01) (Shin et al., 2007).
Related Vaccine(s): A. pleuropneumoniae ApxIa and ApxIIa protein vaccine , A. pleuropneumoniae ApxIA protein vaccine , A. pleuropneumoniae DNA vaccine pcDNA-apxIA/pcDNA-apxIIA , HS93Tox-/pIG-T1K , mixture of Salmonella strains delivering ApxIA, ApxIIA, ApxIIIA and OmpA of A. pleuropneumoniae , rS.C-APP-ApxI/ApxII

4. ApxIC

Gene Name : ApxIC
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : 1477456
Other Database IDs : CDD:154216
Taxonomy ID : 715
Gene Strand (Orientation) : ?
Protein Length : 172
Protein Note : RTX toxin acyltransferase family; cl01131

Protein Sequence : Show Sequence

>gi|1477456|gb|AAB17219.1| apxIC [Actinobacillus pleuropneumoniae]
MSKKINGFEVLGEVAWLWASSPLHRKWPLSLLAINVLPAIESNQYVLLKRDGFPIAFCSWANLNLENEIK
YLDDVASLVADDWTSGDRRWFIDWIAPFGDSAALYKHMRDNFPNELFRAIRVDPDSRVGKISEFHGGKID
KKLASKIFQQYHFELMSELKNKQNFKFSLVNS

Molecule Role : Virmugen
Molecule Role Annotation : In the intra-peritoneal mouse model, the virulence of the mutant strain decreased at least 100 fold compared with the parent strain. The mutant was evaluated as a potential vaccine using a vaccination-challenge trial. The death number and lung lesion score in the vaccinated pigs given the serovar 1 challenge were obviously lower than those in the unvaccinated pigs (Xu et al., 2007).
Related Vaccine(s): Actinobacillus pleuropneumoniae ApxIC mutant vaccine

5. apxIIA

Gene Name : apxIIA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
VO ID : VO_0011020
NCBI Protein GI : 52630374
Other Database IDs : CDD:280531
CDD:225483
CDD:305016
CDD:285531
Taxonomy ID : 715
Gene Strand (Orientation) : ?
Protein Name : ApxIIA
Protein pI : 5.5
Protein Weight : 96615.24
Protein Length : 1024
Protein Note : biovar: 1

Protein Sequence : Show Sequence

>AAU84700.1 ApxIIA [Actinobacillus pleuropneumoniae]
MSKITLSSLKSSLQQGLKNGKNKLNQAGTTLKNGLTQTGHSLQNGAKKLILYIPQGYDSGQGNGVQDLVK
AANDLGIEVWREERSNLDIAKTSFDTTQKILGFTDRGIVLFAPQLDNLLKKNPKIGNTLGSASSISQNIG
KANTVLGGIQSILGSVLSGVNLNELLQNKDPNQLELAKAGLELTNELVGNIASSVQTVDAFAEQISKLGS
HLQNVKGLGGLSNKLQNLPDLGKASLGLDIISGLLSGASAGLILADKEASTEKKAAAGVEFANQIIGNVT
KAVSSYILAQRVASGLSSTGPVAALIASTVALAVTPLSFLNVADKFKQADLIKSYSERFQKLGYDGDRLL
ADFHRETGTIDASVTTINTALAAISGGVGAASAGSLVGAPVALLVAGVTGLITTILEYSKQAMFEHVANK
VHDRIVEWEKKHNKNYFEQGYDSRHLADLQDNMKFLINLNKELQAERVVAITQQRWDNQIGDLAAISRRT
DKISSGKAYVDAFEGGQHQSYDSSVQLDNKNGIINISNTNRKTQSVLFRTPLLTPGEENRERIQEGKNSY
ITKLHIQRVDSWTVTDGDASSSVDFTNVVQRIAVKFDDAGNIIESKDTKIIANLGAGNDNVFVGSSTTVI
DGGDGHDRVHYSRGEYGALVIDATAETEKGSYSVKRYVGDSKALHETIATHQTNVGNREEKIEYRREDDR
FHTGYTVTDSLKSVEEIIGSQFNDIFKGSQFDDVFHGGNGVDTIDGNDGDDHLFGGAGDDVIDGGNGNNF
LVGGTGNDIISGGKDNDIYVHKTGDGNDSITDSGGQDKLAFSDVNLKDLTFKKVDSSLEIINQKGEKVRI
GNWFLEDDLASTVANYKATNDRKIEEIIGKGGERITSEQVDKLIKEGNNQISAEALSKVVNDYNTSKDRQ
NVSNSLAKLISPVGSFTSSSDFRNNLGTYVPSSIDVSNNIQLARAA

Molecule Role : Protective antigen
Molecule Role Annotation : The levels of local and systemic antibodies specific to the Apx antigens were investigated in mice orally immunized with Apx antigen-expressing yeast. Specific IgA responses to ApxIA or ApxIIA in the intestines and lungs from mice immunized with yeast expressing Apx antigens were significantly higher than those in the control groups after the second and third immunizations, respectively (p < 0.05). All mice were monitored for up to 72 h after challenge with the MLD of an A. pleuropneumoniae field isolate. Overall, the final survival rates of the vaccinated groups were higher than those of the control groups at each time point (Shin et al., 2007).
Related Vaccine(s): A. pleuropneumoniae ApxIa and ApxIIa protein vaccine , A. pleuropneumoniae DNA vaccine pcDNA-apxIA/pcDNA-apxIIA , mixture of Salmonella strains delivering ApxIA, ApxIIA, ApxIIIA and OmpA of A. pleuropneumoniae , rS.C-APP-ApxI/ApxII

6. apxIIA

Gene Name : apxIIA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serotype 2
NCBI Protein GI : 255959000
Locus Tag : APL_0956
Genbank Accession : CP000569
Protein Accession : YP_001053657
Other Database IDs : CDD:111291
CDD:116920
Taxonomy ID : 715
Gene Starting Position : 1095617
Gene Ending Position : 1098487
Gene Strand (Orientation) : -
Protein Name : RTX-II toxin determinant A
Protein pI : 5.34
Protein Weight : 96054.51
Protein Length : 956
Protein Note : RTX N-terminal domain; pfam02382

DNA Sequence : Show Sequence

>gi|126207488:1095617-1098487 Actinobacillus pleuropneumoniae L20, complete genome
ATTAAGCGGCTCTAGCTAATTGAATATTATTCGAGACATCTATTGATGAAGGAACATATGTTCCTAAATT
ATTCCTAAAGTCTGAGGAAGACGTAAAGCTCCCGACTGAAGAAATCAATTTTGCTAAGCTATTAGATACG
TTCTGTCTATCTTTACTCGTATTGTAATCATTCACAACTTTGGATAATGCTTCTGCAGAGATTTGATTGT
TACCCTCCTTAATCAGTTTATCAACTTGTTCTGATGTAATACGTTCTCCTCCTTTACCAATAATTTCCTC
AATTTTTCGGTCATTCGTAGCTTTATAGTTAGCAACTGTGCTAGCCAAATCATCTTCTAAGAACCAATTC
CCAATACGAACTTTTTCTCCTTTTTGATTAATGATTTCGAGAGAAGAATCTACTTTCTTAAAGGTGAGGT
CTTTAAGATTTACATCCGAAAATGCCAGTGTATCTTGTCCGCCAGAGTCTGTAATAGAATCATTTCCATC
GCCTGTTTTATGGACATATATATCATTATCTTTACCTCCCGAGATAATATCATTACCGGTTCCTCCAACA
AGGAAATTGTTACCGTTTCCTCCATCGATAACATCATCGCCTGCGCCACCAAATAAATGATCGTCACCAT
CGTTACCATCAATAGTGTCTACACCATTACCACCATGGAACACATCATCAAATTGGCTTCCTTTGAAAAT
ATCATTAAATTGTGAACCAATGATCTCTTCAACTGATTTGAGTGAGTCCGTCACAGTATAACCAGTATGA
AAACGATCATCTTCACGACGATATTCAATTTTTTCTTCACGATTACCAACATTTGTTTGGTGGGTGGCAA
TTGTTTCATGTAATGCTTTACTGTCTCCGACATAGCGTTTTACTGAATATGAGCCTTTTTCTGTCTCGGC
TGTAGCATCAATAACTAATGCGCCATATTCTCCTCTACTGTAGTGAACTCGATCATGTCCGTCCCCGCCA
TCAATAACGGTAGTACTTGACCCAACAAATACATTATCGTTACCAGCACCTAAATTTGCGATAATTTTAG
TATCTTTAGATTCGATAATGTTACCTGCATCATCAAATTTCACAGCGATTCGTTGTACTACATTAGTGAA
ATCTACGCTTGAGCTAGCATCACCATCTGTTACAGTCCAACTGTCAACTCTTTGTATATGTAATTTTGTA
ATATAAGAATTTTTACCTTCCTGAATACGTTCCCGATTCTCTTCACCTGGAGTTAGTAATGGAGTTCTGA
ATAAAACACTTTGTGTCTTTCTATTTGTATTACTAATATTAATAATACCGTTTTTGTTATCTAGCTGTAC
GGATGAATCGTAGGACTGGTGTTGCCCCTCCTCAAAAGCATCCACATAAGCTTTTCCACTGGAAATTTTA
TCCGTTCTACGGCTAATTGCCGCTAGGTCTCCAATTTGGTTATCCCATCTTTGTTGGGTAATAGCTACTA
CGCGTTCAGCCTGAAGTTCTTTATTTAAATTGATAAGAAACTTCATATTGTCTTGTAAATCAGCTAAATG
ACGAGAATCATAACCTTGCTCAAAATAGTTTTTATTATGTTTTTTCTCCCATTCAACTATTCTGTCATGA
ACCTTATTTGCAACATGTTCAAACATGGCTTGTTTAGAATATTCTAGAATAGTTGTAATAAGTCCCGTAA
CACCAGCAACGAGTAACGCAACTGGAGCTCCGACTAGAGAACCCGCGCTTGCAGCTCCAACTCCACCGGA
GATAGCTGCTAAAGCAGTGTTAATTGTTGTTACAGAAGCATCAATAGTTCCTGTCTCACGGTGAAAATCA
GCTAATAAACGATCTCCATCATATCCTAATTTTTGGAAGCGTTCAGAATATGATTTGATTAAATCAGCTT
GTTTAAACTTATCAGCTACATTTAAGAATGAAAGAGGGCTAACAGCTAGTGCAACTGTAGATGCGATTAA
TGCAGCGACAGGACCAGTTGAAGACAAACCTGAAGCGACTCGTTGGGCAAGAATGTAAGATGAGACCGCT
TTTGTTACATTACCTATAATTTGGTTAGCAAATTCTACACCTGCGGCAGCTTTCTTTTCTGTTGAAGCCT
CTTTATCTGCTAAAATGAGACCTGCAGATGCTCCAGAAAGTAAACCAGAGATAATGTCCAAACCTAAACT
TGCTTTTCCTAGATCTGGTAGATTTTGTAATTTATTACTCAATCCTCCTAATCCTTTCACATTCTGTAAA
TGTGAACCTAGTTTAGATATTTGTTCTGCAAATGCATCTACAGTTTGCACCGAGCTAGCAATATTACCAA
CTAATTCATTAGTCAGTTCTAGCCCTGCTTTTGCAAGTTCTAATTGATTAGGATCTTTATTTTGAAGTAA
TTCATTCAGATTTACTCCAGATAAAACAGATCCTAAAATAGATTGAATACCACCTAATACAGTATTGGCT
TTACCTATATTTTGTGAGATGCTAGAAGCACTTCCTAATGTATTGCCAATTTTAGGATTCTTCTTTAATA
AATTATCTAGCTGAGGTGCAAATAATACAATTCCTCTATCAGTAAAACCTAGAATTTTCTGAGTTGTATC
AAAGCTAGTTTTTGCAATGTCCAAATTGCTGCGTTCTTCTCGCCATACTTCAATACCTAAATCATTAGCA
GCTTTAACTAAATCTTGAACTCCATTTCCTTGACCCGAATCATAGCCTTGAGGAATATATAAGATTAATT
TTTTAGCCCCATTCTGTAGAGAATGACCAGTTTGAGTTAAACCATTCTTCAGTGTTGTACCTGCTTGATT
TAACTTGTTTTTCCCATTTTTCAATCCTTGTTGTAAGGACGATTTTAATGATGACAAAGTGATTTTTGAC
A

Protein Sequence : Show Sequence

>gi|255959000|gb|ACU43588.1| RTX-II toxin determinant A [Actinobacillus pleuropneumoniae]
MSKITLSSLKSSLQQGLKNGKNKLNQAGTTLKNGLTQTGHSLQNGAKKLILYIPQGYDSGQGNGVQDLVK
AANDLGIEVWREERSNLDIAKTSFDTTQKILGFTDRGIALFAPQLDNLLKKNPKIGNTLGSASSISQNIG
KANTVLGGIQSILGSVLSGVNLNELLQNKDPNQLELAKAGLELTNELVGNIASSVQTVDAFAEQISKLGS
HLQNVKGLGGLSNKLQNLPDLGKASLGLDIISGLLSGASAGLILADKEASTEKKAAAGVEFANQIIGNVT
KAVSSYILAQRVASGLSSTGPVAALIASTVALAVSPLSFLNVADKFKQADLIKSYSERFQKLGYDGDRLL
ADFHRETGTIDASVTTINTALAAISGGVGAASAGSLVGAPVALLVAGVTGLITTILEYSKQAMFEHVANK
VHDRIVEWEKKHNKNYFEQGYDSRHLADLQDNMKFLINLNKELQAERVVAITQQRWDNQIGDLAAISRRT
DKISSGKAYVDAFEEGQHQSYDSSVQLDNKNGIINISNTNRKTQSVLFRTPLLTPGEENRERIQEGKNSY
ITKLHIQRVDSWTVTDGDASSSVDFTNVVQRIAVKFDDAGNIIESKDTKIIANLGAGNDNVFVGSSTTVI
DGGDGHDRVHYSRGEYGALVIDATAETEKGSYSVKRYVGDSKALHETIATHQTNVGNREEKIEYRREDDR
FHTGYTVTDSLKSVEEIIGSQFNDIFKGSQFDDVFHGGNGVDTIDGNDGDDHLFGGAGDDVIDGGNGNNF
LVGGTGNDIISGGKDNDIYVHKTGDGNDSITDSGGQDKLAFSDVNLKDLTFKKVDSSLEIINQKGEKVRI
GNWFLEDDLASTVANYKATNDRKIEEIIGKGGERITSEQVDKLIKEGNNQISAEALSKVVNDYNTSKDRQ
NVSNSLAKLISSVGSFTSSSDFRNNLGTYVPSSIDVSNNIQLARAA

Molecule Role : Virmugen
Molecule Role Annotation : Deletion in ureC and apxIIA genes of Actinobacillus pleuropneumoniae serotype 2 prototype provides attenuation and protection in pigs against challenge with the virulent parent strain of A. pleuropneumoniae (Tonpitak et al., 2002).
Related Vaccine(s): Actinobacillus pleuropneumoniae ureC and apxIIA double mutant deletion vaccine , rS.C-APP-ApxIIA

7. ApxIIC

Gene Name : ApxIIC
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : 52630373
Other Database IDs : CDD:154216
Taxonomy ID : 715
Gene Strand (Orientation) : ?
Protein Name : ApxIIC
Protein Length : 160
Protein Note : biovar: 1

Protein Sequence : Show Sequence

>gi|52630373|gb|AAU84699.1| ApxIIC [Actinobacillus pleuropneumoniae]
MMLKNDFNVLGQIAWLWANSPMHRNWSVSLLMKNVIPAIENDQYLLLVDDGFPIAYCSWAKLTLESEARY
VKDTNSLKIDDWNAGDRIWIIDWIAPFGDSSLLYKHMRQRFPYDIGRAIRIYPSKKDTGKIIYLKGGKIT
KKVAEKTFLQYEQELITALQ

Molecule Role : Virmugen
Molecule Role Annotation : In the present study, the gene encoding the ApxII-activating protein, apxIIC, was insertionally inactivated on the chromosome of a serovar 7 strain, HS93. Pigs vaccinated with live HS93C-Ampr via the intranasal route were protected against a cross-serovar challenge with a virulent serovar 1 strain of A. pleuropneumoniae (Prideaux et al., 1999).
Related Vaccine(s): A. pleuropneumoniae HS93C-Ampr , Actinobacillus pleuropneumoniae apxIIC and apxIVA double deletion mutant vaccine

8. apxIIIA

Gene Name : apxIIIA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : CAA48711
Other Database IDs : CDD:308152
CDD:225483
CDD:311996
GOA:P55131
InterPro: IPR001343
InterPro: IPR003995
InterPro: IPR011049
InterPro: IPR013550
InterPro: IPR018504
InterPro: IPR018511
UniProtKB/UniProt: P55131
Taxonomy ID : 715
Protein Name : ApxIIIA
Protein pI : 5.56
Protein Weight : 107581.37
Protein Length : 1123
Protein Note : RTX N-terminal domain; pfam02382

Protein Sequence : Show Sequence

>CAA48711.1 apxIIIA [Actinobacillus pleuropneumoniae]
MSTWSSMLADLKKRAEEAKRQAKKGYDVTKNGLQYGVSQAKLQALAAGKAVQKYGNKLVLVIPKEYDGSV
GNGFFDLVKAAEELGIQVKYVNRNELEVAHKSLGTADQFLGLTERGLTLFAPQLDQFLQKHSKISNVVGS
STGDAVSKLAKSQTIISGIQSVLGTVLAGINLNEAIISGGSELELAEAGVSLASELVSNIAKGTTTIDAF
TTQIQNFGKLVENAKGLGGVGRQLQNISGSALSKTGLGLDIISSLLSGVTASFALANKNASTSTKVAAGF
ELSNQVIGGITKAVSSYILAQRLAAGLSTTGPAAALIASSISLAISPLAFLRVADNFNRSKEIGEFAERF
KKLGYDGDKLLSEFYHEAGTIDASITTISTALSAIAAGTAAASAGALVGAPITLLVTGITGLISGILEFS
KQPMLDHVASKIGNKIDEWEKKYGKNYFENGYDARHKAFLEDSFSLLSSFNKQYETERAVLITQQRWDEY
IGELAGITGKGDKLSSGKAYVDYFQEGKLLEKKPDDFSKVVFDPTKGEIDISNSQTSTLLKFVTPLLTPG
TESRERTQTGKYEYITKLVVKGKDKWVVNGVKDKGAVYDYTNLIQHAHISSSVARGEEYREVRLVSHLGN
GNDKVFLAAGSAEIHAGEGHDVVYYDKTDTGLLVIDGTKATEQGRYSVTRELSGATKILREVIKNQKSAV
GKREETLEYRDYELTQSGNSNLKAHDELHSVEEIIGSNQRDEFKGSKFRDIFHGADGDDLLNGNDGDDIL
YGDKGNDELRGDNGNDQLYGGEGNDKLLGGNGNNYLSGGDGNDELQVLGNGFNVLRGGKGDDKLYGSSGS
DLLDGGEGNDYLEGGDGSDFYVYRSTSGNHTIYDQGKSSDLDKLYLSDFSFDRLLVEKVDDNLVLRSNES
SHNNGVLTIKDWFKEGNKYNHKIEQIVDKNGRKLTAENLGTYFKNAPKADNLLNYATKEDQNESNLSSLK
TELSKIITNAGNFGVAKQGNTGINTAALNNEVNKIISSANTFATSQLGGSGMGTLPSTNVNSMMLGNLAR
AA

Molecule Role : Protective antigen
Molecule Role Annotation : The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.(Hur et al., 2016)
Related Vaccine(s): mixture of Salmonella strains delivering ApxIA, ApxIIA, ApxIIIA and OmpA of A. pleuropneumoniae

9. apxIIIB

Gene Name : apxIIIB
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serovar 2
NCBI Nucleotide GI : 470686
Other Database IDs : CDD:30270
CDD:162558
CDD:186074
CDD:73011
Taxonomy ID : 34063
Gene Strand (Orientation) : ?
Protein Name : RTX toxin
Protein Note : A sub-family of peptidase C39 which contains Cyclolysin and Hemolysin processing peptidases. Peptidase family C39 mostly contains bacteriocin-processing endopeptidases from bacteria. The cysteine peptidases in family C39 cleave the 'double-glycine'...; cd02417

DNA Sequence : Show Sequence

>gb|L12145.1|ACNNON:3943-6078 Actinobacillus pleuropneumoniae (serotype 2) RTX toxin III (apxIII CABD) genes, complete cds
ATGGAGTCACAAATGCCTTTTAACGAAAAAATAGATTACGGATTACATGCATTGGTAATTCTCGCGCAAT
ATCACAATGTTGCCGTAAACCCTGAAGAGGTAAAACATAAATTTGATCTTGATGGCAAAGGATTGGATCT
TGTTGCTTGGTTATTAGCAGCAAAATCATTAGAATTAAAAGTCAAACGAGTAAAAAAGAGTATTGAGCGT
TTACCATTTATTCATCTTCCTGCTTTAATCTGGCGAGATGATGGTCAACACGTTATTTTGATGAAAATTG
ACACCCAAACTAACCGTTACCTTATTTTTGACTTAGAAGAACGAAACCCTAAAGTACTAAGTGCGGCTGA
ATTTCACGAAATTTTTCAAGGTGGTATGATTCTTATTACTTCACGAGCTTCTATTATGGGGCAATTGGCG
AAGTTTGATTTCACTTGGTTTATCCCCGCAGTAATTAAATACCGTAAAATTTTTGTAGAAACTATTATTG
TTTCTATTTTTTTGCAGCTTTTTGCACTAATTACTCCCTTATTTTTCCAAGTTGTGATGGATAAAGTTCT
TGTCCATCGTGGATTTTCTACACTTAATGTTATCACGGTTGCATTATCTGTAGTGGTTATCTTTGAAATT
GTATTAAGCGGTCTACGGACTTATATATTTTCCCATAGCACTAGCCGAATTGATGTAGAACTTGGTGCAA
AATTATTTCGTCACTTGTTAGCGTTACCTATTTCTTATTTCGAAAATAGACGTGTAGGTGACACAGTTGC
TCGAGTACGAGAATTGGATCAAATACGCAATTTTTTAACAGGTCAGGCACTTACCTCTGTATTAGATCTC
TTATTCTCTTTTATTTTCTTTGCAGTGATGTGGTATTACAGCCCAAAACTAACTATTGTGATTTTACTTT
CATTACCTTGTTATATCGCATGGTCAATATTTATTAGCCCAATATTACGTCGTCGTCTAGATGAAAAATT
TGCTCGTAATGCTGATAATCAATCTTTTTTAGTTGAATCTGTTTCTGCAATAGACACGATCAAGGCTCTT
GCTGTAACACCTCAAATGACAAATATTTGGGATAAACAGTTAGCAAGTTATGTATCAGCAGATTTTAGAG
TGACAGTATTGGCAACTATTGGACAGCAAGGTGTACAACTTATCCAAAAAACAGTAATGATAATTAATTT
ATGGTTAGGTGCACATTTAGTAATTTCAGGGGATCTTAGCATTGGACAATTAATTACTTTTAATATGCTT
TCAGGACAAGTTATTGCACCTGTAGTTCGTTTAGCACAATTGTGGCAAGACTTTCAACAAGTAGGAATTT
CTATTACACGATTGGGAGATGTCTTAAATTCACCTACAGAAAATTATCAAGGTAAGCTTTCACTACCAGA
AATCTTTGGGGATATCGCATTTAAACATATTCGCTTTCGCTATAAGCCCGATGCTCCAATCATTTTAGAT
GATGTAAATTTATCGGTTAAACAGGGGGAAGTTATTGGGATAGTAGGACGTTCAGGTTCAGGTAAAAGTA
CTCTCACTAAATTATTACAACGTTTTTATATTCCGGAAAATGGCCAAGTATTGATTGATGGTCACGATCT
TGCGCTTGCTGATCCTAATTGGTTACGTCGTCAAATTGGTGTTGTTTTACAAGATAATGTGTTATTAAAC
CGTAGTATTCGCGATAATATCGCACTCACTGATCCAAGCATGTCTATGGAACGTGTTATCTATGCGGCAA
AATTAGCAGGGGCACATGATTTTATTTCTGAATTACGTGAAGGTTACAATACTATTGTAGGAGAGCTTGG
TGCAGGCTTATCTGGTGGACAACGTCAACGGATTGCTATTGCACGAGCTTTAGTCAATAACCCTAGGATT
TTGATTTTTGATGAGGCGACAAGTGCATTAGATTATGAATCTGAACATATCATTATGCAAAATATGCAAA
AAATCTGCCATGGACGGACAGTAATCATTATTGCCCACCGTCTTTCTACAGTAAAAAATGCGGATCGCAT
TATTGTTATGGAAAAGGGACATATTGTAGAGCAAGGTAAACATAACCAATTACTGGAAAATGAAAATGGA
CTCTATTATTACCTCAACCAACTACAATCAAATTAA

Molecule Role : Virmugen
Molecule Role Annotation : An apxIIIB mutant, in combination with an apxIIID mutation, is highly attenuated in pigs and induces significant protection from challenge with wild type A. pleuropneumoniae. The mutant also was slightly attenuated in mice and induced protection in mice against challenge from the parent strain (Park et al., 2009).
Related Vaccine(s): Actinobacillus pleuropneumoniae apxIIIB and apxIIID double mutant vaccine

10. apxIIID

Gene Name : apxIIID
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serovar 2
NCBI Nucleotide GI : 470687
Other Database IDs : CDD:130902
Taxonomy ID : 34063
Gene Strand (Orientation) : ?
Protein Name : RTX toxin
Protein Note : type I secretion membrane fusion protein, HlyD family; TIGR01843

DNA Sequence : Show Sequence

>gb|L12145.1|ACNNON:6090-7523 Actinobacillus pleuropneumoniae (serotype 2) RTX toxin III (apxIII CABD) genes, complete cds
ATGAAGTTATGGATTCTAGGACTTGGGGAATTTTTTCAACGTTATCGTAATATTTGGCGTGAAATATGGA
AAATCCGCAAACAATTAGATACCCCAGCAAGACAAAAAGATGAAAACGAATTTTTGCCTCGGCATTTAGA
GTTAATTGAGACACCTATTTCAAAAAAGCCACGGCTGATCGCTTATTTGATAATGCTATTTCTATTTTTA
GCTATTGTAATTTCCATTATTAGTAAAGTAGAAATTGTTGCTAGTGCTACAGGTAAGTTGGTATTTAGTG
GACATAGTAAAGAAATAAAGCCTATTGAGAATGCTTTAGTAAAAGACATTTTTGTTAAAGATGGACAATT
TGTTGAAAAAGGACAATTATTATTAAATCTCACCGCACTTGGCTGCGATGCAGACAAACAAAAAACTAAA
GTATCGTTAGGATTGGAAAGATTAGATGGTTACCGATATAAGTCATTGTTATATAGCATTGAACACAATA
GATTACCTTTATTGGATTTTAACCAAGCTGATTTTGATTCTGTTCAGGAAGAAGATAAGACTGGCGCACG
TCATTTAATTACCGAACAATTTGAGACTTGGCAAAAACAAAAATATCAGAAGGAATTAGCGTATCAACGT
AAACAAGCTGAAAAACAAACAGTATTAGCAAATATCCGTAAATATGAAAGCGCTAGTCGTATTGAAAAGG
AGAAATTAAGTGATTTAAAAAAATTATATGATGTAAAGTCTATTTCTAAGCATGAGTTGTTAGCACAAGA
AAATAGATATGTTGAAGCTAGTAATGAATTGTCTGTTTATCAATCTCATCTCAAAGAAGTAGAAAGTGAC
TTGCTTAAAGCACAAGAAGATTTAAAGCTTGTTACTCAATTATTTAAGAGTGATATTTTGGAAAAACTAC
AGCAAAATATACAACGCGAAAAGCAGCTCACTTTAGAACTTGAGAAAAATGAACAACGTCAATTAGCCTC
TATCATTAGGGCGCCAGTATCAGGCACAGTCCAACAATTAAAAACTCATACTAAAGGTGGCGTAGTAACT
ACTGCAGAAACCTTAATGGTCATTGCTCCTGAGGATGACGTGTTGGAAGTAAGTGCTTTAATTCAAAACA
AAGATGTTGGTTTTGTTGAAATTGGACAGGAAGCAGTTATTAAAGTGGAAACTTTTCCCTACACAAGATA
TGGTTATCTCTATGGAAAAGTAAAAACTATTACTCTTGATGCTATTGAGCACCCTCAGCTTGGTTTAGTT
TTCAATTCTATTATTGAGATTAACAAGAAAACATTAACAGATGGTGATAAAGAAATTCAATTAGGTTCTG
GAATGAGCGTTATTGCAGAAATTAAAACAGGAGAACGCAGTGTTATCAGTTTCCTACTCAGTCCATTAGA
AGAATCTATTACTGAAAGTCTAAGAGAACGTTAA

Molecule Role : Virmugen
Molecule Role Annotation : An apxIIID mutant, in combination with an apxIIIB mutation, is highly attenuated in pigs and induces significant protection from challenge with wild type A. pleuropneumoniae. The mutant also was slightly attenuated in mice and induced protection in mice against challenge from the parent strain (Park et al., 2009).
Related Vaccine(s): Actinobacillus pleuropneumoniae apxIIIB and apxIIID double mutant vaccine

11. ApxIVA

Gene Name : ApxIVA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : 6671152
Other Database IDs : CDD:164328
CDD:116920
Taxonomy ID : 715
Gene Strand (Orientation) : ?
Protein Name : ApxIVA
Protein Length : 130
Protein Note : Peptidase M10 serralysin C terminal; cl12108

Protein Sequence : Show Sequence

>gi|6671152|gb|AAF23114.1| ApxIVA [Actinobacillus pleuropneumoniae]
DWGRNSVIDAGAGNDTVNGGYGDDTLIGGKGNDILKGSYGADTYLFSKGHGQDVIYEYSNSASSTSDIDT
LKFTDIGLSELWFSRENNDLIIKSLLSEDKVTVQNWYSHQDHKIENIRLSNEQMLVSTQV

Molecule Role : Virmugen
Molecule Role Annotation : A precisely defined DeltaapxIICDeltaapxIVA double-deletion mutant of A. pleuropneumoniae was constructed based on HB04C(-) by transconjugation and counterselection. The results demonstrated that the DeltaapxIICDeltaapxIVA double mutant strain was less virulent than HB04C(-). Despite attenuation of virulence, the DeltaapxIICDeltaapxIVA double mutant remains immunogenic and conferred a similar level of protective immunity to pigs against challenge with a lethal dose of a heterologous fully virulent standard serovar 1 strain of A. pleuropneumoniae (Liu et al., 2007).
Related Vaccine(s): Actinobacillus pleuropneumoniae apxIIC and apxIVA double deletion mutant vaccine

12. cpxD

Gene Name : cpxD
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serovar 2 str. S1536
NCBI Protein GI : AAB64442
Other Database IDs : CDD:132072
CDD:280687
Taxonomy ID : 715
Protein Name : CpxD
Protein pI : 7.5
Protein Weight : 38942.04
Protein Length : 452
Protein Note : J45 is a serotype 5a strain of Actinobacillus pleuropneumoniae

Protein Sequence : Show Sequence

>AAB64442.1 CpxD [Actinobacillus pleuropneumoniae]
MKLIKLRLLLSLGLVASLAACSSLPTSGPSHSAILEANSQNSDKPLPEVNLVELDNGLVQQLYQTQQSQQ
FSGFLGTAGGAGYAGAVNVGDVLEISIWEAPPAVLFGGTFSSEGQGSGHLTQLPAQMVNQNGTVTVPFVG
NIRVAGKTPEAIQSQIVGALQRKANQPQVLVKIANNNSADVTVIRQGNSIRMPLSANNERVLDAVAAVGG
TTENIEDVTVKLTRGSQVKTLAFETLISDPAQNIMLRAGDVVSLLNTPYSFTGLGAVGNNQQMKFSSKGI
TLAEAIGKMGGLIDTRSDPRGVFVFRHVPFSQLSLDQQTQWGAKGYGMGMDVPTVYRVNLLEPQSLFLLQ
RFPMQDKDIVYVSNAPLSEFQKFLRMIFSITSPVTSTTNAIRAY

Molecule Role : Protective antigen
Molecule Role Annotation : These data identify OM proteins(CpxD) that demonstrate immunogenicity and upregulation under conditions mimicking infection, providing emphasis on lipoproteins as an important class of antigens to exploit for vaccine development for A. pleuropneumoniae.(Chung et al., 2012)

13. fhuA

Gene Name : fhuA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : AAM69431
Other Database IDs : CDD:237595
CDD:238657
Taxonomy ID : 715
Protein Name : outer membrane ferric hydroxamate receptor FhuA
Protein pI : 7.47
Protein Weight : 72676.96
Protein Length : 800
Protein Note : ferrichrome receptor precursor protein; Provisional

Protein Sequence : Show Sequence

>AAM69431.1 outer membrane ferric hydroxamate receptor FhuA [Actinobacillus pleuropneumoniae]
MKKTFFYSTVASAVALAISPAIAQETAVLDEVSVVSSGSMYKMGEVPVHQAKSAVAISREDLDKQDVKKA
DEIGRYQAGFANQVFGNDTNTNWFRVRGEEVSQAVDGLPTFSYGFFTPYVKTFGLEAVEVTKGADSMTFG
AANSGGLINYVTKRAHRDQIGRGEFKTNFGSNNLYGFGADYTGKITDDENVRYRVVASLNHTDGEWKDTD
NKTVYIAPSLEWDISDRTRLSILTSYQKDSGTPSSNFYPQEGTLRALPDGSYYSRNVNFGDPVNNHEENK
QYSIGYELSHDFGNGLRANSSYRYSHVENNHRGGYIYPSAYAADWSAVAPSANGYNVSGQTVFNQGKAIS
HSTDNRISWDFKNDWLKNTVVVGTDYRHNKVDAQYSLYALGYTANLRDYRATWNQTGTPVGTDTHIKSRQ
LGFYLQNQARIADKYLLGFGIRHDRARQNEYTSDQTVKNNHTSYSGSLMYEGAYGLNPYFSYSESFRLPV
GLSGNQSLYDPNITRQYELGVKYLPTWLDGVITLAGFRAKDTGALVNNGTGATISSADPIYRKGFELQTD
VNLTENWNATLAYTYTKAESEAATGEKTRQSLIPTNTLAARTAYSFTDSVLNGLTVGAGVRYLGHSVTSK
GSLYSHVRLPSATVVDLMARYNINQNWLAQLNVDNVGNRKYVAACDYYCYYGAERKVNATVSYKF

Molecule Role : Protective antigen
Molecule Role Annotation : [FhuA and HgbA are conserved among all serotypes and biotypes of A. pleuropneumoniae and that HgbA, the receptor for porcine hemoglobin, may play a role in virulence.Ref4916:Shakarji et al., 2006]

14. hbpA

Gene Name : hbpA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : ABN75084
Other Database IDs : CDD:223818
CDD:173858
Taxonomy ID : 416269
Protein Name : Heme-binding protein A
Protein pI : 6.89
Protein Weight : 57811.6
Protein Length : 643
Protein Note : ABC-type transport system, periplasmic component [Amino acid transport and metabolism]; COG0747

Protein Sequence : Show Sequence

>ABN75084.1 Heme-binding protein A [Actinobacillus pleuropneumoniae serovar 5b str. L20]
MKLANLTKVSAAVLAVLALAACDDKNADGKTTAKPAAEKTFVNCVSRSPQYFSPALAMDGISYNASSQQV
YNRLVEFKRGSTEIEPALAESWDISEDGLTYTFHLRKGVKFHSNKEFTPSRDFNADDVVFSFNRQLDPNH
PYHTVSKATYPYFKAMKFPTLLKSVEKVDDHTVKFTLTKRDATFVSSLGMDFTSIYSAEYADAMLKAGKP
ETIDTTPIGTGPFAFTGYVLDQASRYVAYKDYWKGKADFDRLIFEIVPDATARYAKLQAGQCDLIDFPNA
TDIEKMKTDPKVQLLSQPGLNIAYVAFNTEKAPFDNVKVRQALNLAVDKKAIIDVVYQGAGIAAKNPLPP
TIWGYNDSLAESEFNIEKAKQLLAEAGYPNGFETELWVQPVVRASNPNPRRMSEIIQADWAKIGVKAKLV
TYEWGDYIKRTKAGELTAGTYGWSGDNGDPDNFLSPLFGSANVGNSNYARFNSPELDALLDKALGLSDKA
ERTKLYEQAQALLREQAPWINVAHSINFAPTSKRVQDYKQSPFGYTYLYGTKLAD

Molecule Role : Protective antigen
Molecule Role Annotation : Three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies(Chen et al., 2012)
Related Vaccine(s): A. pleuropneumoniae HbpA vaccine

15. hflX

Gene Name : hflX
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : ASU15836
Other Database IDs : CDD:330486
Taxonomy ID : 715
Protein Name : GTPase HflX
Protein pI : 6.07
Protein Weight : 42787.812
Protein Length : 470
Protein Note : GTP-binding GTPase Middle Region; cl25665

Protein Sequence : Show Sequence

>ASU15836.1 GTPase HflX [Actinobacillus pleuropneumoniae]
MEFQTLAESAGVEILATLTTSAPHIKYFVGQGKADEIAQAVKDLEATVVLVNHELSPSQTRNLQALCECR
VVDRTGLILDIFAQRARSHEGKLQVELAQLKHLATRLVRRLGNQDQQKGGAVGLRGPGETQLETDRRLIK
VRIQQLQNRLEKVNKQRSQNRKTRQKADIPTVSLVGYTNAGKSTLFNAITNAGVYAADQLFATLDPTLRR
MQIQDVGTTILADTVGFIRFLPHDLVSAFKSTLQETTEASLLLHVIDAADDRKNENIDAVNQVLDEIGAL
EVPTLLIYNKVDKLEGVMPHIERNDNGKPVAVYLSAQANQGIDLLYEAIRECLRNELVCEKVLLPATSGQ
IYTQFHLQRCIKNESFNQFGDRLVEVEVDLVQWNKWLKQFPELTEYVEFASWAED

Molecule Role : Protective antigen
Molecule Role Annotation : Six in vivo-induced (IVI) antigens-RnhB, GalU, GalT, Apl_1061, Apl_1166, and HflX used as vaccine candidates provide partial protection against Actinobacillus pleuropneumoniae infection in a mouse model, which could be used as potential vaccine candidates in piglets.(Zhang et al., 2016)

16. hypothetical protein APL_1061

Gene Name : hypothetical protein APL_1061
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : ABN74153
Other Database IDs : CDD:324543
Taxonomy ID : 416269
Protein Name : hypothetical protein
Protein pI : 9.35
Protein Weight : 21642.16
Protein Length : 298
Protein Note : Replication protein A, class 2b aminoacyl-tRNA synthetases, and related proteins with oligonucleotide/oligosaccharide (OB) fold; cl09930

Protein Sequence : Show Sequence

>ABN74153.1 hypothetical protein APL_1061 [Actinobacillus pleuropneumoniae serovar 5b str. L20]
MKKFMTMTSILALSSMALTSFANAEETTAQAQNNVQTEMPATAEKAVPVIGQQAVEFTRKAADQMMQGQG
RGQNFHSFHHNGKHPYDMMRMMAYHHPHQFGGYKPQGFIDQNAVAKDAKAALEAKDRSFVQLEGSISKQV
NDTEYTFVDSTGQIKIEVPPSLWRGLSVGPQDKVRIDGILDKQWEQPEIKVKNITRLK

Molecule Role : Protective antigen
Molecule Role Annotation : Six in vivo-induced (IVI) antigens-RnhB, GalU, GalT, Apl_1061, Apl_1166, and HflX used as vaccine candidates provide partial protection against Actinobacillus pleuropneumoniae infection in a mouse model, which could be used as potential vaccine candidates in piglets.(Zhang et al., 2016)

17. lip40

Gene Name : lip40
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : AKJ32477
Other Database IDs : CDD:295696
Taxonomy ID : 715
Protein Name : lipoprotein Lip40
Protein pI : 9.77
Protein Weight : 31139.75
Protein Length : 368
Protein Note : Transferrin binding protein-like solute binding protein; cl03152

Protein Sequence : Show Sequence

>AKJ32477.1 lipoprotein Lip40 [Actinobacillus pleuropneumoniae]
MKNITKFAVTLLAGLVITACGSKNHSIDIKPKSDKPKQEQPKQPQPKQDQPKQEQPKQEQPKKDQPKQDQ
PKQEQPKQDQPKDKTSGGVFIVEGVSKNLPQLTKEKLTDANLNSIKVDGIEIKFADATKAEGNWKVSPDN
SLVVCCDKYSSVRFGVYESKGKSYSFYNGNATAEMPTSGKFTYTGDAYLLASVVGNGAESIGTSKFEADF
GTKKLTGTLTFDKLKDSKNVDIDSKISGNSFTGKATFDSFKGTDAIVEGKFYGENAKELAGAFDSAKEKG
AKLGDKSWGGVFGAKQQK

Molecule Role : Protective antigen
Molecule Role Annotation : Recombinant Lip40 (rLip40) produced in Escherichia coli BL21(DE3) was specifically recognized by porcine convalescent serum directed against A. pleuropneumoniae. Lip40 also protected 75% of mice from fatal virulent A. pleuropneumoniae infection.(Hu et al., 2015)

18. omlA

Gene Name : omlA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serovar 2 str. S1536
NCBI Protein GI : CAA73336
Other Database IDs : CDD:295696
GOA:O31239
InterPro: IPR001677
UniProtKB/TrEMBL: O31239
Taxonomy ID : 871925
Protein Name : OmlA
Protein pI : 7.48
Protein Weight : 23674.62
Protein Length : 306
Protein Note : Transferrin binding protein-like solute binding protein; cl03152

Protein Sequence : Show Sequence

>CAA73336.1 omlA, partial [Actinobacillus pleuropneumoniae serovar 2 str. S1536]
KDINSGIINNADVVLNLKIDEKDQIKIVLDKSEINRDSLKVTNAIPTQDIKTLKDSSGKLLGYYGYMQLS
QVRQDESYSTDSLNLSNYYLLSMNEQEKTRPSKSLTYKGTMIYGYSSVANNKLEAEVKAQYDHSSKKLSM
QVFGQDNEHWRLAEASGINNVKLPASKLRDVIVSDKGDINGLLYLEDSTPSKFTPNANFSGGFFGKNGEV
LAGKAESIKG

Molecule Role : Protective antigen
Molecule Role Annotation : CpxD) as well as surface antigens TbpA, TbpB, and OmlA. These data identify OM proteins that demonstrate immunogenicity and upregulation under conditions mimicking infection, providing emphasis on lipoproteins as an important class of antigens to exploit for vaccine development for A. pleuropneumoniae.(Chung et al., 2012)

19. ompA

Gene Name : ompA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : ABV82725
Other Database IDs : ATCC:27088
CDD:332966
CDD:143586
Taxonomy ID : 715
Protein Name : OmpA
Protein pI : 5.45
Protein Weight : 26230.02
Protein Length : 286
Protein Note : Peptidoglycan binding domains similar to the C-terminal domain of outer-membrane protein OmpA; cl28145

Protein Sequence : Show Sequence

>ABV82725.1 OmpA [Actinobacillus pleuropneumoniae]
MQIDFSKLKLQQQESEDSQWLPVSDLMSGLMILFLFIAVSFILNAKRVADNYQDNQEKIYQALQTEFSPK
LKDWKAKIDKDTLTFIFTDPEVLFETGRSDLNAPFKKILDDFFPRYMKVVDNYKTSISEIRIEGHTSTEW
DHKSSDDMAYFLNMQLSQDRTRSVLIYLYQLENIAQYRDWIKSNLSAVGLSSSKTIKNTQGIEDKEASKR
VTFRIITNAEEQLRKLSEIK

Molecule Role : Protective antigen
Molecule Role Annotation : The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.(Hur et al., 2016)
Related Vaccine(s): mixture of Salmonella strains delivering ApxIA, ApxIIA, ApxIIIA and OmpA of A. pleuropneumoniae

20. ompW

Gene Name : ompW
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : ASU14913
Other Database IDs : CDD:328747
Taxonomy ID : 715
Protein Name : Outer membrane protein W
Protein pI : 8.7
Protein Weight : 21467.67
Protein Length : 291
Protein Note : Porin superfamily. These outer membrane channels share a beta-barrel structure that differ in strand and shear number. Classical (gram-negative) porins are non-specific channels for small hydrophillic molecules and form 16 beta-stranded barrels (16,20)...; cl21487

Protein Sequence : Show Sequence

>ASU14913.1 Outer membrane protein W [Actinobacillus pleuropneumoniae]
MKKAVLAAVLGGALLADSAMAHQAGDVIFRAGAIGVIANSSSDYQTGADVNLDVNNNIQLGLTGTYMLSD
NLGLELLAATPFSHKITGKLGATDLGEVAKVKHLPPSLYLQYYFFDSNATVRPYVGAGLNYTRFFSAESL
KPQLVQNLRVKKHSVAPIANLGVDVKLTDNLSFNAAAWYTRIKTTADYDVPGLGHVSTPITLDPVVLFSG
ISYKF

Molecule Role : Protective antigen
Molecule Role Annotation : APJL_0126, HbpA and OmpW were further tested in the natural host (swine) by homologous and heterologous challenges., showing that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae.(Chen et al., 2012)
Related Vaccine(s): A. pleuropneumoniae OmpW vaccine

21. potD2

Gene Name : potD2
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : ABN73472
Other Database IDs : CDD:330233
Taxonomy ID : 416269
Protein Name : spermidine/putrescine-binding periplasmic protein 1 precursor
Protein pI : 4.96
Protein Weight : 37764.89
Protein Length : 495
Protein Note : The substrate binding domain of LysR-type transcriptional regulators (LTTRs), a member of the type 2 periplasmic binding fold protein superfamily; cl25412

Protein Sequence : Show Sequence

>ABN73472.1 spermidine/putrescine-binding periplasmic protein 1 precursor [Actinobacillus pleuropneumoniae serovar 5b str. L20]
MKKLAGLFAAGLATVALTACNEEKPKAAEAAAQPAAAGTVHLYTWTEYVPEGLLDEFTKQTGIKVEVSSL
ESNETMYAKLKLQGKDGGYDVIAPSNYFVSKMAKEGMLAELDHAKLPVIKELNQDWLNKPYDQGNKYSLP
QLLGAPGIAFNSNDYKGDAFTSWGDLWKPEFANKVQLLDDAREVFNIALLKLGKNPNTTNPEEIKAAYEE
LRKLRPNVLSFTSDNPANSFIAGEVSVGQLWNGSVRIAKKEQAPVNMVFPKEGPVLWVDTLAIPANAKNK
ENAHKLINYLLSAPVAEKLTLEIGYPTSNVEALKTLPKEITEDPAIYPTADVLKAAQWQDDVGNAIELYE
KYYQELKAAK

Molecule Role : Protective antigen
Molecule Role Annotation : Immunoblots of iron-restricted profiles detected PotD2, heme-binding protein A (HbpA), and capsule polysaccharide export protein (CpxD) as well as surface antigens TbpA, TbpB, and OmlA. These data identify OM proteins that demonstrate immunogenicity and upregulation under conditions mimicking infection.(Chung et al., 2012)

22. tfbA

Gene Name : tfbA
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae
NCBI Protein GI : AAA21929
Other Database IDs : CDD:279621
Taxonomy ID : 715
Protein Name : transferrin-binding protein
Protein pI : 7.6
Protein Weight : 56362.89
Protein Length : 630
Protein Note : Transferrin binding protein-like solute binding protein; pfam01298

Protein Sequence : Show Sequence

>AAA21929.1 transferrin-binding protein [Actinobacillus pleuropneumoniae]
MHFKLNPYALAFTSLFLVACSGGKGSFDLEDVRPNKTTGVSKEEYKDVETAKKEKEQLGELMEPALGYVV
KVPVSSFENKKVDISDIEVITNGNLDDVPYKANSSKYNYPDIKTKDSSLQYVRSGYVIDGEHSGSNEKGY
VYYKGNSPAKELPVNQLLTYTGSWDFTSNANLNNEEGRPNYLNDDYYTKFIGKRVGLVSGDAKPAKHKYT
SQFEVDFATKKMTGKLSDKEKTIYTVNADIRGNRFTGAATASDKNKGKGESYNFFSADSQSLEGGFYGPK
AEEMAGKFVANDKSLFAVFSAKHNGSNVNTVRIIDASKIDLTNFSISELNNFGDASVLIIDGKKIKLAGS
GFTNKHTIEINGKTMVAVACCSNLEYMKFGQLWQQAEGGKPENNSLFLQGERTATDKMPKGGNYKYIGTW
DAQVSKENNWVATADDDRKAGYRTEFDVDFGNKNLSGKLFDKNGVNPVFTVDAKIDGNGFTGKAKTSDEG
FALDSGSSRYENVKFNDVAVSGGFYGPTAAELGGQFHHKSENGSVGAVFGAKQQVKK

Molecule Role : Protective antigen
Molecule Role Annotation : Immunoblots of iron-restricted profiles detected PotD2, heme-binding protein A (HbpA), and capsule polysaccharide export protein (CpxD) as well as surface antigens TbpA, TbpB, and OmlA. These data identify OM proteins that demonstrate immunogenicity and upregulation under conditions mimicking infection.(Chung et al., 2012)

23. tonB2

Gene Name : tonB2
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serovar 2 str. S1537
NCBI Protein GI : AAR95695
Other Database IDs : CDD:330347
CDD:281534
Taxonomy ID : 715
Protein Name : TonB2
Protein pI : 10.26
Protein Weight : 28571.46
Protein Length : 343
Protein Note : TonB N-terminal region; cl25526

Protein Sequence : Show Sequence

>AAR95695.1 TonB2 [Actinobacillus pleuropneumoniae]
MKKKHSRIGLTGSILIHTAIFGGLASMVTHSHSDDLPQEETMSMELVAALLEQPQVAVAQEEPAPPEPEK
VEVEPEPEPEAEAIPELKPQPKPKEKPKEKPKEKPKPKEPPKPKEKEKPKKEKVKDKPIKALEKGPEAKQ
GIVAKAIPNAVQGTQLRAGIPNGKPEGNPNGLSANGSQNGAVGGSGSGASGSEIGAYKAALQRALQRRAN
NAYPTREKMMRKTGVVTIGFTVSSSGELINVKVLNSSGNGNLDNAAVKAAQSTKVSPPPAGFPSNVTVPV
KFSIE

Molecule Role : Protective antigen
Molecule Role Annotation : The survival rate of the TonB2-vaccinated mice was significant higher than that of the mice given recombinant GST or adjuvant alone.(Liu et al., 2011)
Related Vaccine(s): A. pleuropneumoniae TonB2 vaccine

24. ureC

Gene Name : ureC
Sequence Strain (Species/Organism) : Actinobacillus pleuropneumoniae serovar 2
NCBI Protein GI : 303253439
Other Database IDs : CDD:183894
CDD:30031
Taxonomy ID : 754254
Gene Strand (Orientation) : ?
Protein Name : urease subunit alpha
Protein Length : 572
Protein Note : urease subunit alpha; Reviewed; PRK13207

Protein Sequence : Show Sequence

>gi|303253439|ref|ZP_07339581.1| urease subunit alpha [Actinobacillus pleuropneumoniae serovar 2 str. 4226]
MALIIPRSQYVATYGPTVGDKVRLGDTDLWATIEQDFLTKGDECKFGGGKSVRDGMAQSSTATRDNPNVL
DFALTNVMIIDAKLGIIKADIGIRDGRIVGIGQAGNPDTMDNVTPNMIIGASTEVHNGAHLIATAGGIDT
HIHWICPQQAQHAIENGITTMIGGGSGPADGTHATTCTPGKFNIERMFQACEALPVNIGFFGKGNCSMLE
PLKEQVVAGALGLKIHEDWGATPAVIDAALKVADEMDVQVAIHTDTLNESGFLEDTMKAINGRVIHTFHT
EGAGGGHAPDIIKAAMYPNVLPASTNPTRPFTVNTIDEHLDMLMVCHHLDKRVPEDVAFADSRIRPETIA
AEDILHDMGVFSIMSSDSQAMGRVGEVVTRTWQTADKMKAQRGALGDEGNDNFRIKRYIAKYTINPAIAH
GICQYVGSLEVGKLADIVLWKPQFFGVKPEFVMKKGFISFAKMGDPNASIPTPQPVFYRPMFGANAKANT
ESAVYFVSQASVDANIKAQYGIQKETLAVKGCRDVGKKDLVHNNATPEITVDPERYEVRVDGEHITCEPA
TKVPLAQRYFLF

Molecule Role : Virmugen
Molecule Role Annotation : Deletions were introduced into the ureC and apxIIA genes of an Actinobacillus pleuropneumoniae serotype 2 strain by homologous recombination and counterselection. The double-mutant contains no foreign DNA, is highly attenuated, protects pigs from homologous challenge upon a single aerosol application (Tonpitak et al., 2002).
Related Vaccine(s): Actinobacillus pleuropneumoniae ureC and apxIIA double mutant deletion vaccine

III. Vaccine Related Host Genes

1. A2M

Gene Name : A2M
Sequence Strain (Species/Organism) : Homo sapiens
NCBI Gene ID : 2
NCBI Protein GI : 66932947
Genbank Accession : ABBA01012257
Protein Accession : NP_000005
Taxonomy ID : 9606
Chromosome No : 12
Gene Starting Position : 9067707
Gene Ending Position : 9115961
Gene Strand (Orientation) : -
Protein Name : transcript variant X1
Protein pI : 6.39
Protein Weight : 149502.37
Protein Length : 1474
Protein Note : Also known as A2MD; CPAMD5; FWP007; S863-7

DNA Sequence : Show Sequence

>gi|568815586:9067707-9115961 Homo sapiens chromosome 12, GRCh38 Primary Assembly
AGACATTGACCAGAAAAAGTGTTTATTCATCAAGTCTTTAAAGATACAAAAACACGTGTCTTCTGTGGAG
CTCTGAGAACAGGACTCCAGCAAAGCACTTTTCAGCCTTGTGGTCTTCAAGCATTTCCAAGATCTGTGAC
ATTGGAAAGAAAAAAAATTAAGACAGATTTGGGTCTCCATGAGCAGAGAGTATTCTTTCCCTTAGTTCTG
GGTAGCATAGTGCCCAAGGAAACCTAATCAGTACAGTGGGAAACCAAATCTATTCCAAATCATTACCCAT
AAGCAATCCTATGGACTCTCTGAGGTTTGACAGAGTCAGCGGCCCTCTCCAATAAATGTGTTTTTCTATA
ATAATGTGCAGTGTGAGTAATTTGATGTTTTTGACAAATATTTACCCAGCGTTTTATGAAGGAGAAGGTT
TGGGGGGCAAGCTGAAGGAGCTCTGACTGCCTTTTGGAGGAGTGTGAGTGGCTTACCTTTGCTGCAAGGA
GCATTGTACTCAGCAATTGCAAACTCATCTGAAAAAAAAAAAACCAACAAAAAACCAGAAATCATTACAT
GAAGTGAGAAAGAAAGCAAACATCTGTGGGATACAGGCCAAGGAAGGAGTTTGTTGTGGGAAGAACAGTA
TTGTACCAGAAACATAAGCATCATTCATCTGATGTGTTGCTTGCTACCTTATATTCTCCTTTCAAATATA
GTGTTTTATATATTCTTTTATCCCAAACTCCTGAAGGACTCTTCAGATGTTCTACTTACTTAAATCTCAT
ATTGTCATACAGTCCATTTATCTGATGAAAAGGGAACTAAATATCCCACAGGTGTTTTGTATTAGTAGTT
GATAAATTTATAATGTAGGTTGTTTCTATAATGTATGTATAAGAGACAAAAAGAGGGGCATCAGACTTGA
TGGAGACAAAATGAAGTGATAATGTAATTACTTAATGTAATAAATAACCCCAACACATCTCCTAAACCTG
AATTTCTGTGATCAGGAATTAAATATTTCTACGTGAAAATCACTCTCACTCACCCGTCTCGTAGTAATCA
TAGACTTTCACTATGGCTGGTTTCAGATCTCTTACTGGGACATCTTGCAGAACCGTGAAGAACAAGCTCA
GTGTCTGATTTGACACCTGGAAAGCAAAAGTCAATTAAATGACCTTTCAGGAAGCTTTCTTCTCTCTTTG
AATTAGTTTAAGTATTCACCTGTTTTTTGGGGGAAAAGCTTTATTATCCTACAGCACACTATAGGGTCCT
TAATTAAATTGTGCAGAAATCTCTCAGAGGGGATGATAAATTCTCCAGATTATTTCTTAAATAACTAACA
TAACGCATATACCTCTGTCAATGCCAATACATAGCTCTGTTCATGGGGGTAAATGATATATACTTTTTAT
TGGATGACTAACTGTGTTCATTTTTTAATATCCAGAGATTTGGTATAGTTTGACTTCTCTGTCTTGCAGG
AATACTTGCGTAGACTCAAAGAGGCATCTAAAAGGTTGATCTTCCCAGGCTTAAGTTTCATAAAATTTGT
AAACTATAATTCCCATCAACTTATGCATGAACAAACTCTCCTACCACACATATCTATAAAATCAGATTGG
TTTACTGGTGAACTGGTCTTATTATTTTATGGTTCAAGTCCTTGTGGAGACTGACAGTTTTTTTTCCCTT
TCATATTGTTGTTGAGTATGTTGATAATTAACTAATAATTGACTAATCACAAGGGCTACTTCCTTATATT
ACTGGGTATCCAAAAAACTTGTCAACATAATAAACACATTTTGTGAAGATTTCTTGCTTATGGGATTTTA
GGAATATTCATATCCCAAGATCATAATAAGCCATTTCTACCTGTAATCCCTGGTGAAATATAAATAAAGG
AGAGAAGAACATTCTTTTAGAGTTAACATTAGAATTCTCAAATTTCTAGCATGGAAGTGATGTTTCTAAA
ATGCATTTACCTTCCCAGATGTTCCCTTAGAGGATTATTATCTACGTTTTTTTGCAAATAGACTGGAAGT
TCTCTTACCTTATCAAGGTAAATCAAGACATGGTTGCTGCTGACTTCTGTCCGGCTCACATGGTTAGATC
TTTCAAGCTGAAGAAAATTGAAATACCACAAATGTTAATAAATAGATGAAACCCCTGGGGGATCCAGAGA
AAAAATCTTTGTATTGCCAAAATAACCCTGAGGGTAGAATTCTTCAAATGCTTTTTGTAAGGAAATATAT
AATGTAATACAATTAAAAATGAAAGGCATAAAGGGTTTACTATTAGTATAACACACGACTAATGTGTAAA
GTTATTTATCTGAAGAAAAGACAGCTAAGTATCCTAAACTTGGTAGTTACTCATATTTCAAAGTTCAATT
CAGTTTCTATTTCTTCATAAGGAGTTTTTTTCCTGTTTTGCTTGCTCTATTTTTCTTTTAACTTCTGTAA
TACTTATAGTTTATGCCAATCAGTCATTTTCATATTTTTCACTGGTTCGTGTTCATATCTTTTATCTTCT
TAGCAAAATTCTAAGCTAAGAAGAAATTGAAAAGCAGGAACCTGCTGACAATCTTTTTCTTGTAGTCATG
GGTCCTAGCACAGTGCTCTGCACATGGTCAGCATTCATACAAACACATGTGATTATATTTCTGAGCTGGA
AAAAGGATAAGGCTTTGATAGAGATTGACTTTAATAGTATTTTGATATTAGTATTGTCTTATGCTGGGGA
TACATACATCATTAAATAAAATAGGGCAGTCTGGGGTTATGATAAACCTACCATTTTCACTGTTGGCTTC
AGGGGAATGAAGCCAGAGACCATCTTCACATCAACGATCGCCATGTTGGAGGCAGAGCGGCTCCCTGTGT
AACTGAGGATCCAGGGGAGGAAAGGATTAGGGTTTTCTGTGTTTTTAAATATTTTCTTCTTCTATGTCCA
TGTTAAGCATTCCACAGCTCTAAAAGGTACACGTAAGTCTTCCCAAATATCTTATCCCAGTGGTTTGTAA
AAGTGGTGTGCGTAGAATTTTTAGGAAGCCTGTTAAAGCCACAGAGACCAGGCCCTACTCTAGACCTGAT
GAATCAGAATGTCTAGTGTATGGGGGCTGAGGATCTGCATTTTTTTTTTTTGATGGAGTTTTTCACTCTT
CTTGCCCAGGCTGGAGTGCAATGGCATGATTTCGGCTCACCGCAACCTCCGCCTCCTGGGTTCAAGTGAT
TCTCCTGCCTCAGCCTCCCGAGTAGCTGGGATTACAGGCATGCACCACCACGTCCGACTAATTTTGTATT
TTTAGTACAGACGGGGTTTCTCCATGTTGGTCAGGCTGGTCTTGAACTCCCGACCTAAGGTAATCTGCCC
GCCTTGGCCTCCCAAAGTGCTGAGATTACAGGCGTGAGCCACCACGCCCGGCTGAGGATCTGCATTTTAA
GAAAGCTCTACAAGTGATGCACAGGCTGTTTGTGACCTCTAATCTATGCCAGTTATTTTATTTATTTGTT
TACTTTTATTTTCTTTCAGCTGACAAAATGATGTATATTATGAATAATAAATTTCAGTCTACATTATTTA
CAAAAACAACAATAATTTATAATGTTTACTTAAACACTGGCTTTCAACAAAACACTTAGAAACACCTAGC
GTCTTGTCCCCGAGAGTTTGCATCCGAAATTTGGACTGCTTAATTTATTTTTTGGCATATATATACACCA
AATTAAATGAAAAAAATATATATATATATACTTAACTTTTAGGTTCAGGCGTACACATGCAGGTTTGTTA
TATAGGTAAACTCGTGTCATGGGGGTTTGGTGTACAGATTACTTTATCACTTGGGTACTAAATTTTGCAC
TGAATTGTTGTTTTTTTCTGATCTTCTCCCTCCTCCCATCCTTAACCCTCAAGTAGGCTCTGGTGTCTGT
TGTTCTCCTTTTTGTGTCCATATGTTCTCATCATTTAGCTCCCACTTACAAATGAGAACATGCAGTGTTT
GGTTTTCCATTCCTGTGCTAGTTTGCCAAGGATAATGACCTCCATCTCCATCCATGTTCCTGCAAAGGTC
ATGATCTCATTCTTTTTGATGTGTGCCAGTTATTTGTTACATGTATTTTGTCCTAACTTTTTTCCTGAAT
AGTATCTCCAACCAAGTAATAATATGTTTGTGGAGAGAGAGTTTTTTATCAGATCTGCAGCTATTTAAAT
ATTGATGCATATAAGTGTATCTTCCCCCCAAATTAATTATATCATATATAACCTGAGATTTATTATTGCC
AGTAGGAATTCTAACTAAGGAGTCACTACTTCCTTCTATTCAAACTTTTCAATAATTCTTCATCTCTATC
TTCAATAAAGCAAGAATAATATAGGATTTCATTACATAACAAGGAATTCAGGTCAGAGGCAATGGGTAAT
ATTTACTTAGTTGTTATTGAGGGAAATTATTACCCTTTAAACAATGAGGTTGCACAATAGTAGATCCTGG
ATGGACAATGTAAACCCCATCATTGAGAAATTATATCAACTTAAGAGAATACATTGCATTTTTTGTGAAT
AGTGCAAATATCTACTGTTGCACTGCTTTACTTAAAGAGGAGTTCCCGAAAGAAGACTGGTGGTTATTCT
TAGGATTAGGTGATAGAGTCAGAAGGTCTTACCTGACACTTAGGGAGATTTGGAAGCTGGTGTGGGCTTT
GGGTTCATCACAAGTTTGAGGCAGAGTCTGCACTCCTAAAGCAAAGGGGAACTCTTCCTTTTCTGGGAGA
ATATTGTATTTCAAGGATGTCTATAGAACATCAAAGACAAAATCAGTTTTTTGCCCTTTCCCAGAATTCC
TGTCCACGTCCCTAACCCTTTCTCTGATCTGTCCCATTGTTTTCTGAGTTAGGACTTCTCAGAGAGAACA
GCTGCTGTCCTCATCTGTCCTGTCCTCACCTGCCCAAGAGTCTCACCTGGAGGTAGACACATCCTTCTCC
TGTCACTTTCATGCTGTATTCCCCAGGCAGCTCTGGCAATGAGACCTGCTGCAGTAACAGGCGGTTGTTG
TTGTCCACTTGGAATTTGCTGGAAAATGTCCCTGAAGACTGGATAGTCACCTGTGCAGCCTTCCCAGTCC
TGGTAAATGTGGCTGCTCCATATTTGGACAGAGCATGGAGAGCCACCACTGTGTCCTGTTAGAGACAGAT
GAGTGAGAGAACCCATTGGGCATTATAAGGCTTTGAGGGCTGAGATATTTTTCAAAGACCCATGTGAGGG
ACTTTGATTTCCTACTTCCCTCACTACTTAAATATAGGAGCTGTAATTTCAAGATTGATTATAATCTTTA
GATAGTTGAAGAACCATAACATTCACATATCTACCTTGGACTGTATGCCCTACATGTTTATTTTATTTAT
CAGAAAATTGATCCTTTTCTCTCTGTAAGTATATGTGGGACATGGAATGTGGAAAACATGTGAATGGCAA
TCAGTTATTGGCATCAGCTATTTGCTAACATGTCTTTCTTGACAACTATGCTCATATCTGCCACCACTCA
AGCAAAGTTCAGTCTGGCTCTCTCCCATATTAAACTTTGCTCAGTTGCTGAGGTCAGTGTCCTGGAGAGA
ACCCAAGGTTCTTTGCAGCCATGAGCAGAGTCATGCTTCAGTTTCTCCAAAAGAAATAAAAGATGAGTAT
TATAATTATCTTCTGGATTTAATGACATTTTTATTTGGCTTTCCCTTTTTATTGGATGATTTCCTGTTCC
CAGTGAATGTCTGCTGGTATGTATCCTCAACAACATTAAACCTGCTTGGCCTCCTTCAAATAATATGTTT
CTAATAAATGAATGATAACCTTTAACAAAATTACTTAGTTTTTTTCATTCATATGATAAAAGATTAATAC
AATGGAAATAGGATGGAATGCCATTTTGTCACATTTTTTCCGTTTTAGGGTATATAAGCAAACATCCGAA
TTCTCTGAAGATAAAACTTTCTGCTGTGTACATATCAATGAATTGTTCAGATACATGGTTATATAGCTAG
ATTTAGGAGGTTGGATGAATAAAGACAGTTCTTTATGCTCCTGATGAATAAATGTTTGTGTATTAAGAGG
TGAATAGGGGGCTGGACGCAGTGGCTCACACCTATAATCCTAGCACTTTGTGAGGCCAAGGCGGATGGAT
TGCCTGAGCTCAGGACTTCGAGATCAGCCTGGGCAACATGGCAAAACCTCGTCTCTACTAAAAATACAAA
AATTAGCCAGGCATGATTGCACATGACTGTAATCCTAGATACTTGGGAGGCTGAGGCACTAGAATCGCTT
GAACCTGGGAGATGGAGGTTGCAGTGAGCCGAGATTGCACCACTGCATTCCAGCCTAGGTGACAGAGCAA
GACTCTGTCTTAAAAAAAAAAAAAAAAAAAAGGTGAATAGGGGAAGCACAAAATGTGTAGTTTTGAGAAA
AGCCTATTAAAGGGGACCTAAGAATGGAGAGATTTGCGAGGAGAGGTTGTTGGATTTTGAGTAGAGTTCC
TTTGAACAGTTTGAAAGAGACCCTAGAGCTTTCAGGAGAATGGCAGGAGACATCTCCTTCATTCTGCTGG
TGCTCCACTGCTGCTTGAGGAAGGCAGTGTTGTTATGGGAAATAGGAGATGGATAATAACACAGCGATGG
GGTGCCGGGATTCTGAGCATTTCCTTTTGGCCCTCTTTGACTTTGATTTGCTTTTATTTCCATTATCCTT
GGATACTGAAAACTTTTCCTCATTTCAAGTTACTGTCATCTGTATTTTTTTCTTCTTGGATGTGTTTGTT
TCTTTTTCATTCAAATCTTTTGCTACCTGAAGGTGAAATAAAAGGTTTTGGCAAATCACCAACCTGGGTG
GAGGAGAAACCGCCCTGGGCATTCTGCTGCTTCGTGATCCACTTCACGATGTTGGTTGCAGAGGTCAGGT
CCTCCGAGGTTGGGGCTGGCTGGGCCGTGAGATAAGCGAGGAGCACATAGGATGTCATCTCCACCTCAGC
AGAGGGAGCCTGGGGTTCGTAAAAATGCCCCACTGGTGCCTTGGGTTTCTGAGGGCGCTCCCAATGGACA
GAGTTGTCTTAAAGATGAGAAAAAGATATTTATAAGTGCCTACATATTTATATTTAATTCAAGGTGAAAG
TACCCAAGCCAGTGCTGAAATGAGAATTGCATGCCCATTATAATCCCCTGTACTGTATGTAGATGCTTTT
CCCTTCATGTAAATCTGAATTTGGTGTGTTTTAGCCCAGCTAAGGCAGATATTGATGCTGGAGTCAGAAG
CCTATGCCTATCTATGTTTTCAAATCGTTGCTATAGTCGGGTTGGTGGGAGAAAGAAATGGCACAGCAGT
TGTCTCATTGAGTCTGGCTATTTCCTATTTATGATGTTATATTAGACTATAGCTGGAGTTTGTTACATTT
CCTATAAAGTGTGTCTTTATCAGTTTCTTGTGAGGATCACAGATCACATGAAATAGTAGAGTTTCTACTC
ATTAAATTGAAAAAAAAAATACAGTAATCCTTGAAATACCAAAGGCTGACATGGATGTGAAACAATGGGA
ACCAATATACACTGCTGTGGGAAGCCAACTGCTCTTTGGCAATATTCAGCAATGGGGAAGATGTGCTTAG
CCCACTAATCAGTCATTATGCTTCTCAAAGCATAATTTGGAGAAACACAGATGCACAAGAAAACAGGCAC
ATGAGTATTCATTGCAGCATTTTTTTTAATAGCAAAACATAAAAAAAATCCATGAGGAGAAACTCGATGT
GTAAATTATGACTAATTTATAGACTGTAATATATTATGCAGCAGTGAAAATTAATGAGCTGACTCTGCAC
ATACTTGTATAGGGGTCTTCATCAACATAGTGTTGAACTTAGAAAATAAAAAGCAGACAAACAAAAAACT
AAGCTGCTGAAATATTCAAAAATGTTTCTCTTGTTTCTTGAATAAGAGAGAAATAAAAATCTTGTTTCTC
TCAAGATGAAACACATGTGAAGATTCTAAATATTAGTTAGGGATACATATGCAGCAAAAATATAAGGAAA
TCCATGGAATTGTAACGACAAATTCAGGATAATGATTGCCTCTGGAGGTGGTAGTGATACACAAGGGATT
TATTTTTCCCATGTCGGTAATTTTCTATTTCTTAATCTATGAGAGAGTTGTACAGTGTTTTCTAGTTATA
GCTTATGCCCTTTTGTATATCTATTATAAAATATTTCTCAATACATTTTAAGAAGAATTAATGGCTGTCA
AAGGAAAAAGGTAGACTGTTTTAATGGACATCTTGTGATTTGCATTTTATTTTCTATTTCTTCAACCGCT
CATATAGACCATGGTATATGTAGAAGTACTGTGTGAATATGAGTAGATTGGTCAACATTATTGGTCTTAT
GAAATGGGCTTAAAATACCAGAATTCATTCAAGGAGTTACTTCCATGATTATTTTCTTATGTTTAAGGTT
ATATAATGTACCAGGTAAGGGTTGGGCATATATTGAGAACTGATATGTTAATTGTAATAACTAGTACTTT
TATAGGATTTGCTATGTGACATGTACTCTACTAAGTGTTTTACGTGTACCAATTCATTTATTACAACAGC
TCTGTGAGGTAAATACTATTATTATCCCCATTTTACTGATGAAGGAACTGAAACACAAGGAAGTTAATGA
CTTTCCCAAGCTCACATAGGTAGCACATTTTGGAGCTAGTCTCCAGAGAATGCTCTTCTTACCAGCATAC
TATAGAGATGGTCCCTGACTTACAATGGTCCCACTTAAGATTTTTTAGACTTTACAATGAGTTTGTCAGG
ATATAACCCCATCGTAATTGAGAAGCATCTGCACGGCCTCTTGTCTTCTGATTTCTGATTTGATTAAGAA
ATCCTAGATTTTATAAGATGCAATATGGACAAAATATATATGATATATAGAAAAGAAGAGAGGAGACAGG
GATCACAGGAGGTAGGAGTGAGGGATTTTTGCCATGCAGTTCTTGATACAGAGGATGGGCCAGGAGAAGG
ATCTCAGGTGTGCTCTCACCTTTCTTCACAGCTTCCTCATTAAGTGACTTGAGTACTTCCTTCCTCTTGT
CCTGGTTACCTGCCAGGGCAAAAGCATAGGCCAGCAGTGCTTTGGTATATACATGGCTGCCATGGTCCCC
TTCTTGTGCTGTCTTCCAGGCTGACTCCAGGCAAAACAGGGCATTGCGGACAACAGGGTGCTGTGAAGGC
AGAACAAGAAGGGAACTAAGCTATGTAAACAGGCATATTAGCATTCCCAGGCAAATACACGGATCACAGC
ACAGAAGTTTTTCAAACGCATTTTTCCAACGATTCCTCATTCTTATCAATAGATATAATATTATTTTTAT
CTGTTATTCTCACATTCAAAAGATACATCTTTAAGATTCTTTTTTGAGTGGTGGTGGTAAATAGCCTAGG
GGAATTACTGGGAAAATTTAAACCTTTCTTAATGGGCTGACCAAATTCTCTGTAGATCTGGGAAGCACTG
GCATTGCATAGAAAGAAAGCTGATGCTTTGCTTTTAATAGGATAGTATTTCAGACAGCAGGTCAGCAGTT
TCATTGCATCCAGAACTCTCCTTCAGCAGAGGAATGGGGTGGTACCTACAGTGACTGTGAGAGGAATCTC
CAGAAGGGCGATGGTGATATAGGCGGAGAGGGTCACTTCATCTTCTACTCCTCCCTGTGAATACGAGAGA
GAGATCTGAATAATTCAACTTCTGAGAATGCTATTGATTAGTTCTTTCTATTCTGCTGTGTCATGGAATT
CATCCTTACCCATATCCATCCCTATAGGGCAAAGTATCACAATCAACTTTTGTTCTATCCCCTCTTTTTT
GGTGCCATCCAGGTTTTATTTTCCTCTGAGGCTTTCCCTTAGAATTTTTCACATTATCACTTCCTATCCT
CATCCTTGCAGATATCATAATGGACAAATCAAAACTAGCTCCAGAATGATTCACCTTTATGGCATTGTTG
AGCAGTGACCCAGAGCTCCTGAAACAGCCATTGTCCTTCTGCCTCTGGGAGAGCCATATGAGGGCTTGGG
TAATGTGTGCTTCATCGATGAAGATGTAGGCTCGAGCTTGGGCAAAAGTCTTCAGAACAAAGGCTGTGAG
CCTGACCAGGGAGGAAGCAATCATGATGTTTATGTTGTCAAAATGGTTTTATAACCACTTCACAGCAACA
GGCTTCATATGATGTGAGTTAGCTAACAAAATTCTTGTGTACTTAGAGAGCTTATCTCCTTGATTAATCT
TTAGTCTGCCTGATTAATCTGCTAGATGTAGTATTTCCTTGCTAACTCTCTCTTTGCCACAGGGAGTCTT
AGTATATTTAATTTTATTTTAGTTCCGAGATACATGTGCAGAACGTGCAGGTTTGTTACATAAGTATACG
TGTGCCATGGTGGTTTCTTGCACCTATTGACCCATCCGCTTAGTTCCCTCCCGTCACCCCACACCTCCCA
ACAGGCCCTGGTGTGTGTTGTTCCTGTCCCTGTGTCCGTGTGTTCTCATTGCTTAACTCCCACTTATGAG
TGAGAAATGTGGTGTTTGGTTTTCTGTTCCTGTGTTAGTTTGCTGAGGCTGATGGCTTCCAGCTTCATCC
ATGTCCCTGCAAAGGACATGATTTCATTTCTTTTTATTGCTGCATAGTATTCCATGATGTATATGTACCA
CATTTTCTTTATCCAGTCTGTCATTGATGAGCATTTGGGTTAGTTCCATGACTTTGTTATTGTAAATAGT
GCCGCGATAAACATACATGTGCATGTGTCATTATAGTAGAATGATTTATATTCCTTTGGGTATATACCCA
GTAATGGGATTACTAGGTCAAATGGTATTTCTGGTTCTAGATCCTTGAAGAATCGCCATACTGTCTTCCA
CAATGGTTGAACAAATTTACATTCAAGTAATTTGAATGTACTTATTTTTGTTAGTTACTTGAGTAAGGCT
TTAAATCTCTCTTATCTTTAGAGATTTCCTTCTGCAGATGACAGAATCTTCTCACATGCAGCTCTTACAT
GCAGTAAATTTTAATATTGCTTTACTTTAGGGATTTAAAAAAATGTTTTATATTACTGTTTCCTTCTCAA
TTGTTTCCTCTTATTAATGAATTCATTCCAAGTCAAGCTGAATGACTTAGAATGTGACAATATAAGCTGA
AGTTAACATGGTTTATCTGGAAGTTATATATGTTCACTGGCAATATCATTTTAAAACTCATGGTTATGGT
AGCTACTTTAGAAAGAATAGCCATTTCAGAAAGAAAACCTTGGTACATTATTAATAGGATCCATTTTGGA
AACAAGCCTAACATAACATGTATTTGGATATCAGGTTTTCTTCTGATTACCTTGCTAATCTTGGTGGATT
TATCTAGTATAACAAACCATCGGTCTGATAATACATATCTGATAGTGTTGCTGTGAATATAATTGAGGTA
ATACATGTAAAAGAGCTGGCACACAAAAAGAAGCTCAAAAAATTGTTCTTTCCTTACCAGGTGTTGCCCT
GGTTCCTGCCATATCGCTCCCCAAAGGTGCTGTAGGAGCCATCATAGTGTTTGTAGTTCAACTGTCTCTG
GTAACCTGGAAAGGAAGATTAACGAAACAGCACAATGGATTAATGTGCATGCTGAGGGTGGAGAAATTAC
TAAAAGTACCTTGGCTTCTCTTGTGACATTTCTTAAATTTTGTTGTCATAGATTAGGAGTTTCTGAGCCT
TAAATATTTTATTGGAGGTTGGAGAGTGGATAGTTTCCTTGAAATTAACTATCATAGCAGCTATCATAGT
GAGCTAAGCTAATGTATCATAATATTCATAAGTAACTGAAACCTACTGGGAAATCCAGTTGAAATAACAT
TCAAGTTTTCCCTTACTCAAGTAATCACTCACCAGTGTTGAGATAGCCAATGGCCTTGGACTTGATCTCT
GGAGTAAGCTGCTGTGTTTCATTTAGATAATCCAGTACATAGATGTTAGGAGCAAAGAGGACCATATTCT
GCTCTCCACAGCCATAGGGCATCTGGAGAAGATTTTGTGTGTTTTGCATGGCAGAGCCTAATATGTCTCC
TAGAGAATGGGAGAGATGGGAAGTCATAAAGCTTGGAGATTATCATCTATCAAAGTCATTAAGCAGAAAT
AATTAGTTGAGCTTAGAAATTGAGAATTTTTAGGAAGGATGATTCTTCCAGGGATAGAAGTATGATTGAA
AGCAATAAACAAGCCCAAAGAAGAAGAGAAGAAAGAAGTTAAAATTATAGTATTATTTTTAGTAAATATT
TATGGGAAATAAAAATAGTATAATAGAAGCTGTTAATGCCCGGATCCACTAGGGGCTGGAGACTCACCCA
AAACTGAGACAGAAGCTCGGGCAGATTCTTCTACCACATTTGGTGGCAGTTTCAGGGATAATTCTTCAGA
AACCTCACCACCTAGAGAAATAAGCAAATCAGACATATGAAAATTATTTCTGCATTATATCTTTCTAAAC
AGCTCTATGACCCAGAAGCTAGGACTATGCCTTATACCTAAACTCCTCCTGAAAAGTTGTCCGCCTTTAA
TACAACAGTAATATATAAATATCTTAAAAATGGGCTACTGGTTTCCTGTGATTTTCAGAATTTCTTCTTC
AATGATCTTTTCAGTAATTTATGTAGAATCGCATGCCAAATAAGACAACAAATTGTAAGAGCCTGGTGAT
GTTGTGATTCAGTTGCTGTCATCTGATGGCTGACACAAGACGGTTATCACAAGATGATCTATTTAGTTCC
CACCACCAACTTCCTTACTCAACAGTTGTATGGAGAAAACACCAACAACAAAGCCCTATAAGTATACATA
AGTAAAATTACCCACAAAAGGTCCTGAATTCTATAATAATGCTATGTTCTTTCTTCAAATTTCATATACA
AAGATAGTATTTTTATGGAAAACCTAGAAAATTGAGGGTAAGGAAGTGAAGACGAACAGTATTTGATGCA
TTGAAAATAAAATAATTACTACTCATGAACATACATTTACTTCCATTTTAATCTTGGTAAATTATATGAA
ATGAAAATGAGAGAAGTATGGTATTTATTTTCATACTGAATCCCTTCCTCATAAAATTCATATTAAAATG
TTTCTTAAAAAAAAGCCATAAGCATAGTTAAAGGACAAATGGCTAAGCAAAATAAAATGCTTGACTCACT
GAAAATAAAATAACTGCTACTGATGAACATACATTTACTACAATTTTAGTATTGGTGAATTATATACAAA
TGAAAAATGTAGCAGTTATCTTCCCTTTCTCATAAAATTAATGTTAAAACTTTTGTAAAAAAACAGATGC
CATAAACAAAGTTAAAAAAATGACCAAGTGAAAGAAAATATCTGCAACATATTCAACAGATAAAGAATTA
GTGTCATACAACTGAGTCAGAAAAAAACTACTCAAAAGACAAATAGCCAAAGATTATAAAGGCAATTAAT
AAACATGCAAAAATAAGGTCATCCTTGTAATTAAGAAAATATAAATTAAAACAACAGCAAAATTTTTTTT
TCTAAATTTTTGGCAAAAATTAAAATTAAAAACTTTGATGGTAACAGATGATGGCAAATATAACACTATG
GAAATGTATCCTGGTGGAAGTATAAATGCATTTAGGTAATAAAGAGGAGGATTTTCGTTTTGTAGTTCAA
TTAAAATTCAGAATAAAGCAAGATGATGGACTAGAAAGTCTCAGGATCTTCCTCCCTCCACAGAAAGTCC
AACTAGCTGCTATCCACAGATCAGAAAATCTATTTTGAAAACCCCAATACTTGGAAACAAGTCTAGGACA
CCTACATTGTTCATAGAACTGAGTGAAGACAAATTAGAAGAGTAGGAAGAATGGTCTCACTTTGACCATG
TCATTGTTCCCACTCCTTTAGGTTAGCACAATGCCAGATAGAGAGGAGTTCCCTGGGGTCACAGTTTCTA
CAGCGGGGAAGAGAACCAGGGGTAGACATCAAGATTCTCAAGTATTCAAAGACACTTCTCAGGAAGCCCA
CTCTGGTCTCATTTCACCGGGAACACAGGAAGTAATGAGGTCAGGTAGAAACAAAGAAGGACAGAGCTCA
CAGTGACCAGCATGTGGATTTTGGTAGTGCTTCTGTGTTTCTGCCAGCTATGGCACCCATTCAGAGATAC
CAGCCAACTGCATAGCCCATCTGCAAAACTGAGCTGGTCACTTTCAGAAGCATGTTGGGAAGTTCAACCT
AGCTTGAGTTTCCAGATGGCCAGTCTGTAAGCCCAGCTTCAGAGGTTATGCCAGTGACCCCACCCAGGTA
GCAGACACCACCTCTGTGTATTTCATAGAAGTGTAGGGGTTAAATATGCTTGACCTGGGAGTCTAAAGGG
TAGCTCAACTCAGCCAAAACCTCACTCCATGGCTCCATTCACAAGGGTGGGGTAGCAATCCTCTATTATG
CACATCTAAGAAGTATAGTATTTATTTCTGCCCATCCCAAGCAACAACTCTACCTAACCTCACAGCCCGG
ATTGTGACCCTGCCTAACTTCAGGTCCCAAATAGCAGAATCATCCAGCCAGGCAACACATCTTGTGACTG
GCCTGACCAGAGGCCATTGTAGTACCCAGCCAGCAGCTCCACCAGATAGCAGAGACAAAACAGTGATCTT
GCCAGAGAGCAAGGCCCAACCAGTGGCCCTACCAAACATAAGAGCAAAGGCAGTGGCCCAGCCAACTAGG
GAACCCATGAAAACTCTGCCTGCTCAAGGTTGTCACCAACTGATCTTTCCAGAATTATAGGCTAGACTAA
ATAGCAAACCTTTATCCCTGCCAAAGAATACCTATAAAAACCAGAAGAAGTGGCTTTCTCCTCAAATGCA
CAAATAATGCAAGGACACAGGATTATGAAGAATCAAGGAATGATGACACCTCCAAAAGAAACTGGCCAAG
CTCAAAAAATTGACCTCATAGAAATAAAGATCTATGAAATCACTGACAAAGAATTCAGAATAATCCTCTT
GAAGAAATTCAGTGGACTACAAGAATATATAAATACAAAATTAAATGAAATTTGCAAAACAATACACCAA
CAAACTGAGAAGTTTGACATAGAAACGATTGTGAATAGTGCCACAATAAACATATGTGTGCATGTGTCTT
TATAGCAGCATGATTTATAATCCTTTGGGTATATACCCAGTAATGGGATGGCTGGGTCAAATGTATTTCT
AGTTCTAGATCCCTGAGGAATCGCCACATTGACTTCCACAGTGGTTGAACTAGTTTATAGTCCCACCAAC
AGTGTAAAAGTGTTCCTATTTCTCCACATCCTCTCCAGCACCTGTTGTTTCCTGGGACATGGATGAAGCT
GGAAACCATCATTCTCAGCAAACTATTGCAAGGACAGAAAAACAAACACCGCATGTTCTCACTCATAGGT
GGGAATTGAACAATGAGAACACTTGGACACAGGAAGGGGAACATCACACACCGGGGCCTGTTGTGGGGTG
AGGGGATGGGGGAGGGATAGCATTAGGAGATATAGCTAATGTAAATGACGAGTTAATGGGTGCAGCACAC
CAACATGGCACATGTATACATATGTAATAAACCTGCACATTGTGCACATGTACCCTAGAACTTAAAGTAT
AAAAAAAAAAGAAATAGAAACAATTATCTGCAACTTAGCTAATATTGTAAAATAAAAAATAAATAGAAAC
AATCAAAAAGAAACCAAATAGAAATCCTGGAAATAAAGAATACAATGACTAAAATTAAAAATTCAAAGTA
AGCTCAACAGCAGACTTGATCAAGCAGAAGAATCAGTGAGCTCAAAGATAGAGTATTTGGAATTATCCAG
GCAGAAGAGCAGAAAGACAAAAGAATGAAGAAAGCCTATGGAAATTATGGGACATCATCATGAAATCAAA
CCTTTGCATTAAAGAAAGTCCAGAAGAAGAAGAAAGAGACTATAAAGCACATTTAAAGCAATAATGAAAA
AAAAGAGTATAGAATCAGAAAAAAAAAAAAGCAGTAAGGGCTGAAAACTTCCCTAATTAGGGGATAGATG
CTAGCATCCAAGTACAGGAGGCACAGAGGTCTCCAGTGAAATTCAAATGAAAGAACTGCTCACTAAGACA
CAATAATTAAACTATCAAAAATCAAAGACAAAAAAAAATTCTGAAAAGCAGAAGGTGATAAAGAAACATA
TCACATACAAAGGAATTCCAATACAACTATCCATGGATTTTTAGCAGTAACCCGGCAGGCTGAGGGAGAG
TGGAATAATATATTCAAAGTACTGAAGGAAAACAAAAATAAAAACAACATGGAATCAAGAATTCTTCATC
CAGCAAAGCTGTCTTTCAGAAATGAGGGAGAAATAAAACATTCCCAGACAAACTAAAAGCTAAGGGAGTC
GTCAACATTAGGCCTGCCTTCAGGAATTACTGAAGGGAGTTCTTTAAGCTGAAACAAAAGGCCCCTAATT
AATAATACAAAAACACAAAAGCACAAAATTTAATGGTATAAGTAATATAGAGCCATATTCAAAATACTCT
ATGACTGTAATGATGGTATTTAAAGCAATTTTATCTCTAGTACAAGGGTTAAAAGACAAAATATTAATAA
CAAGCATAGCTAAAAATAAATTGTCAATAAATACACATTACAAAATATGTAAATTCTGACATCAACGACA
TAAAATGTGTGTGGGGGAGTGAAAGAATGCAAAGTTAAGTTGTTATCAGCTTGAAATTGACTGTAAACCC
CATAGTAACAGCAAGGCAAAAATCTTTAATAGAAGCACAGAACAAAAATTTTAAAAGATTCAAATCATAC
CACTACAGAACATCAGACCACAAAGGAAGACAGCAAAAGAGGAACAAAGAAGCAAAACAACCAGAAAACA
ACAAAATGGTAGTACCAAGTCATTTTTAAATTAATAATTACCTTGAATGCAAATGGACTAAATTCCCCAT
TTAAAAGACATAAAGTGACTGAATGGATTTAAAAAAACAGGACCGAAACATATGCTAATTACAAGAGACT
CACCTAATTTTTAAGGACACACATAGACTGAAAGTGAAGAGAAGGAAAAAGATGTTCTAGGTAAATGGGG
ACTAAAAGAGAGCAGGGGTAGCTATACTTATATTCAACAAAACAGACTTAAAGTCAAAAACTGTACAAAG
AGACAAAGGAGAACATTATATAATGATAAAAGGGTCAATTCATCAAAAGGATATAACAATTGTAAATCTA
TACATATCCAACATTGGAGCACCTAAATATATAAAACAAATATTAAAGGTTGAAGGGAGAGATATGTTGC
AATGCAGTAATATCAGGGAATTTCAACATCTCACTTTTAAAAATGGATAGATTATCCAGAAAGAAAATTA
ATAAGAAAACGTTGAACTTGACCAACACTTTAGATCAAATAGACCTAATGGATACATACAGAACATTTCA
TCTCAAGCACACAAGAAACATTCTCCAAGATAGATCATATTTTAGCCCACAAAACAAGTCTTAGCAAATT
TAAGAAGACTGAAATCGTTTCATCGTATCAAGTATCTTTTCTGACCACAATACTATGAAAACTAGAAATG
AGTAACAGGAGGAATTAGAAAAAATTCACAAATATATGAAAATTAAATGACATGCTCCTGAACAGCCAAT
GGGTCAATAAAGAAATTTAAAAGGAAATTCAAAAATATCTTAAGACAAATGAACATGGAAATGGAGCATA
ACAAAACATAGCATAAAGTAAAAGCAATTCTAAGAGGAAAGCTTATAACAATAAACACCAAAAAAGAAGA
AAAATTTCCAATAAAGATACTAATGATATTCCTCAGAGAAGTAGGAAAAGAAGAACAAAGTAAGCTCAAA
ATTGGCAGAAGAAAGGAAAATAATAAAGATTAGAGCAGAAATAAATCAAATAGAGACTAGAAAAAGAATA
CAAAAGATCAATGAAACTGAATTGTTTTTTTAAAAAGACAGACAAAAACTTTTAGCTAGGTTAGCTAAGA
AAAAAGAGGGAGGCCTTAAATATATAAAATCAGAAATGAAAGAGAAATTATGGCTGATACCACAGAAATA
CAAAGGATCATAAGAGACTATTATGCATAAGTATACACCAATAAATTGGATGATCTAGAAGAAATGAATG
CATTCCTAGACATATACATACTACCAAGACTGAATCATGAAGAAATAGAAAATCTGAACTGACAAATAAT
GAGTAAAGAGATTGAATCAGTAATAAAAAGTTTTCCATTAAAGAAAAGCCTAATAACTGTTGGCTTCACT
GCTAGGTTCTACTTATCATTTAAAAAGAATGAATACCAATCCTTCTCAAACTCTGCCAAAAGCTGGAAGA
GGAAGGAATACTTTCAAGCTCATTTTATGAGGCAAGCATTACCCTGATACCAATGTCATAAAAAGACATT
ACAAAAAAGAATTACAGACCAATATTCTTGATGAATATAGATGCAAAAATCCTCAATAAAATACTAGCAT
AGCAGCTAAGCATGGTGGCATACACCTGTGGGTGGCTGAGGTGGTAGGATTGCTTGAACTCAGGAGTTCA
AGTCCAGCCTGGGGAACACAGCAAAAGCTCATCACTTAAAAAACTAAACCAACCAACCAACCACACGAAA
TAAACTAGCAGACTAAATCCAACAATACAGTAAAAGGATCATCTACCTAGTCAAGTGGGATTTATCCCTG
AGATGCAAAAATTGTTCAACATATGCATATCAATAAATGTGATACATTACATTTACAGAATGAAGGGTAA
AAACCATACCATCATCTTGTTAGATGGAGAAAAAGTATTTGACAGAATTCAATGCTCTTTTATGATAAAA
CTCTCACCAAATTAGATATACAAGCAATGTTCCTCAACACAATAAAGGGCATGTATGATAAACCTATAGC
TTACATATTTAACAGTGGAAAATTGAAAGACTTTCCTTTAAGATCTGGAACAAGACAAGGATACCCACTG
CCACCATTTATTTTCAAAGTAGCACTGGAAGTAGCAGCAAGAGCAATCAAACATGAAAAAGAAATGAAAA
ATATCCAAATTGACAAGGAAGAAGTAAAATTTTCACTGTTGGTGATGACATTATCTTATATATTGGAAGC
TCAAAAGACTTCACCAAAGGGCTGCAAGAACTTATAAATGAATGCAATAAAGTTGCAAGATACAAAATTA
ACACATAAAAATCAGTAGTATTTTCTGTTCACTAACAATGAATGATTGAGAAAGAAATAAAAACAATCCC
ATTTACAATAGCTATAAACAATATGTAGAAATAAATCTAATCAAGGAGGTGAAATGTACAGTGAAAATTA
TAAAACACTGATGAAAGAAATCAAAGAGAACACAAATAAATGAAAAAAAATACAATGTTCATGGATTGGA
AGAATTAATACTGTTAAAATGTCCACACTACCCAAAGCAATCTACATATTGAATGTAATCCCTAACAAAT
TACTGATGTCTAGTTATGGAATCATAAGTGTCATCAACAGATGAACAGATAAAGAAAATTTGGTATATAC
ACATAGAATTCCATTCCATTTTAAAAAACAAGAACATTCTGCTATTTATGGCAGCATGATTAAATCTGGA
GGAGATTATGTTATGTGAAATAAGCCAGGTATAGGAAAACAAATATTGCATGTTCTCATTTGTATGTGGA
AGCTAAAACATTCAAATTCACAGGAGCAGAGAGTAGAATGGTGGTTATGGAGGATGAAGCTGGAGTAAAA
GGAAGGTGGTGTTCAAGGGACACAAAGTCTCAGACAGAAGGAATACATTTTTTTCTTTTTGGGATCTATT
GCACAGCATGGTGAATATAGTTAATAATAGTGTATTTTATGTTTCAAACTTGCTTAGAGAATTTCAAATG
TTCCCACCACAAAACATAAGTATTTCAGGTTAGCTTGATTTAATTATTTCACATTTTATTCATAAATCAT
AACATCACTTTGTATGCTGTATATATATACAATTATAAATGGTCAGTTTACAATGTAATTAAAGAACAAC
AACAACAACCAACCAAACAAAACTATGCATATCTATGCATATGCTCTCTGACTCAGGAATTTAACATTTT
GGATCTACCCTAGCTGTACTTGCATATGTTCATTAAGAGGCTCTTATTATAATTAACTAACTAATTTTTT
AAAGCTAGTGAATAGTTGAAAAAACCAATATAGGAAGACTAAAACACTAAGCAGAATTGTGATGTATTTA
TATTATAGGCTTAAAAGCAATTCCAAGGAAAGACCTAGATCTACAATTTAACATAGGTAAATCTCCAAGA
CAGGATGCTGAGTGAAAAACAAACAGTGATTTATAGAATGAAACTTATACAGTTTATTATATGTAAATCA
CACATCCACAAACATATACATCTACACACATTATTTCTAAAGATAAATGGATGGCAAAGTACTGAAAAAT
GTTCAGGGGGGTGACATTAACCTTTAATGTGATGTTCTGTTTTTTTTTTTAAAGAAGAATATATTTTTGT
AAAATTAGGTAGGCACATTTGATTATGTTGGTAATTAAAATGAAATTTAGTAAAACTATTTGATGATTAG
CCCTTACACTTAAGAGATACATCAAAATGAGTAACTCAGAAACGGAGAAGTCATGATAAAAGGATTGAAT
GATAGGTAATCAGTTCACTTAAATGTAGAAATAAGGCTAAATGACAAGGAAGTTATGTTTTTAGGGTACA
TTTTATGTGTTACATCTTGGCAACAGATGAATAGATAAAGTATTTAGTACGAAAAACATACTAAATTTGT
AGGTAGTCAGAGAAAGGCAATGAACCTATGTATGATGTTGATTCAATGTTGGTTTGGGGTGAGAATGCAT
TGTGCTGATAAATTTCTTAGTGTATTAAATTTTTCCTGTAAGTTTCTTCAGTTCCTTCTCAAATGTTTGA
TAGGGCATTAGGTACGGGATAGGCATCAAACAGATATTAATATGACAATAATGGTAAAGGCCATGACAAC
TTTTCCTTTGGGAAATAGCAATCCCGTTATCAAATACTGTTGGCTATGTAAAACTCAGTGTTAGAATGCC
CTAAATTCAGCCGTCCATAGTTTGCATTATTAATTATTTAAGGAAACATCCCTTTTGGTAATATTAATTT
TGATTCTACCCACTTTCTACCTATGCCCATACCATACACTGGTCAGAAAGTCATTTGGTGTTTGCACAGG
TGCTGCAAAAGATCAAGACTCAGAATGCAGGCCTAGGGATATTCTGATCAAATTACTTGGCCTTCCTAAG
AACTATTTTCCACATTTGTCAAATGCATTGATGGTGCTTCAGGTCTTAGATCACAGAGAAAGTGTAGGAA
TAATATATAAATGTTCTTTGAACTTTAAATGTTAGACTTTAATGTTTTTTAAATTATGATGGTTGACTCT
TACCTGATGGACAAAGTAGGGAGTTGAATGTTGTTTCCTTCTCTAGTCCTTCAGGCTTTAGGTAAAAGAA
AGAAAAGCTAGTGAGAATGGACTGACCTTCAGAACATGTGTTTTAATGGAGGGACCACAGATATTTGGAT
AGTGAAGAGAAGGATTTGAACTGTATTATCTAAGAAAATTCTGTACATATAAGCAATATACGTAGGAGGT
AGTTCGATGCATGAACAAATGAAGGAAAAATTAAGAAAGTAAATCAAAGGGAGGCTGTGCATGGTGGCTC
ACACCTATAATCCCAGCACTTTGGGAAGCTGAGGTGGGCAGATCACTTGAGGCCAGGAGTTCGAGACCAG
CCTGGCCAACGTGGTGAAATCCTGTCTCTACTAAAAATACAAAAACTAGCTGGGCGTGGTGGTGCACACC
TGTAATCCCAGCTACTCAGGAGGCTGAGGCACGAGAATTGCTTGAACCCAGGAGGCGGAGGTTGCAGTGA
GCAGAGATCCTGCCACTGCACTCCAGCCTGGATGACAGAGCAAGACTCTGCCTCAAAAACAAAAACAAAA
ACCCCCAACAAAACAGAAAGTAAATCAAGAGAGAGATAGGACAGAGAGATACATGAGAATAATATTATAA
AATATCCATATATTATTATATTACCCACATATATTATATATTATTGTGGACTATATATTATTTAGGTTTA
CTTACTTCAACCAACAGAGGCTTGATGACTGTGTCTTTCCTTCCGTGTTCAGGAACTGAAGGCACCTCAG
TCCCACACAGCTCTTGAGACTCTAGTGCCTCTGCGCTCACAGTGAAATTCACATTTCCTGAAAAAAAAGG
CCAGTAGAAATGAATAGCATCTTCCCCTTCCTCCATGCCTCCAAACTCAAGATTTAGAAATGTTCAATGC
TCTGTAAACTTTTGTTTTATTAAAACACAGAAGCAGGAACGGAAACATGCAAATGAGAGGTGAATGATAC
TGAGAATTCAAGGTGGAGATGTTGAGGATATCCTTGTAGGCATCTTAGAATAAAAGGCAAAGGAAAAAAA
TCGCAGCATCTAGTGGTCTTTTCCTGAAGGAAGTAGCACTCAATATAAGGTTCCCACTGCCATATACAAT
CTTTGAGTAGAGAATTATCTCTAGCAGTTTTTTGCTCACCTAATGACTTTGGGGTTACTGCCCAGGACAC
AGTTTGCCGCCCGTTTGCACAGATGCAGTGAGGCGCTTGTTCCTTCTCCACTGGGACAGCTAGGAAGGCG
GGAGAGGCTTCCAGCTGCACACTGACCTGAAACCACACATAAGAAAGGGAGTAGAGAGGGAAGGAGAACA
GAGGGAGAATGGGTTTGAAGTAAAGCATCTTGAGGAATTGGTTAGATTTCAGGTTGCCTCACATTAAAGA
TGATATAAATGAAGATCAAGTACCTGAAATATATTTAAGTGGATCTTAATGTATCAGATTTACACAGGTA
AATCTGAGTTATTTTGGAAGCAACCTGCTCTTTCACATGATGGGACCAGAGGAAGGGAAAGGTAATGATG
GCATGCTGCTCTACCTCTTTGGTCTGGAACTTTGACCATTCCCCCGGATCTCCCGGCAGAGGATACAAGA
CTTATAAACAGTTATGGTTTCAGCAAAGGTAAGATGCTCACAAACGACTTTTAAAATTAGGTTTAATATA
ATGAATGAGCTACGAAAAGTTAAATATATGAGATCGTAGAGGTTGAAACCTTGTAGAATCTGTCATGAGA
ATAGAGTACTGACTTTTGTCACCCCTGTCAGAATTCTTCATACCACACAAATACTAACTTTGAAGGGTTA
TAAGGGCTAGAAACTTGCTTTATGGTGCAATTTGGTATTTGGAGATCTCAAAACCTGTAACTTTTACAAT
CATGAATATCTAGTAAGCATATTTTGCATACAAGAGTTTGCAGTATTCCTAGGAATGCAACTTTTAATTT
ACTTGATGGCTACCTTGTATTTAATTTAGGAAAGAGATCCTTACCCGGATGCATTTGGGAAGGTAGTTTA
GGACCGTGGCCTTGAGTGTGAAGGCCTCTCCACGAATCACAGAGTAAGGCATTGTGAGCTCCACAAAGAA
GGGCTGGAAGGCTCGGAGAGAGGCAGTGGAAGAGATACCAAGTCCAGCATCTTCAGACAGGCAGAAGGCC
CCTGCCTTCCACTCGGTGATGGTGTCAGGGACTGTTACTCCTACCTCAGCCACACCTGCTGAGCTGGAGA
GGAGTGTAAGTGAAGAACAGAAAGTAAGCAGTTAAATACATCCTTTCTAGGGAGAGAATCCCTAGGAATG
ATTCTACTGCCATGACTTAAAAACACTCAATAGAAATACCAATAATGGAGAGTATAATCAAGGATTGAGA
TGGGAATATAAGTCCTTTTCTTCCAACTGTTTTTAATTGTAGTATATCAGAATTGTAGCATAATCTTTTA
CAGACAATATAGTTATAAATTTAACATGCAGTTTGAGATTGTTCTTAAGTTCTCTTCTCTAAAATGCTAT
TTCACTGAGGGCTGCTTTATAATTTTAAATTCTACTACTATTGTGTATAGTGGGCCTGACTGAATCTGTA
TTTAACTCAGGATTGCTAACCAGTGAGGGATCTCTTACAGGCAATCTGTGCAGTCCTTGGTTGTATTAGG
TCCTTATGCCCATTTTCTGGAAATCTTAGAATTAAATTTGCACAAAATTTTTTAGCTCTGATGCAATTAG
ATTAGTAAGACTTCTTAGCTGATGTATTTATGTTAAACATCTCCTGAAATTAGCAATGCGTTTGAAAGAA
GTACTTCAGTACTGAAAAATTAGCTAACAGCTCCCAGTTTCTCCCTGGAAGGGCTTCGTCTACCCACTTT
ATCAGTTGCTGACTGAGTGTTGGGCTTCTAACTAGCCTGCACTGGGAAGCAGAAGGAGCAGGGAAACGAC
AGACTTACAGGAAGGCTGAAAAGCAGTAAGGGCACTTCCCATGCCTCCTTCCCCTGGCTCGCCCCACGGA
TAAAACCAGGTCTGAACATACCCCTGGGAATAATTTGTCTATGCATCAAGCACCCCAATGTTTACAGCTC
GTACCTAAGGGTCTGGCTCCTAAATCACCTAGCTCCAGGAGTAGATGGAGCTCTGCAATCAGGAGTCTCC
CTAGACCACAGTGAACACAGAGGTGGTTTTAAATAGGCCTTTGAGCAATGCCAGTGGCTACCCGCCCCCA
CCACCCCTTGGCTCAATACAGAGAGAACAGGCAAAATCTCCCATTTCTGGCTGTCTCCTAAGGGTTGGGC
TTCTAAACAGCCTGCATCTGGGAGTGAAAGGGAGAAGTAAACAAGACTCCAGGAGCCTGAAAGGGAGTAT
ATGGCCATTCCGGCTCTTTCTCTCCACCTGCCCCACTGGCTTGTTTCACGGATAAAACTCTGTTTCCAGT
GTCTCTCTGGAAGGAATTTGTTCACTCCCCTTGGTGCAAATGTACATTGCCACAGCCATTATGGAAAACA
GTATGGAGATACCTCAAAAATTTTAAAATGGAAACTACCATATGTCCCAGAAATCCCTCTTCTGGGTATA
CTCCCAAAGGAAATGAAATAAGCACCTTGTAGAGATATATGTGTTTTGGTGTTCATTACAGCATTATTCA
CAGTTGCCAAGATATAAAAACAACCTAAGTGTCTGGGTGAATGGATAAATAAATTGTGGCTATGCGTAAT
GGAATATTATTCAGCCTTAAGTGGAAGAAGATCCTGCCACTTGTGACAACATGGATGAACCTGGGGGAGA
TTATGCTAAGTGAAATAAGCCAGACACAGGACAAGTACTGCGTGATCTTACTTGTATGTGGATGCTAAAA
GAAGTTGAATACATAGGAACAGAGAGTAGAAAGGTGGTTGGGGTTGCAGGGATGGGAAGAAGCAGGTCAA
AGGGTACAAAGTTGAAGTTACGTAGGATGAATAAATTTAGAAATCTAAAGTACAGCATGAGGACTGCAGT
TGATAATACTGTATTGGATACTGAAACTTGGCTAAGAGGATAGATTTTAGGTGTGCTTGCTATGCACACA
AAAATAGGTAACAATGTGAGCTAATGGATGTGTTAATTTGCTTGACTGTAGTAATCATTTCACTATGTGT
ATGTGTATATATATATATCAAAACATCATGTTGTACATCATAAACATATAAAACAATAAAAACAGAAAAA
CTAGCAAAGAGTTGAAAATAGTCAGGGACCTCTATTGTTGCATATTGCATATGCAGGAAGTTACTTACTT
TACCACCACCAAATCCCAGATCCATGTCTCAGGGAAGTACTTTCGTACGGTCTCCGTGTGAGGCTCTTCA
ACATGCACCAGGCGTGCATGGCCTCTTCCCATTACATCTGACTCTATGGTGAGTGAGGAAGAAGACATTA
CAATAAACATACAGATAAAGCTTATGAGAGAATGTAATAGTTGCCACCAAAAAAAAAAAACAAAAAACAA
ATCGTCTGATGAAATAGAGAGGAAGGAGGAGAGGGCGCTTGGGTCATCAAGGAAAGCTTCTTTGAGGAGG
AAATATGTTGGTTGACTTAACAAGCCAGGAGAGGCCGGGCGCGGTGGCTCATGCCTGTAATCCCAGCACT
TTGAGAGGCCGAGGCCGAGACGGCGCCACTGCACTCCAGCCTGGGCGACCTGAGCGACAGAGTGAGACTT
CGTCTCAAACAAACAAACAAACAAACAAACAACAAAAAAAAACAAGAATAAGCTAGGAGTGAGCTGGGGG
AGGAGGGTCATAAGCAGAGGCTATAGAGACTTTGGCAGACAGAGGCTTGGATTGTCTGTGGGGCACAAGG
ACTCTGTGGAGTCCTATGTGGCTGCTGCCGCTGTGCTAAGTGGAGAGTGTTATGACACAAGGCCGTGAAG
AGGGGCAGGAATCCAAGTTTCCATTGGTGTGCTCCTCTGCAGGAGCAAGGAAAAACTGACACACATGTTA
TGACAGTGGCTTTGAGAAACAGTTTACAGGAGGGAAAAGTTTAATAATAATAAAGACTTTTTATTCTCTA
TCGTGTCAGAAGATTACAGTTAGTTTCCTTCACTCTATTCACCTTCTATTAAGGGTGTGCTGGTCAATAT
TTCACAACCAGCTCTCTGGAAAAAAAAATTGTGCATATATATATATATATATATATATATATATATATAC
CTATACATGCATAAATTTACTATATATCTTACTGATAAAGGATTATACAATATAATTTATAAATAATAAA
ATATGCGGTAGGCTTCATAGTGAATTCCATAGAGCCAACTGATTCTCCTTAAATGCTTTCCTTGATTTTT
GACCCTCTTTTCTCTGTACTCAACTTATCCTCAATCATGATTTGACAATATGGGACTATAAATAAATGCT
TGATTACTATTCAGTTCATCAAAGAAGTAGCTCATGTCATTGATGAATGTGTGTGGTTCCAACATAAATA
TTGGCTGATGTTTTGGGGAAGTTGAACAGCTTTTTTACCTGACTGATGGAGAATGTAGTGTTGTTGTGTG
AACATTTCTATTTCTGTTTACACTAATCCTACGCTTGGAAACTTTCTCTTTCCTTTCAGCCTAACACATG
TACCTCCATTTACTAGAATTTGAGTTTATATTACTATATGACCTTGAGCAATAACCTTAATATGTATGAC
TCACATGTCCTTTTTGTTTGTTAATTTTTGTCACATTGTATCTTTTAAAAAATTTAAAATTTGGTGAATA
TATTAGGCAATATATATTTATTAATTTTTTGTTTACCATAAAAACCTACACGTAGACCTTCAGGTCCATG
CATTTCATACTGTTGAAGCTGTGGACACATTTTGGGTTTACGAATCTTTGAGTTGGTGAATGCCTTTAAG
CCCATGTCCTGCAAAGAAAATTATCATCTAATCAGTAAATATATATTATAAAATATACATAGGTAGCTAC
TTCTTTTTATTGAATTTGACAAGCAATCCAGTTAACTTAAATTAAACTTTTAACATTCACATCTGTAGAA
GGGATATTTATATACTTAAGGATGTAATTTTATTCTTTTCATTAAACTCTTTCAACAGTAATTATTTTGT
ATATGTGATTTTAATAAACATCACAGAGCAATTAATTCCTGTGAAAAAAGAAAACTTGAATAATACTCCA
AAAAGTTCCAGCTTAGTTCAGCAGCTTTTCGCAGATCTGCTGCTATTAGTAGAGAAGCCACTTACCTCTT
TATATCCCATTACCCTCAACTAGGACATGAAGGCATTCAAATACAGACTCTTTTCCATGTGTAATATTTT
AAGAAGCTTAAGATCAGACCATCTGCAACATAAGGAGTTTACCTCTAGGAAGCTGTACATATCCTTTTCA
TTTGTACTTGATACTGGAGTATATGTGATTCCATTAATATAGACATTATGACGATTGATGCAGTCTTCAT
TGTCCTGGTCATTCAAAGGCCCAGGGAAGCCAGTGAGGTCCTTTTCTGGTAGCAGGTTGTAAACCTGTAC
AAATACGAAAGACAAAAAGGCAAACTTATTTGTGACTTTTTTTTTTTTTTTTTTTTTTTTTTTTGAGACG
GAGTCTCGCTCTGTCGCCCAGGCCGGACCGCGGACTGCAGTGGCGCAATCTCGGCTCACTGCAAGCTCCG
CTTCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCCGCCACCGC
GCCCGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCTTGTTAGCCAGGATGGTCTCGATCTC
CTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGG
CCTTTGTGACATTTTTTAAGTTCAAGGAGAAAAGAACAGGAATAATGAACATCCGTCTTTCTTTGAGCGC
TCTCATTGCTTTGATGATTTATAGAGGGTATGGATCATTTTCTTGACACAGTGTTTTCATTTTGAAGATG
TTTAACAATTTTAGGAAAAACCAAACACTCCATCTAAGTACTCATCTAAGTACTAAGTACTACTTCGTTA
CACAGTTCAGAGGCCACCACTAGACTCAACACTGGAATGAAATAAAACTTTATTAATTGAAAAATCGAGG
TCTGCTGTATTTGTGACATTGCACAAAGCTTTGAGATGATAGAAGGAAATGATAGTTTTGTGCTTATCTT
GTGGTGAGCAACTGACTCAGTATATAGCAAAGTTAATGGGTGCATGTTCTAAACAGGCACACGAATAGGA
ATATCCTCTCTCCACAGGACACGATGGCATTTTCTTAGGTATTATTAGTGGAAACAAAATGCTCCAGATC
TTCATATAATACATACAACTTTAACCGTAAAATTCTAGGCATGATGCTTTCAAGTCCATTTGAAGGTGAG
AAGTAAGACAGACATAAAAATTGTGATAGTTACATTGCATTATATTCGTAGGAGTTTAAAACTGATTGAC
AAGAACAGATGAGCAAAGTGAGTGGTGTGATGAAATTAGACACTTTCTCAAAGTATCTTAACATTTCTCA
TTTCCTCTCCCTGCTTTTATTGTGGCATATTGCATAATTATTGTCTGTCTCATCTATGGGACAGACAATG
TAAGTTCCATGAGACATACATTTTTATCTTTCCAGTAGCTCACTGCTTGATCTCTACTAGCACTTAGTAT
AATACCTAGAACACAGTGGGCATTAAATAAATGTGTTGAATGAATGACCTACACTAGTAGCAGCAAAGTG
TTTCATTGGTAAGACACTAATCAAAGCTTGAGAAGAGTTGGTGTTTTAACTCAGGTCTACTACTAAATCC
CTGAAAGCTTCTGCTTTATTATTAATAAATAGGACTGTCTGCCTTATCTACCCATCAGGGTTGTTATAAT
TTGAAAAATTCTTTGAGAATTATAAAATTATATTATAAAAGTATAAAACATGTATATTATTTTCCCACAT
ATCCTCTTGAGATCCTACTGTTGAAATGTACTTGATGCTTCCTTTAGAAGTATTCTAATATTTTCAGTTA
AAATCCCATTAGAAGGACAAACAAGTAAGAAACATTTTTTTATAAGTTTCTATTTCAGGAAAATAAAAAT
ATAAATTTCTCTTTGTTAAATTATGGTAGTAGAAAAAGCTTCAGTAAGAGGTTATTACAATTGGTCTCAT
ATTAAAAATTTGAAGATGTGAGCAAACTACTATTAGTACATGCTATTAACTAGTTTTTGTTGTTCCAATT
CAGCATATCCTTTTGGTATTTCTTCTATTAGCTCCATATTTTCAAAGAGTTCAGTTATCAATGTCAATTA
TATAGTAGTTCAATTTCCCTAAGTTTTGTTCCTCAGAGATAATACATATGTTCCCTCAGAAATTATGTGT
AGCTTGGGACAGCAATTATTTCAACTGATGTAATTCTTTTTTTTTTTTTTTTTTTGACACCAAGTCTTGC
TCTATTGCCCAGGCTGGAGTGCAGTGGCACGATCTCGGCTCACTCAACCTCTGCCTCCTGGGTTCAAGTG
ATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGATGACAGGCGCCCGCCACCACGTCTGACTAATTTTTGT
ATTTTTAGTAGATACGGGGTTTCATTATATTGGCCAGACTGGTCTCAAACTCCTGATCTCAAGTTATCTG
CCTGCCTTGGCCTCCCAGTGTTGGGATTACAGGCGTGAGCCACCAGGCCCAGCCATAATTCTTATAAAAA
CGGAAATCTGATATTTCATTTAGCCTGTATAGCCTCAGTGCAGGTATATGTATCACTTTTGTTAGGCTTT
TTGAAATGTTGAAACTAGTTTGACAACTCCTATTACTGGTTGCATGGAGCTCTGGGATTTTAAGGACTTT
GGGTACTGTATGGTCTTTTTACATTTTAAATATATAATTTTCGAACGGCTTCCCCGGTTGCTCAGTTAAT
CCTTTCTTTTATTTTGCATAACTGCACTTCTCATATAGCACTTTTCACAATCTGCTCTGTATTCTCTCCA
GCCTTGCATATACGGATGTCCTGACACAATCAGAAGATTTGAATTTGTATTGCTATGTGCTCTTGAGCAA
GAAGCTTAACGTGTCTGAATAACGAGTCCTTTTTTGGTTGTTAATTTTCATCACATTTTGTCCTTTTAAA
AATTCTTTTATTTGATTCAATATATTGTATTTTGTTTATTTTTTTAACTGCAGAAGTGAGTAGTTATATA
TATATATATATATAATTCCTTACCAATGAAAGCCCACAAGAGAGCTCAAAGCAATTAATTCCTAGATAAA
TATAATTTTAATTGATCTTATCCTACTTATCCAGTCATTTTTCCTTGCTCTGAGCCCCTGGCACGGCCCT
TCTTGATTCCTGAGGCTGCCAGGAACTCACCGAGGACGCCGAGAGCTCAGCATCAGGCTTCATGAGCAGC
ACGCTTTGGTCCACAGCACGGAGGGCGCAGACGGACTGAGGAGCCGCTGTGACTCGCAGGTGGGCGTGTG
AGGCTGGGAGACTTTGTGATGGGCTGAAGCTCAAATCCACCTGTGAAATTGGAACAAAAGGTCAGAAAAG
CAAATTTCCAGGTTTACCCATGCATTCACTCGCATTTGCAGAGTGTTCCTCATGTACAATGTATAACCAC
TCTGCTTGACTTCGTGGAGGGTTGGCATTGTGTCAATCCTGAAGCTTTTTGTTCCCTACACTTCTCTTTC
ATTCTCAAGAATCACTTGAGCCAGTAGAATTATTTCTAATTATTCTTATAAATTACTAGTCATGAAATGC
CATTTTTATCTTTGATACACGGCAAGGTGCTCATTAATTGTGGTGGGACATGCATGGGTCTAGGTGCTCT
TGCATTTTTCTTTTGGCTCCTTAGTAGTCTTAAAAACTTGCTTACATATTTCCCAACGTTTCATCATAGA
AGAAGGGAATAACATACTCTGAACTGTGTAATTGGTAAGAGGCACTGCTAGGAGAAGTTTGAGAGTTTTG
TATAAGGAATCAAGTGATTCTGCTTCTTAGTGTGACTCTGCCACTACCTTGCTGAATGTCTCTGGGGAAT
TTGTTTAACCCTTTTGGCCCTAATGTTCACATGTGTAAAACAAATGATAACAATAGTAACTTCTAGTTTT
ACATGTTGAAGATTTTATGATCTAAAACACACACCTTGTTGGCCAGACAATTTTCAACATCATATTTTGC
AGAATCCCCAATCACGTCCCCGGTAGGTAAAACAGCATAGATGAGCAACCGAGCGACAGGAGCAATGTCT
GACTTCACAGGGATTGAGATGGAAAAATGGCCCTTCACTGGGGCACAAAGAGAATGAGAGGAAGCCATCA
TAGGTTAATGACTATTTCCATTAGTAGATGTAACAGACATAATAAACAGTAGATGTAACAAATGGATGAT
TACCTCTAAGGACTCTAGCTTTAGAAAAAAACCCTATCAAAGCCCTCTCTCCTCTCATAAATCATATACT
CTGTTGATTTTTCACCAGCTTTAAGCTTCAGCTCACCCACCTAATGTTCTGATGCTAGTTAAGGGTATGA
AGACATCCAATTCACTACCATTTGATCTAGGCCTCATACTAGAAGAGGGAAATAGAACCTGAAGTTATGA
GATGTAAGAGTAAGAGTTCAACACATTGTATTCATGCTACATGCTCTTTAACCTTCTATGAGCCAATATT
TGGTTCTTTCTCCATAAGAGGAACACCATGCTCCTTCAGAAGTTATTTTTTGATGCCTATGTAGATTCTT
TAGAGGTTGCATTAAGTTTCCTTCAGTCTGCTATGGTGCTTCTGTGTTGCTACAAGAACTAATGAGAGAG
TAGATTACTGATACTTTTCTAGCAAGTTATCTTTTAGAGTCTACTAGACTAGGAGCAACCTTCAAAGGTT
TATATTATGACATATTTGCTCATGGCAAGAGTCCGCTTCAGTCGGTAGAAGTACCCAATTTAATGCTTCA
TAAATCATAACTATCTTGAAAGGGAAAAAAGATATTTATAATAATATAAATGACATAAATGACTCAGCAC
AAGACCTGGTATATACAACATACCTTGAAATCGTACATTTTCTCCACCCCATTCTCTAACACAATTCTCA
TTTTGAGAAGAGGTTCAAGAATATTTATGGTTTAAAAATCTGGAATAAGCATAGATTATACACAACAATA
TTTTATGTATTTTATTTTTCCCCCTTTGTTCTTATTTATTTATTTATTTATTTATTTACTTTTATAGAGA
TGGGGTCTCACTATGTTGACCAGGCTGGTCTCAAACTCCTGACCTCAAGAGATCCTCCCATCCCGTTCTC
CCAAAGTACTGGGATTACAGGCGTAAGCCATCATAGCTGGCCCACACCAATATTTTAAATAACGCAAAGA
AAATAGGCTGAAAAAAAAGACAACACATATTTGATAAAGGGTGAGAAAAAAACCATTATTGTTTTCCCTC
CCTCAACTTTCTTTTAATTAATATTAGATGGAAATGGTCTCTCGTTACTTGAAAGTATTCCTGATATTCC
CAGCTCAGGAATGGAAAACCAAACATCATATCTTCTCACTCAGAAGTAGGAGCTAAGCTATTAGGAAGTG
GCAGCTAAGCTATTAGGAAGTGGGAGCTAAGTTATGAGGATGCAAAGGCATAAGAATGATACAATGGACT
TTGTGGATTCAGGGGGAAGGGTGGAAGGGGGTGAGGGATAAAAGACTGCAAATTGGGTACAATGTATACT
GCTCGGGTGATGGGTGCACCAAAATCTCGGAAATCACTACCAAAGAATTTATTCATTCATGTGACCAAAC
ACCACCTGTTCCCCCAAAAACCTATGGAAAAAAAGGGAAAGTATTCTGATACTTCCGTGGTGTAAGGCTG
AATGGGTCAGAATGGGGCAGCAATGCAGAGATGATGGAAATACTCACTGTCTTCCTGCTTCACAAGCAGT
CCATGAGTCCCAGTTCGGACAATGCCTCCCTTTGCCATTATCTGCAAAAAAGGAAATAAAAAGAAATTAA
ATGTGCCAGAGAGAACACGCTTCAGTCTCACTTCAATATACTTGTTTTATTGAGTCCCTGCCGGCAATAA
TTCACCTCAAGAGAAATCAAACTTTCAAAAGGAACATGGATAAGAAGTTGAAGTAATGACATCTAAAGAG
CTTCATGATTACTTGCTCCACAGAGAGCTTTTGTCTACAGTGAAGTCAACGCAGTAACCTCCCTTCTCAC
CAGATAATAGAAGGAGAGCTTCTTCAGCCCCAGCAGGGTGCCTCCATTCAGAATATAATGTGCCTGGACT
GTCTGAGTATGGCCACAGGGTAGTTCATGAGACATGGGCTCAAGGTGGACAAAGCTCTTGCTTGGGGAGA
ACACAAGATAAGCAGTGTGATGTGCCTCTTCGTGTTCTTCTGACACCCACTGGTAGCCGTAACAGGGACT
ACGATCCTTGTAATTGACCTAATGAATTAGAAAAATTATATTATTTTTAGATTATACGTCATAAAGATTA
ATGTTCTCACAAAACTACGTAAGTTTACTGTCCTACCTTAACTAGTAGCTAGAAATCTTTTGTTCCACAA
TGAAAAGTGGGAGAAGGACCCCTGATTTTGTTTCTCTGCTTCAAATGTAGGCATGCTTTGTGACTTTACA
CTGCAGAGCCTCCTGGGATTGAGATTTATATTTCTTAAGAGCATAAAAGGAGGCATCCTTTGCTCTGATT
AGCTTGCTTGAAATTTCTTTGACTGCTTTACCTGTGCAATTAGAGACACTGGAGCTATGAAACTTCATTG
AGGAGAGTAAATAATCTCTAGAAATGGAAGAACTGTGCTTTCAGAAAGCAGCTGCCTCTTTTAGGGTGGA
TTTTGAATGGGTATTATGAATAAATAAAATATTGTAACCTTAGGGGTCTGAGAAGACATTGGTAGAAAGC
ATTGGTTTAAGAGCTGAGCTGATGAATTAGCTGAAGTCTACCTCTTCTGGGCTATCTTAGGCTGATTGCT
ATTATTATTATTTTTTTGAGACAGGGTTTTGCTCTGGCGCCCATGCTGGAGTACAGTGGCACAATCTTGG
CTCAGTGCAATCTCTGCCTCTGGGGCTCAAGTGATCCTCCCAGTCAGCCTCCTGAGTTGCTAGGACTACA
GGTGCATGCCACCCCACCCAGCTAATTTTTTGTATATTTTGTAGAGACAGGGTTTCACCACGTTGCCTAG
GCTCGTCTCGATCTCCTGGCCTCACGCAATCCACCCACCTCAGCCTCCCAAAGTGCTGGGATTACAGGCG
TGAGCTACCGTGCCTGGCCTAGGCTGACTATTTTTAATGCTCCCTGCAATCTGGATTCTAATACCTCAGA
GGCCCTATTTGGGTTATATTTCCAACTTTTCTTCCTGTAGAAGTTATTCCTTAGCTCCTTTCAGGCTTCC
TCTACCTTCATCCCCAGCTCCCAATAGCACTAGTGAATCCTTGAGCAAAACATTTTGTTCATATCTTAAT
GTATATTTTGGTGACAACACATATATGATCACCCCAAACAGGGAACAGGTAGAAATAATAATTTCATTGT
CAAGACTAGCACAGTGCTGGCACGTGGAAAGCATTCAAGACACTTTTTGAAATGAGTAAACATTCAAATT
AGAGGGAGGTGCTTTTATGCCATCTATTAAAGCTAAATAAATAAAATGTATTATTTATTTCTCTATAACA
AGGTAAAACTCTAAAGAGGCAGGCGTTTTCCATTACCATGATTATGTAATATATATTAAATATGTATTGT
ATATCCATGTATCTATAGACATGTCTACATCTCTCTTGATGAATAGAGGACTGCATGCTATACCGAATAA
CTTATATTGGTATGAACAGGTCATCTGGAGAAAATTAGAATAGCAAGACAAAATAAAGTAAGGTAATAAT
TTTTGGAGTATATATATTTAAAACTAAATGCTAATTATGTTAGAATTGGCTTTTATAGTAAAAGTATCTA
ACAGTTAAAGGGGGCTTACTAAGTGATTCAACATGTATGATTTCACTTAATCTTCACAACCACCCCAAGA
GTCAGGTGTTAGTATTGCAATCATTTTACAGATAAGGAAATGAAGCACAGAGGTTTTAGTTAATTCCTTA
AAATAGGGTTGAGCCAGTATTTTTAACCACTTTATCTGATTCAGATTCTGGAATTCACACTTTTCAAAAA
AGTTATTATAAACACACACACACACACAACATAAAATTACCATCTTCATTATTCTTTAGTGTACAGTTTG
GTAGTATTAAGTATATCTGTTGTGCAACAGATCTCCAGAACTTTTCATCTTGTAAAACTAAACCTGAATA
CCAATAAGAGGAATTCCCCATTTCTCTCTTTCCCTAGCCCTTGGCAACCACCATCCTGTTTTCTGTTTCT
ATGACTTTGACTACTTTAGAAACCCCATGTACGTGAATCATACAGTATTGGTCTTTTTGTGACTAGCTTA
TTTCACTTACCATAACGTCCTCAAGGATCATTCATGCTGTAGCATGTGACAGGATTTTCTTCCCTTCTCA
GGCTGCATAATATTCTGTTGTATTTATATACCACATTTTGTTTACCTGTTCATCCCTTGATGGACATTTG
GGTAGCCTCGATCTCTCAGCTATTGTGAATAGTGCGGCTATGAACACGGGTGTGCAAATAGCTCTTTGAG
ACCCCGTTTTCGATTCTTTTGAATATATGTCCAGAAGTAGGATTACTGGATCATTTGGTAATTCTATTTT
TTAATTTTTTCAGGAACTACTATACTGTTTTTCATAGTGGCTCCGCCATTTTACGTTCCCAGCAACACTG
CTAAAGTCTAACCCGCACTTTTAATCACAATATACTGCCTTCTTTTCATAAACTTTAAAAAAGTTAACCT
TCAATCGGTTTCTAATTGCTAGTTTTTTTCTCTCCATAGAACTAGACACAGTTTGGAAATTTTCTCACCC
TTAGGTTGCAACCTTGTTTCCAAGGCTACTTCATGTCATTGGTAATTTCTTTCCAAACTTACCCTAACAG
TAAGAGAGGTACCCATAACATTGGTGGTGTTGATAGAGAACTGTACAAGGCCATGCTCATCCGTGGTAGC
ATTGGAGTAATAGTTTGCTTCATTTCCTCTGATGAATATGACTTTATTTGGTATAGGGACGCCTTTCCCA
TCTACTAGGCGCACCTGAAGATTAAAAGCTGTGGATTAGTTATATTGGTAATAACTAATAGGCACCAAAC
ATATTCATTTATCACATTTTTTAGTGCCTCCTCTATGTTGAACATGGTTCCAGGCACTGAGGACACAGCA
GTGAAAAAAAACGAAGTTTCTTCCATCACAGAGCTTACTGTCTAGTGAAAGAGATAGATGCTAAATAAAT
ATATACATAACATACACTAATTTAGTAGTAATCAATCCTAAGAAGAAAAACAGAGCAGTGTGAAGGGATA
GAGAGTGATAGGGATAATAACAAGAGTGACCTGAAAAATGTCTTCTAGATATTTTGGAAGTGCTGTGTAT
TATTATATATAACTCTTAGAGAGTCACAGAGCACTAGAGTAATATGATAATGAAATATTTTAATCTATTA
ATCTATTAACTAAATTTATTTGTGCCCCAAACACCTATTTTGGAGTGGACCATTAACTTCCTATAGATTA
GTGTCTGAAGTCTCATAAGTGCACAAGTAAACAATTGCCAATACATTGTCCTGTGTGTTTCTCCAGTTGC
CTTAGACATGGTCTCTGCTTCTCAACCTAGATCTTCAGCCTTTTGGAAGGTAGGCAGATTTTATGACACA
CTTCCCATGTGAAAAATATAAAATTGAAAAGAGGCACACAGTATTAAATAAGTTGCCAAATCTAATTTAC
TGCTAATATTGTATTGGCAGTTGAGTAGTCCAGTTCAGATTGTAAAGGTGGCAATTCTTTTTCAGTATAA
GCTACAGTTGGTAGCAGGAAGAACAATAGGCTGACCCCCATCAGTACTCATAATTGATTTACAAAATCTA
AGTTTGCCAGTGAAATGTTGGCTGCATGTACAAAGACAAGAATAGGCACATAATTCTGATTTTCTTCTAG
CTAGAGAGTCTTATGACAAATAGGATATTTAACAGCAATAAAATGTACTTACAAAGTACACTATCTTTCT
GAGAAATTTACAAATGAGCTACACTTTCATTTTAGGAAGTTGAATACATTTTGGTGTCATGACATAACCA
AGCCTTCTAGAATGTACTCCACTTTGTTGAGTCTATGCCTCTTTTACACCCTTCATAGCTGAAATCCTGT
AACATTTACATTAAGAAAATGATACACAGTAAATACACATTGAGGCACATGTAACTGTGATCTCAGACTT
CTAGAGTCATAAAGATCCATTTGCACATCTGCTGACAACAGAAAAATTGTAAGAGAAGATTTTTTTGGTA
GATAACATGAAAATTCATAATTCAAAAATCTGAGAACCTTAAATAGCAGTGTTTTACCCCATGTTCACTG
TTTTAGAAATATACTTGTTATAGAAAAATAGTGTAAATATACTATCCATGAAATAAACATTATTGTAGAA
TCTTTAATACTTCAAAATAAAAATTAAAACCACCTACCCACCTGTTTCCATACAAAGTTAGTGTTAGCAT
CGTAATGAAACTGGTCAGCATGAATTTTGAGATTCTTGTGAGAAAATGTCATAAAAACCTGAGACTGCCT
GGTAAACCATGAGAAGGAGATTGAGTGACTTGTACAATGCTGTTTCAAAAGAAGGGGGGAAAACTCTACT
AATTTTAATAAGGCCTTAGGATAATTACATACATTTCATACACAAATTTACAGAAGAATAAATCTATTTT
TATGTAGTTTTATACCTTTGGTTATACTAATCAAGCCTTGGTGATATTTTATACTTTTGGTTATATTAAA
TGATAACATTAACCAGGCATGGTTTTAGCACAAACCATAACTATTGTGCTAATTAGGTAACAGTACATGG
GTTGATGAGTGAACTGGAAAATACTCCACCTGCCCAAAGAAGGGAATTCCCTGTCGAAAGTGTGAGTCCA
CTTTCACAAATGAGAGTTTGGTTATGGTTCTTGTGATTTCACTGGACTGCCTTCCAGTCAATTCCACCAC
TGAAAAAAGAGAAAAAAATCTGTTATTTTTGGGAAGAATGATGTCTCTAAAATTCTATCACCTCCCCCCA
ACTTACAATTCATTATTTGGCTAAGAAAATCAATGCCTGTTGTGTTTTCTCTTATACCCATGTAGTACAC
AAACCTGTTCCTTCTTCTTGGATCTGGGCCTCAGTGTGAAGTTTCATTTCATACTCCTTCCTCTTCAGCT
GGAAGACCTTGGTTTTTACTTGCTGATAGAAGCAGCCATGGCTGTTTAGCTAAGAAGGGAGAAAATAAAA
TACAAAAATATAATGCATATTATACTAAATAGATCAGTGGTCAGATAACCGGTGTGATTTTTGTGGGGGG
ACAACATCATGTAGGCATTTTCTATGACGAGGACACAATAAATATTCTCTAGCAACTAAATATTAAATTT
CACAACAATATCTCATGTATAATTGACAGATGTATTCCTTGGTATCTGAAATTCCCTAGATATATTGCGA
TAGAAATGTCTTAAAATTTGAGGAGTAATTTTTTTTGTACAAAGGATGCATAATATTTATACATATTTAT
GGGGTACACGAGATATTTTGTTACATGCAGAGAATGTGTAATGATCACATCGCGGGATTTAGGGTGCCTA
CCAACTCAAGTATGTATCATTTCTATGTGTTGGAAATAGTTCAAGTCCTGTCCACTTGCTATTTTGAAAT
ACACAGTACATCTGCTCTTGACCATTAGAACTCCTCATCAAAGTCTGGTTCCTCCTCCATAATATTCAGC
TGTGGCTGGGAAGCGGCCTTCTATATGGGGACTGTGTTTGTCAACTCTCTGGCATCTTGGTGGGGCCATG
TGATAGGTTCTTGTTCACAGAGAGAGCAGAACTGATGGCCTGGCCAGCTAAGGCAATTAAGAGGTGTATG
GTTTTTTCCTTCCTTTGTAGAAGTGAATGCCCATGGAGGCTTTAGATGGCTCAGTGTCTATCGTTCTGAA
ACACTCACAATGGGCAATTACGAGAAATAAATAATTCCCATTGTGCTAAGTTCATGATTTTTTTTGAAAA
ATTACAATAGCCAACATGGAATTCTCTTCTAGATTGTTCTCTTCCTGCGTCAGAAAAATGCTGCAACTCA
CTGCTTTTCAACAATGCCTTTATCGCTATTCTCTAGAAAAAATAGTGTTCAACCTACCTGTCCACTGAAT
TTCTCACAGAAAGCCTGTGAATCTTCACCGTGGCAGTCGGAAGCGTCACTATACTTTCTGCAAATGCTCA
CAGTCACATGTCCAGGGACAGGCTTCCCATATGTGTATCTGTCATGAGAACATTCCCAAAGGAATCAGAG
CAGACACTGAACCTCCCCATTTTCTAGCTATTTATATCTCCCCTTTAGCTACAGTATATTCCCTGTCTGT
ACTTCCCTCTGCTCTCTGCTGGGCTCACACAATATTGAAGACAAGAGTCACTAATGGCTCTTATAGAAAT
CTCCATTGCAACATGCTGAAATTTACATTCTTCTTTTATCATTTCTTTTTTTTCCTCGTTTTTTTTTAGT
TTTATCTTAAAAAAGTCTTTCTTATTATAAAACTTAAACCCGTTCTTAAAAGAGAAACAATACCAGCAAG
ACGAAACAAACAAAACAAAACAGAACAAAAAAAACCCAAACGCCCTCAAGTCTACCTAGGAATACAAACT
ATTAGTACGATAGTGTCTCTTCTTCCATCATCCTCTCCCCATGTGCAGCCATCTCTATATCGAGTTTCAC
TTGTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTTGAGATGGAGTCTCGCTCTGTCGC
CCAGGCTGGAGTGCAGTGGTGCGATCTTGGCTCACTGCAACCTCCACCTCCTGGGTTCATGCCATTCTCC
TGCCTCAGCTTCCCAAGTAGCTGGGACTACAGGCGCTGGCCACCATGCCTGGCTAATTTTTTGTATTTTT
TAGTAGAGACGGGGTTTCACCATGTTAGCCAGGATGGTCTTGATCTCCTGACCTCGTGATCTGCCCACCT
CAGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCACGCCGGGCCTGTTTACTTTTTTACAAAAGT
GGGATTGTGTCGTAAATATGTCATAGACAATTGCTGGGTTTCCAAGTGCATTTGTCTCCTTTCCTATTTG
AGAATGTCCTCTGTATGTCTATTTGCAAGATCACACCAGTTATGAGGAACCAGGAACTTGGCCATCACTG
TGAGACAGAACTGGAGCAGGGGCCTAGCTGAATAGTAGGTGTATTACATGTGTGATCTTTGGACAGGACT
ATACCTGCTCTTCCTGCTACTGCTACTGTGTGCCACCATGGATGGGAACATAAGATCCAGGAAACAAGAC
TTTTCAAGGTTGGAACAGACTGTCTTGAGAAATCACGTTCAGTCTCTTCGTAAAAATGTCAGTGCAGACA
GGTATGTAGACCCGCCTTAGGTGGACTAGTGAGTTAGATGAGATTTCAGTTGTATGCCTATCTCTACAAA
TTCTGAATCTAAGTGATTTTTCCAGTAAGCATGCAAGGTCAGGTAAATGATCTGTTGATGATTGAATTTC
CCCTATAGCCATGTGTTAATTATCTCCCTAATATACGTTTGGTTATTTTTGGTTAAGGCAGAACCAATAC
CCTTCAACACTATCCACCCTTCCCATTTTGTGTGTGTGTGTGTGTGCAGTTTTGTCACTTTCAGAATCAA
TCCTATTAGCATAACCTCTCTAGAAACAGTTTCTTACCTCATGATAGAATAATACTGATAAGAACGTGAA
AGAAAATAAAAATAGAAAAGCAACAGGAGAATAACATTCTACAGATGAGGATGCTGTCAAAGCACTTAAA
ATTTTTGTGTTGCCACTGCTCCCGGAGAGAGTAGTTAAAATATCCCAAATGGTGAGTCTCTTTTAAATAA
TCCCCCACAAAAGATTTTTAAAAAATGAACTCACAGGCCACACACTGATACATTCATCTCTTCTTCCAAG
ATGGTGATTATCTTTGGCACTGTTACTTGTACTTCAAACTTGGGAAGAACTGTTGATTGGTGATAAAGAA
GGTTGGTGATTGGTTTTCAACTTTGGGGGAATTCCTATTTTCAGGTTCCCTGTAACAGTTCCCTAATAAT
ATTTTAGGGCTCTGAAAAGGTAGCTCTGCTCTCCAATCTATTCTTATCTATCCTCCTCTCAAATGAAGAT
TTCAGTTGAGGGACTATGAGAGATCACTGTGTGCTTAATTAATTATGGAAAACTCCATTAAAACAAGAAT
GTTTTAATTTTGGGGGTTGGTATTAAATATTGCTACAGAAAATAACGAAGCTATGTGAAGTCCTATTCAC
AGATCACTGATGTCCTCATTGGACTTAGGTGTAATTAATTCTACTCCAAGCCCAATGTCACCCATGGGAA
ATGGAAAGACTCCAAATGAACTTAAATTCCAGGACCTAAGAGTTTAAATATGAAGAAAAATAATGCTTGA
TGACTTTTCATGATCCATACCAAATTCCTCCACGGTGAAAGGGTGCTCTGTCCTTCCACCTGATTTCTTC
TGTACCACCACCTTGTAGGAGCCCTGGAAGGGCTCTGATGAGAGGGGAAAAGAAAATTGCTTGAGGCCAC
CCTCTAACTGGAAACTCTGCCATTGTGCGATGCGATTTCCTTTGGGATCCTATATGAGTAAATTAATTAT
AACTTACAAAAGCACCTGGAGCATTGGAGCTAATAAAAGATATCTATGGAAACCCTAAGTTATCTACAAA
AAGGTCAAATGGGGTAGTAGTAAAGGGTGAGTAGAGGAGATGAGTTATAGCCATCTAGCTCTATGGGAGT
TTGAAGGCTTCTCCTTTAATGACAAGTTTCTGAGATATTGTAAAAACCTCTGAAATAAGAACATTTTCCC
TATATGTATTGCTTTCCTTTTAATATGGAATGTTTCATGTTGCTTACCTGAATGTATACTAGTGGAATCT
GAAAGACAAAAGAAAAAAGAAGTTTATAATTATTTTCAAATATTCTTAAATCTCATTTATAAGCAAAGCA
GCTAGTATTTGCTAGCATAACAGGGTGAGTATAGTAAAAAATAATTTAATTGTACATTTAAAAATAACTA
AAAGTATAATTGGATTTGTTCGTAACACAAAGAATAAATGTTTGAGGGGATGGGTACTCCATTTATTGAT
ACAGGCATGCAATGCATGATAATAATCATTATCCATGATTGGATAATGATATGGATAATGATAATGATTA
TCATCCATAATCATTATCATGCACTGCATGCCTGTATCAAAATATCTCATGTAACCCATAAATATATATA
CCTGCTATGTTTCCACAAAAATTAAAAACAATAAAAAGTTTAAAAAATCTAAATTAGTTTCATATAGAAT
AATTCCCTCTATAGTGAAATACAGAAATATTCCAGATTAAATTTTATAGAACTTTTCATTAATCTATTTT
AAGCAATTAATAAATAATGTTAAGAACTTACTAGGCCTTCAGCAACAAATATACATGTAAAGTGCCATTT
ACTAAAAATGGATTAACATGTCTTAAGTGCTTATAGCATCCTAGTGAAGATCAATCCTTTGCTATGCAAT
TTTACAGGTTGAGAAATAAACACTTATGTAACTATAAGTAAATATGTTCAGATGTAATCATTAAGATGGG
TCATAGAATTCTTACGTAGTTCTAAGAATGAGGAGGAATGGACATATTTCATTAATAAATTTAGTTTAAT
AAATATTACTTTTAAAAATGAATAAACATTGATAAGAAGCTACTATGAATGTTTATTCATTTTTAAAAAC
TAATCTTTATTAAGTACCTTCTCATGCGCTGTGTATCATTCTAGGTATTGAGAATATAACCACGCACAAA
AGAACAATAAACCATGTTTTAATGGAGCTTATGTTATAATAGAAATAGGCAGATTTTTAAAAATCAATAC
GTATAGAATGGTGGTAAGTGCAAATAGAAAAACAAAGCCAAGTTAGGCTGACAGAGTGATGGGTGTGGTG
CCTCATTTTAGACAGAGGAGTGAAAGTAGAAGCTGGGAGACCACTTTGAAGGTTATTGTAATGATCTTAT
TTAGAGATGACATTGACTAGGACTAGCTTGCAGCAGTAGTTCAGATGATAAGAAATAGTCTGAATATATT
TTAAGCCAACATGATTTTCCAGTGAAGTGGATGTGGGTATGAGAGAAAGAGAAACAAGAACTAGGCCATA
ATCTTTTGTCTTTGGAGCTAGAAGAGAAGAGTTGCCTCTTTTTGAGATAAGAAAATGTGAAGAAGTTAAT
TTGGGAGAGAAAAATGAAGACTTTGGGTTGATGTCTGCATTACAATAGAAAGAACTGTTTCTTATCACAG
ATACCAAGAGTTAGTCTTGAGGAACAAATTAATTACCCTGACTTTCCTTTATAGTGAAGATTTTGGTAGA
TGTGTATAGAAAAAATCTAAATCTTTAAAATGTTTTTTGAGCTTAGGTTCTTTGAGGATTTTTCTGTGTC
TGCTATTGAATGTATCTTTCTAATTGTCCTAATTAAGAACCATCCGAAAAGTAAATTTAATTGTGTGACA
ACTGACTGAGTACCAGCACCAAGACAGAAAGAATTACCTACTTTCTTTACCTGGAATGATGTTTTAGATT
AGGATCTTGTGCTGTTGTAATGCCAGAAGTTACTGTTAATGATACCAGATTCTTCCTCTCCCTGGTCTTC
CCTCAGCACAAAAAACAGGTTCCCAGCCTGTTTATACAGACAATCATTTTATGTAGATAATAGAAAACTC
ACCAACTCATTCAGGGGGTGAAAGTTTTCATCCATGGAGACAACACGAAATTTCACTGAAACAGAAATAT
TTTTCATGAGCCCCCAAACCCAAAGTAGGCCTGTAGGCTGGTAAGACAAGCTATTAAGGAACCAAGATTA
TAGGAACTTTGCCTGGGGAACATCCAGGGGAAGAAGATCTTTCCTTTTTGAAGTTGTCCTGTCTGTAGGC
TTCTTCATACCTGTCTGCCCTGGTTTGTAGATTGATTTGTCTGTCTGGACAAAGACCAGACTGTCCTCGT
TCTTAACCATCACTGTGGTCCGCTTCTTAAATTCTTGGGTTGGTCCTTTCACTTGGACAGTGAGGAACAT
TACCTCCTCATTGGATGAAGACTTTGGGACCTGAAATACAGGACCGATCCTGAAACCCCATTCAGCACCC
GCAGGTCTCCTCCCCTATTTGCTGTTGCACTCTTCCCTGGAGATCTTGCCCTTCTTACTTAACTTCACTC
CCTTGTTCTCAGCAGGGAAAGTTGGCATGGACAGGAATCACTTCTGCCATTTTACAAATGGGGAGACAGG
ACACAAGGTGGAGGAAAATAAATCAGTAAGAGAGGTTGTAAGTGAGATTCACACCTTCATACAGCTCACA
GAAACAGTCTTGATTCAATTATACGCTGAGCTTTACCAGGCTGATATTACATGCTAAAAGGGCATGGTCG
AAGCATGTTTTACAGGCTATGGAAAAAAACCCCGTATTTTACTGACACTAGGCTGTAAGCATCTCACATG
TGGACAACTCTGAAGAGATATTACACCTTTGCTCAGGGTAATTTCTACAATTTTTACTCTTAGAAGTAGT
GTGGAGTGATGTGTTCCTGTCAGTCCACCACGGGTGGCTCATGTTGAGCCTTGGTCTAGTTTGCTTTATT
AATATTTTTTCCATCTTAATTTTAAGAAGTCACATTTTCTTTTTTTTTTTTTCCTTTCTGGCTAATAGGG
TTTCTATGTGATTATTAAGCTGACTTTTAGTTTGCCTGTAAATATTTGTCTCCCATGGCTGGAGAGTCAT
GCATTGCTCCTTAATTTCTATACTTAGTTTGCTACATTTGGATTCCTTCCTGCAGTTCTTACCAACCTCC
CAAAGCCTCATCTGACAGAATACTAGATCCCTATGACCCTGACTAAAAGAACCAAGTATATTAAGTCAAA
CAGCCACACTCACAGCGAAGGCGACACAGTGGAGTACGTCATTCTCCGCCTCCAGGTCAGTGAAGAGGCT
CCTGTTTCCCCTGACAGACTCCAAGGAAGCACTTACAGTCACTGTCTCATTCAGGTAGCTCAGAAGGACA
CAGCCCTTCTCAGTGGTCTCAGTGTGGAGCAGGGAGGGGACCAGAACCATATACTGCCTGGGAATGAGAC
GGTTCAGTTAGAGGAAAGTGAAGGAAGAGAGGCATTGCTATCAACAGCACTTTTTTCCATCATCATAATT
ATCATCATCAGTTCTACACCAAGAGAAGATGTACTGATGAGCATGAAATTTGGCCGTTGAAGGCCATGCA
TAAGAATTATTTCCCTTTTCCCTCACATGCCATGGCAGTGAACATTTTACTTGAGGTAGGTCTTAAACAG
ATTAAAACTTGTAGGCATGCTTCACTTTAAGGAACAATTTGTGAACATCTGAATTCAAATAAAAATATGT
AGTTACATTTGTTCATGTTGTAAAATCTATTTTTACCTTCAAGTTGCTGTAAAAAGTAAGCAAGCTCTCA
GTCATGCGGACATTACAAAAACTAATCAAATTATAGAATTTTCATTAAAATATATATACACACATACATA
CATACACACATTCAGCAGCCCTGTGAAAATTGTATGGTAAGCACTCGCTTCCACTCCACAGATATGGAAT
CTGAGCCTCAAAGAAAGTGAGCCATTACTTCACAGTCTCAGTTGTGGTAAGCAGCTAATAAGGTCTTAAG
AGTGTTACCTAACCATGGATGTTTGCATTTTAAATATTTGCCTTTCAGCTCATGATTAGACAATGGCTCC
ATCCAAAAATGGTCCTCTGGTGATTGACTTTAGACCTTGGTAACTCATGTGCAGTACAGAAACTTTCTCA
GTACCCTGACATGTAATTTAAGATCAACCCTGTAGTTTTTATACATTTTTGCTCACAGAACTCCTAAAAT
AATTTTTGGACTCTGTGCACTCCTTACATATTTTCAAGTAAACATATTTTTATCATGATTTTAAGTAATA
GCAAAAGATATTATTTTTGATGATATTTTAAATTAATACTTAGATTACTTTTACAATTTTCTCATGAATA
ATAAACACTGTAGTATAAGATACCTACTATCACTATTTAAAAGTACATTAAAAAATTCTTTTAATGGTCT
GATATTTAATATCTTTCTCTTCTTTTTTCCTTTTTGAATTTGAATTTCCATGCCAATTACCATACAGAAA
TTTATCCTAAATTTTTATATTTCAAAAAATGTTGTGAATTATTCTTACTTCTTTATTGTCAAGCATCTAT
ACATATACGTATGTATACTTATGTTCACATATATACATATATGAATACATATACATAAATACATATATAT
GTAACATATGTGGGTAGGTAAATTTAACTTTAACTCCTCTTTTAAATAGAATGTAACCATAAATTTATAA
ATATTAAACATTTCCTTCTGACTGAGCTATGTTCAAAAATACTTGTATATAACTGATCAAAACAAAATAA
ATACAAAGTATGATTCATACATATTAGATATAAAATTAAAATACTTTTGAAGCACATCTTTAATGAGAAT
GATGAGCTGTTTTTTCCCCCAGTGAATTTATGCATCCATGGATTGCAAGAATTAAACAACATTAATTCTG
TTACTATTTTTGTTTTGTGTAGCTATAAGTGCTAAGAAGAATGGCTCACATAAAAGTAAATAAATGGCAG
GTAAAACAATTGCATCATTGTTACCACTTCTTGCAACTTCTGCATTACATGCCAAAAATCACCTAGTACT
CTATTATCAAGAATCCCTTCTCATCACTCATCAGCTGGTATTTCCTTCAGTTCCTCCTTCAGTTGTGTTG
AAACAAAGAATTCATCACCACCTCATCTGCAAAAGGATTTCTCTTCTGACATTAGAGTCCCTTGCTTTTT
CAATATCAACACCAGTATTTCAAATTGTTCCTTTATTTGGCACTCTATAGATTTTTATACTCCAGGGCAT
TGTTCCATGTTTGGTTGTGGGAGAGAATTGTCTTTATTTTTATAAAATAGAAAATGGACCCTTGAGAAAG
AGGAAATAAGAAAAGATAAATAGCATGGTCTCAAGTAGATCAATATGAATGTGAATATCTAAAATTTATT
CTTTTAAAAAGCTAAAAATTTCTGACACCCCTTAGGAAGGCTTTGCATATTAGAGCTTCAGAGAGTTGGG
GAAGAATGATTAAAAGTAAGCAAGTAATGAGTAAACTAGATTTGTAAAATCTGGAAGGAATCTTAGAGAT
AAGAAGATGACAGTATCATAGGAAAGAAAAAGGAATGATATAAAGAAAAATCTGCAATAAATGAAGGACT
CTAGGTTCATGCTTCACGCTCTCTGTGTGGAACTCACGGTTTTCCAGAGACTGAGGCGTCTGTGGGCAGG
AGGACCAAGAGGAGAAGAACCAGACTTGGATGAAGGAGTTTGTTCTTCCCCATGTTGCAGAAAGAAGGAG
CTGGAGGAGAACAGACTGTATTGTACCCTACTCCCTACAATCCATCTGGTCCCAAACACTTCCCAAAGCA
ACTGGGCTTTATGCTGCTCTGTGTG

Protein Sequence : Show Sequence

>gi|66932947|ref|NP_000005.2| alpha-2-macroglobulin precursor [Homo sapiens]
MGKNKLLHPSLVLLLLVLLPTDASVSGKPQYMVLVPSLLHTETTEKGCVLLSYLNETVTVSASLESVRGN
RSLFTDLEAENDVLHCVAFAVPKSSSNEEVMFLTVQVKGPTQEFKKRTTVMVKNEDSLVFVQTDKSIYKP
GQTVKFRVVSMDENFHPLNELIPLVYIQDPKGNRIAQWQSFQLEGGLKQFSFPLSSEPFQGSYKVVVQKK
SGGRTEHPFTVEEFVLPKFEVQVTVPKIITILEEEMNVSVCGLYTYGKPVPGHVTVSICRKYSDASDCHG
EDSQAFCEKFSGQLNSHGCFYQQVKTKVFQLKRKEYEMKLHTEAQIQEEGTVVELTGRQSSEITRTITKL
SFVKVDSHFRQGIPFFGQVRLVDGKGVPIPNKVIFIRGNEANYYSNATTDEHGLVQFSINTTNVMGTSLT
VRVNYKDRSPCYGYQWVSEEHEEAHHTAYLVFSPSKSFVHLEPMSHELPCGHTQTVQAHYILNGGTLLGL
KKLSFYYLIMAKGGIVRTGTHGLLVKQEDMKGHFSISIPVKSDIAPVARLLIYAVLPTGDVIGDSAKYDV
ENCLANKVDLSFSPSQSLPASHAHLRVTAAPQSVCALRAVDQSVLLMKPDAELSASSVYNLLPEKDLTGF
PGPLNDQDDEDCINRHNVYINGITYTPVSSTNEKDMYSFLEDMGLKAFTNSKIRKPKMCPQLQQYEMHGP
EGLRVGFYESDVMGRGHARLVHVEEPHTETVRKYFPETWIWDLVVVNSAGVAEVGVTVPDTITEWKAGAF
CLSEDAGLGISSTASLRAFQPFFVELTMPYSVIRGEAFTLKATVLNYLPKCIRVSVQLEASPAFLAVPVE
KEQAPHCICANGRQTVSWAVTPKSLGNVNFTVSAEALESQELCGTEVPSVPEHGRKDTVIKPLLVEPEGL
EKETTFNSLLCPSGGEVSEELSLKLPPNVVEESARASVSVLGDILGSAMQNTQNLLQMPYGCGEQNMVLF
APNIYVLDYLNETQQLTPEIKSKAIGYLNTGYQRQLNYKHYDGSYSTFGERYGRNQGNTWLTAFVLKTFA
QARAYIFIDEAHITQALIWLSQRQKDNGCFRSSGSLLNNAIKGGVEDEVTLSAYITIALLEIPLTVTHPV
VRNALFCLESAWKTAQEGDHGSHVYTKALLAYAFALAGNQDKRKEVLKSLNEEAVKKDNSVHWERPQKPK
APVGHFYEPQAPSAEVEMTSYVLLAYLTAQPAPTSEDLTSATNIVKWITKQQNAQGGFSSTQDTVVALHA
LSKYGAATFTRTGKAAQVTIQSSGTFSSKFQVDNNNRLLLQQVSLPELPGEYSMKVTGEGCVYLQTSLKY
NILPEKEEFPFALGVQTLPQTCDEPKAHTSFQISLSVSYTGSRSASNMAIVDVKMVSGFIPLKPTVKMLE
RSNHVSRTEVSSNHVLIYLDKVSNQTLSLFFTVLQDVPVRDLKPAIVKVYDYYETDEFAIAEYNAPCSKD
LGNA

Molecule Role : Vaximmutor
Related Vaccine(s): Actinobacillus pleuropneumoniae HS93Tox-/pIG-T1K vectored vaccine

2. Ighg1

Gene Name : Ighg1
Sequence Strain (Species/Organism) : Mus musculus
NCBI Gene ID : 16017
Genbank Accession : AC160982
Molecule Role : Vaximmutor
Related Vaccine(s): A. pleuropneumoniae DNA vaccine pcDNA-apxIA/pcDNA-apxIIA

3. Ighv1-9

Gene Name : Ighv1-9
Sequence Strain (Species/Organism) : Mus musculus
NCBI Gene ID : 668478
Genbank Accession : AC073561
Taxonomy ID : 10090
Chromosome No : 12
Gene Starting Position : 114583568
Gene Ending Position : 114583861
Protein Name : immunoglobulin heavy variable V1-9
Protein Note : Also known as Igg2a; Gm16697

DNA Sequence : Show Sequence

>gi|372099098:114583568-114583861 Mus musculus strain C57BL/6J chromosome 12, GRCm38 C57BL/6J
GTCTTGCACAGTAATAGATGGCAGAGTCCTCAGTTGTCAGGCTGCTGAGTTGCATGTAGGCTGTGTTGGA
GGATGTATCTGCAGTGAATGTGGCCTTGCCCTTGAACTTCTCATTGTAGTTAGTACTACCACTTCCAGGT
AAAATCTCTCCAATCCACTCAAGGCCATGTCCAGGCCTCTGCTTTACCCACTCTATCCAGTAGCCAGTGA
ATGTGTAGCCAGTAGCCTTGCAGGAAAGCTTCACTGAGGCCCCAGGCTTCATCAGCTCAGCTCCAGACTG
CTGCAGCTGAACCT

Molecule Role : Vaximmutor
Related Vaccine(s): A. pleuropneumoniae DNA vaccine pcDNA-apxIA/pcDNA-apxIIA

IV. Vaccine Information

1. A. pleuropneumoniae apfA vaccine

a. Type:

Subunit vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Baboon

d. Host Species as Laboratory Animal Model:

Mice

e. Gene Engineering of apfA

Type: Recombinant protein preparation
Description: Purified recombinant ApfA elicited an elevated humoral immune response and conferred robust protection against challenges with A. pleuropneumoniae serovar 1 strain 4074 and serovar 7 strain WF83 in mice (Zhou et al., 2013).
Detailed Gene Information: Click here.

f. Immunization Route

Intraperitoneal injection (i.p.)

2. A. pleuropneumoniae ApxIa and ApxIIa protein vaccine

a. Vaccine Ontology ID:

VO_0011384

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

A. pleuropneumoniae ApxIa and ApxIIa

e. Gene Engineering of apxIIA

Type: Recombinant protein preparation
Description: The apxIIA gene was cloned from A. pleuropneumoniae serotype 5 isolated from the lungs of Korean pigs with pleuropneumonia. For the oral vaccine, S. cerevisiae expressing ApxIA antigen as well as the ApxIIA antigen were prepared (Shin et al., 2007).
Detailed Gene Information: Click here.

f. Gene Engineering of apxIA

Type: Recombinant protein preparation
Description: The apxIA gene was cloned from A. pleuropneumoniae serotype 5 isolated from the lungs of Korean pigs with pleuropneumonia. For the oral vaccine, S. cerevisiae expressing ApxIA antigen as well as the ApxIIA antigen were prepared (Shin et al., 2007).
Detailed Gene Information: Click here.

g. Adjuvant:

VO ID: VO_0000133

h. Adjuvant:

VO ID: VO_0000139

i. Vector:

Saccharomyces cerevisiae

j. Immunization Route

Oral immunization

k. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Briefly, 15 mice per group were subcutaneously injected with 100 µg of protein extract after emulsifying with complete Freund's adjuvant (Sigma, USA). This was then followed by a boost immunization with the same amount of antigens after emulsifying with incomplete Freund's adjuvant (Sigma, USA) at 2 weeks after the initial immunization. The final immunization was performed in the same manner at 2 weeks after the boost immunization. All groups were immunized orally through an oral gavage with 4 doses of Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) at 10-day intervals (Shin et al., 2007).
Challenge Protocol: Mice in each group were challenged by intraperitoneal injection of a field isolate of A. pleuropneumoniae serotype 5 at 1.45 × 10^6 CFU (minimal lethal dose, MLD) in 10 days after their final immunization, and were then monitored every 6 h for up to 72 h (Shin et al., 2007).
Efficacy: After the challenge, the mice in group E had a significantly lower infectious burden and a higher level of protection than the mice in the other groups (p < 0.05) (Shin et al., 2007).

3. A. pleuropneumoniae ApxIA protein vaccine

a. Vaccine Ontology ID:

VO_0011356

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

ApxIA (Shin et al., 2007)

e. Gene Engineering of apxIA

Type: Recombinant protein preparation
Description: The apxIA gene was cloned from A. pleuropneumoniae serotype 5 isolated from the lungs of Korean pigs with pleuropneumonia. For the oral vaccine, S. cerevisiae expressing ApxIA antigen were prepared (Shin et al., 2007)
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0000139

g. Vector:

Saccharomyces cerevisiae (Shin et al., 2007)

h. Immunization Route

Oral immunization

i. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Briefly, 15 mice per group were subcutaneously injected with 100 µg of protein extract after emulsifying with complete Freund's adjuvant (Sigma, USA). This was then followed by a boost immunization with the same amount of antigens after emulsifying with incomplete Freund's adjuvant (Sigma, USA) at 2 weeks after the initial immunization. The final immunization was performed in the same manner at 2 weeks after the boost immunization. All groups were immunized orally through an oral gavage with 4 doses of Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) at 10-day intervals (Shin et al., 2007).
Challenge Protocol: Mice in each group were challenged by intraperitoneal injection of a field isolate of A. pleuropneumoniae serotype 5 at 1.45 × 106 CFU (minimal lethal dose, MLD) in 10 days after their final immunization, and were then monitored every 6 h for up to 72 h (Shin et al., 2007).
Efficacy: The immunogenicity of the rApxIA antigen derived from the yeast was confirmed by a high survival rate and an ApxIA-specific IgG antibody response (p <0.01) (Shin et al., 2007).

4. A. pleuropneumoniae DNA vaccine pcDNA-apxIA/pcDNA-apxIIA

a. Vaccine Ontology ID:

VO_0004544

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of apxIA

Type: DNA vaccine construction
Description:
Detailed Gene Information: Click here.

f. Gene Engineering of apxIIA

Type: DNA vaccine construction
Description:
Detailed Gene Information: Click here.

g. Vector:

pcDNA3.1 (Chiang et al., 2009)

h. Immunization Route

Intramuscular injection (i.m.)

i. Mouse Response

Immune Response: Significant humoral immune responses were induced by this DNA vaccine through intramuscular immunization. The IgG subclass (IgG1 and IgG2a) analysis indicates that divalent DNA vaccine induces both Th1 and Th2 immune responses (Chiang et al., 2009).
Efficacy: Animals immunized with divalent vaccine demonstrated 70% survival after challenge with a dose of 5 × 108 CFU of A. pleuropneumoniae serotype 1 ten days after 2nd boost. Survival was significantly higher than that of the negative control groups (P < 0.05). No protective efficacy was observed for pcDNA3.1 vector immunization group and PBS control group and all mice were died within 24 h (Chiang et al., 2009).
Host Gene Response of Ighg1
- Gene Response: Both IgG1 and IgG2a responses were induced by divalent DNA vaccine, with IgG1 slightly higher than IgG2a. The levels of IgG1 and IgG2a were also significant compared with the negative control groups (Chiang et al., 2009).
- Detailed Gene Information: Click here.
Host Gene Response of Ighv1-9
- Gene Response: Both IgG1 and IgG2a responses were induced by divalent DNA vaccine, with IgG1 slightly higher than IgG2a. The levels of IgG1 and IgG2a were also significant compared with the negative control groups (Chiang et al., 2009).
- Detailed Gene Information: Click here.

5. A. pleuropneumoniae HbpA vaccine

a. Type:

Subunit vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Baboon

d. Host Species as Laboratory Animal Model:

Pigs

e. Gene Engineering of hbpA

Type: Recombinant protein preparation
Description: he coding sequence of candidate genes were amplified from the genomic DNA of A. pleuropneumoniae JL03. The PCR products were cloned into pET28a and transformed into E. coli DH5α. Positive clones were transformed into E. coli BL21 (DE3) for expression. HbpA induced relatively higher levels of antibody titers compared with the other proteins, reaching 40% protection in mice when challenged with A. pleuropneumoniae JL03(Chen et al., 2012).
Detailed Gene Information: Click here.

f. Immunization Route

Intramuscular injection (i.m.)

6. A. pleuropneumoniae HS93C-Ampr

a. Vaccine Ontology ID:

VO_0011385

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Antigen

A. pleuropneumoniae ApxII-activating protein, ApxIIC

e. Gene Engineering of ApxIIC

Type: Gene mutation
Description: Site-specific mutagenesis of the apxIIC gene utilized the recombination plasmid pEP-CAmpr. Cesium chloride-purified pEP-CAmpr DNA was isolated from E. coli and linearized with ClaI. Following digestion, the DNA was purified by phenol-chloroform extraction and ethanol precipitated. A total of 3 μg of linearized DNA was electroporated (0.2-cm-diameter cuvettes; 400 Ω; 1.25 kV) into A. pleuropneumoniae HS93 (serovar 7, ApxII) (Prideaux et al., 1999).
Detailed Gene Information: Click here.

f. Vector:

A. pleuropneumoniae serovar 7 strain HS93

g. Immunization Route

Intramuscular injection (i.m.)

h. Pig Response

Vaccination Protocol: Nine 6-week-old pigs received 109 CFU of the A. pleuropneumoniae vaccine strain in 1 ml of growth medium, via intranasal inoculation on day 0, while nine control pigs received 1 ml of BHI. The vaccine was prepared by inoculating 10 ml of BHI-NAD (10 μg/ml) with a single colony of the vaccine strain and growing with shaking at 37°C until an OD600 of 0.8 was reached. The vaccination schedule was repeated on day 14. On day 28, the nine vaccinated and nine control pigs were divided into groups of six and three (Prideaux et al., 1999).
Challenge Protocol: Two groups of six pigs (i.e., vaccinated and unvaccinated) were challenged with 2 × 10^9 A. pleuropneumoniae HS25 (serovar 1) in 2 ml of growth medium via the intranasal route, while the groups of three were given 2 ml of BHI broth in a similar manner. The challenge strain was prepared by inoculating a single colony of HS25 into BHI-NAD (10 μg/ml) and growing until an OD600 of 0.8 was reached. At this time the viable count was 10^9 CFU/ml. At 5 days postchallenge, pigs were euthanized, and the number and severity of lung lesions were recorded (Prideaux et al., 1999).
Efficacy: Pigs vaccinated with live HS93C- Ampr via the intranasal route were protected against a cross-serovar challenge with a virulent serovar 1 strain of A. pleuropneumoniae (Prideaux et al., 1999).

7. A. pleuropneumoniae OmpW vaccine

a. Type:

Subunit vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Baboon

d. Host Species as Laboratory Animal Model:

Pigs

e. Gene Engineering of ompW

Type: Recombinant protein preparation
Description: The coding sequence of candidate genes were amplified from the genomic DNA of A. pleuropneumoniae JL03. The PCR products were cloned into pET28a and transformed into E. coli DH5α. Positive clones were
transformed into E. coli BL21 (DE3) for expression. OmpW induced relatively higher levels of antibody titers compared with the other proteins, and reached 40% protection in mice. All OmpW-vaccinated pigs
except one developed very mild disease(Chen et al., 2012).
Detailed Gene Information: Click here.

f. Immunization Route

Intramuscular injection (i.m.)

8. A. pleuropneumoniae TonB2 vaccine

a. Type:

Live, attenuated vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Baboon

d. Host Species as Laboratory Animal Model:

Mice

e. Gene Engineering of tonB2

Type: Recombinant protein preparation
Description: The tonB2 gene was cloned from Actinobacillus pleuropneumoniae JL01 (serovar 1) and expressed as a glutathione-S-transferase (GST) fusion protein in Escherichia coli BL21(DE3). Purified soluble GST-TonB2 was assessed for its ability to protect BALB/c mice against A. pleuropneumoniae infection. Mice were vaccinated with GST-TonB2 subcutaneously and challenged intraperitoneally with either ~4.0 × 10^5 colony-forming units (CFU) or ~1.0 × 10^6 CFU of A. pleuropneumoniae 4074 (Liu et al., 2011).
Detailed Gene Information: Click here.

f. Immunization Route

subcutaneous injection

9. Actinobacillus pleuropneumoniae apxIA mutant vaccine

a. Vaccine Ontology ID:

VO_0002766

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Gene Engineering of apxIA

Type: Gene mutation
Description: This apxIA mutant is from Actinobacillus pleuropneumoniae (Xu et al., 2006).
Detailed Gene Information: Click here.

e. Immunization Route

intranasal immunization

f. Pig Response

Persistence: An apxIA mutant is attenuated in pigs (Xu et al., 2006).
Efficacy: An apxIA mutant offered a level of cross-serovar protection against A. pleuropneumoniae infection in pigs (Xu et al., 2006).

g. Mouse Response

Persistence: An apxIA mutant is attenuated in mice (Xu et al., 2006).
Efficacy: An apxIA mutant offered a level of cross-serovar protection against A. pleuropneumoniae infection in mice (Xu et al., 2006).

10. Actinobacillus pleuropneumoniae ApxIC mutant vaccine

a. Vaccine Ontology ID:

VO_0002767

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Gene Engineering of ApxIC

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

To construct an avirulent mutant strain by inactivation of ApxI toxin, the apxIC gene of A. pleuropneumoniae serovar 10 was inactivated by inserting a chloramphenicol resistance gene cassette into the downstream XhoI site of the apxIC gene for constructing the transfer plasmid. The transfer plasmid was introduced into the electrocompetent A. pleuropneumoniae serovar 10 for homologous recombination by electroporation. The mutant strain was obtained and identified by PCR and Southern blotting (Xu et al., 2007).

f. Immunization Route

intranasal immunization

g. Mouse Response

11. Actinobacillus pleuropneumoniae apxIIC and apxIVA double deletion mutant vaccine

a. Type:

Live, attenuated vaccine

b. Status:

Research

c. Gene Engineering of ApxIIC

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

d. Gene Engineering of ApxIVA

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

Plasmid pENT1 was used to introduce the ΔapxIVA deletion into A. pleuropneumoniae single mutant ΔapxIIC via the single-step transconjugation system. The colonies with the correct PCR profile were confirmed by Southern blot and sequencing assays (Liu et al., 2007).

f. Immunization Route

Intraperitoneal injection (i.p.)

g. Mouse Response

Host Strain: BALB/c
Persistence: The LD50 data shown that the double mutant ΔapxIICΔapxIVA was attenuated by three-fold, compared with the single mutant HB04C− (Liu et al., 2007).
Efficacy: Two weeks after secondary immunization, all mice were challenged with 10 LD50 of homologous (WF83) (6.0 × 107) and heterologous (1.8 × 106) (S4074) virulent A. pleuropneumonaie by intraperitoneal route. There was no mouse died in groups 1 and 2, which shown a protection efficiency of 100% against homologous challenge (Liu et al., 2007).

12. Actinobacillus pleuropneumoniae apxIIIB and apxIIID double mutant vaccine

a. Type:

Live, attenuated vaccine

b. Status:

Research

c. Gene Engineering of apxIIIB

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

d. Gene Engineering of apxIIID

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

An apxIIIBD mutant (1536∆B∆D) was selected and the correct mutation was verified by PCR using three primer pairs. The X3BD-F2 and X3BD-R2 primer pair was designed to produce products of 3720 and 4365 bps from the wild-type 1536 and 1536∆B∆D genomes, respectively (Park et al., 2009).

f. Immunization Route

intranasal immunization

g. Pig Response

Persistence: The LD50 of 1536∆B∆D in mice was 6.9 x 10^8 CFU, while that of the wild-type was 4.0 x 10^8 CFU, showing that the mutation of the apxIIIBD genes attenuates the lethality of A. pleuropneumoniae in mice (Park et al., 2009).
Efficacy: To evaluate the ability of the mutant 1536∆B∆D strain to protect mice against lethal challenge, mice were immunized with 1536∆B∆D twice and challenged with a lethal dose of wild-type A. pleuropneumoniae 1536. Eight of the nine mice immunized with 1536∆B∆D survived for more than 72 hr after lethal challenge (89% protection), while all eight of the unimmunized mice died by 72 hr after challenge (Park et al., 2009).

13. Actinobacillus pleuropneumoniae HS93Tox-/pIG-T1K vectored vaccine

a. Vaccine Ontology ID:

VO_0004607

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mice

e. Vector:

A mutant form of Actinobacillus pleuropneumoniae serovar strain HS93, known as HS93Tox- which lacks the genes ApxA (structural toxin) and ApxC (post-translational activating protein) (Prideaux et al., 1998).

f. Preparation

The HS93Tox- mutant of the serovar 7 strain of Actinobacillus pleuropneumoniae lacks the genes encoding the toxin ApxA and the post-translational activating protein ApxC, but still has genes required for secretion, making it a good vector. A plasmid vector was created to express the ApxA gene inside the HS93Tox- mutant of A. pleuropneumoniae, so that the bacterium acts as a vector for its own natural toxin (Prideaux et al., 1998).

g. Immunization Route

Intramuscular injection (i.m.)

h. Virulence

Because the toxin has been attenuated, this greatly decreases the potential virulence of the vaccine.

i. Description

The HS93Tox-/pIG-T1K vector strain, using an Actinobacillus pleuropneumoniae to express the AxpA gene, was shown to protect mice against Actinobacillus pleuropneumoniae challenges (Prideaux et al., 1998). ApxA gene encodes an A. pleuropneumoniae structural toxin (Prideaux et al., 1998).

j. Mouse Response

Vaccine Immune Response Type: VO_0001030
Immune Response: The inoculation with HS93Tox-/pIG-T1K induced antibodies specific to the Apx gene, and this response was boosted when the mice were re-inoculated (Prideaux et al., 1998).
Challenge Protocol: The mice inoculated with HS93Tox-/pIG-T1K strain expressing the toxin gene and the HS93Tox- not expressing the toxin gene were challenged with homologous wild-type serovar 7 and heterologous serovar 1 strains of A. pleuropneumoniae (Prideaux et al., 1998).
Efficacy: The mice vaccinated with the HS93Tox-/pIG-T1K strain were protected against both the serovar 7 and serovar 1 challenges, but the mice only inoculated with the HS93Tox- strain not expressing the gene for the AxpA toxin received no protection against the heterologous serovar 1 challenge (Prideaux et al., 1998).

14. Actinobacillus pleuropneumoniae ureC and apxIIA double mutant deletion vaccine

a. Type:

Live, attenuated vaccine

b. Status:

Research

c. Gene Engineering of apxIIA

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

d. Gene Engineering of ureC

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

To construct the A. pleuropneumoniae serotype 2 isogenic mutant, 12 clinical isolates were tested initially with respect to their amenability to genetic manipulation via conjugation and cointegration of pBMKUΔ1 (Tonpitak et al., 2002).

f. Immunization Route

aerosol immunization

g. Pig Response

Persistence: In all pigs, an immune response could be detected in the detergent extract enzyme-linked immunosorbent assay (ELISA), and only in the wild-type group six of seven pigs showed elevated levels (>10 ELISA units [EU]) in the ApxIIA ELISA 3 weeks after challenge. These results showed that the A. pleuropneumoniae double-mutant strain is highly attenuated and that the group infected with the mutant strain can be discriminated from the wild-type-infected group based on the ApxIIA ELISA (Tonpitak et al., 2002).
Efficacy: A single aerosol application of the attenuated double mutant resulted in protection from clinical disease comparable to that obtained with two applications by using a conventional bacterin vaccine. In addition, immunized pigs were protected significantly from colonization of the lungs (Tonpitak et al., 2002).

15. APP HflX vaccine

a. Type:

Subunit vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Baboon

d. Host Species as Laboratory Animal Model:

Mice

e. Immunization Route

subcutaneous injection

f. Description

(Zhang et al., 2016)

16. HS93Tox-/pIG-T1K

a. Vaccine Ontology ID:

VO_0004637

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Gene Engineering of apxIA

Type: Recombinant vector construction
Description: HS93Tox-/pIG-T1K, expresses the Apx structural protein in a non-activated form (Prideaux et al., 1998).
Detailed Gene Information: Click here.

f. Preparation

HS93Tox-/pIG-T1K, expresses the Apx structural protein in a non-activated form (Prideaux et al., 1998).

g. Immunization Route

Intramuscular injection (i.m.)

h. Mouse Response

Vaccination Protocol: Mice were vaccinated with alive strain of HS93Tox-/pIG-T1K (Prideaux et al., 1998).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: Mice were challenged with a wild-type serovar 7, and a serovar 1 strain (Prideaux et al., 1998).
Efficacy: Live vaccination of mice with HS93Tox-/pIG-T1K offered protection against homologous wild-type serovar 7 challenge, and also heterologous challenge with a serovar 1 strain (Prideaux et al., 1998).

17. mixture of Salmonella strains delivering ApxIA, ApxIIA, ApxIIIA and OmpA of A. pleuropneumoniae

a. Type:

Recombinant vector vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Mouse

d. Host Species as Laboratory Animal Model:

Mice

e. Gene Engineering of apxIA

Type: Recombinant vector construction
Description: An attenuated Salmonella Typhimurium was used to express ApxIA (Hur et al., 2016).
Detailed Gene Information: Click here.

f. Gene Engineering of ompA

Type: Recombinant vector construction
Description: An attenuated Salmonella Typhimurium was used to express OmpA (Hur et al., 2016).
Detailed Gene Information: Click here.

g. Gene Engineering of apxIIA

Type: Recombinant vector construction
Description: An attenuated Salmonella Typhimurium was used to express ApxIIA (Hur et al., 2016).
Detailed Gene Information: Click here.

h. Gene Engineering of apxIIIA

Type: Recombinant vector construction
Description: An attenuated Salmonella Typhimurium was used to express ApxIIIA (Hur et al., 2016).
Detailed Gene Information: Click here.

i. Immunization Route

intranasal immunization

j. Description

(Hur et al., 2016)

k. Mouse Response

Immune Response: The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.(Hur et al., 2016)

18. PleuroStar APP

a. Tradename:

PleuroStar APP

b. Manufacturer:

Novartis Animal Health

c. Vaccine Ontology ID:

VO_0000889

d. Type:

Recombinant vector vaccine

e. Status:

Licensed

f. Host Species for Licensed Use:

Pig

g. Immunization Route

Intramuscular injection (i.m.)

h. Description

Recombinant ApxII, TbpB, CysL, OmlA(1), and OmlA(2) proteins (Van et al., 2001)

19. Porcilis APP

a. Tradename:

Porcilis APP

b. Manufacturer:

Intervet

c. Vaccine Ontology ID:

VO_0001158

d. Type:

Recombinant vector vaccine

e. Status:

Licensed

f. Host Species for Licensed Use:

Pig

g. Immunization Route

Intramuscular injection (i.m.)

h. Description

Extracted ApxI, ApxII, ApxIII, and outer membrane proteins (Chiers et al., 1998).

20. rS.C-APP-ApxI/ApxII

a. Vaccine Ontology ID:

VO_0004785

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Gene Engineering of apxIA

Type: Recombinant vector construction
Description: S. cerevisiae expressing either ApxI or ApxII (Shin et al., 2013).
Detailed Gene Information: Click here.

f. Gene Engineering of apxIIA

Type: Recombinant vector construction
Description: S. cerevisiae expressing either ApxI or ApxII (Shin et al., 2013).
Detailed Gene Information: Click here.

g. Preparation

The surface-displayed ApxIIA#5 expressing S. cerevisiae and the ApxIA expressing S. cerevisiae (Shin et al., 2013).

h. Immunization Route

Oral immunization

i. Pig Response

Vaccination Protocol: Three groups were designated as the untreated pigs (n = 5, control), the pigs fed with the vector-only S. cerevisiae (n = 5, vector control), and the experimental pigs fed with the ApxIA expressing S. cerevisiae and the surface-displayed ApxIIA#5 expressing S. cerevisiae at a time (n = 10, vaccinated group), respectively. The yeast vaccines were followed by three-time administrations with ApxIA (1.5 × 109 CFU) and ApxIIA (1.5 × 109 CFU) with one week interval (Shin et al., 2013).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: The pigs were challenged intranasally one week after final vaccination with a dose (1.5 × 10^9 CFU) of A. pleuropneumoniae serotype 5 Korean isolate from a pig with porcine pleuropneumonia (Shin et al., 2013).
Efficacy: The vaccinated pigs showed higher specific IgG- and IgA-related antibody activities than the non-treated control and vector control pigs. Additionally, the induced immune responses were found to protect pigs infected with A. pleuropneumoniae according to the analysis of clinical signs and the gross and microscopic pulmonary lesions (Shin et al., 2013).

21. rS.C-APP-ApxIIA

a. Vaccine Ontology ID:

VO_0004786

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Gene Engineering of apxIIA

Type: Recombinant vector construction
Description: A neutralizing epitope fragment of ApxIIA toxin was expressed on the cell surface of Saccharomyces cerevisiae (Kim et al., 2010).
Detailed Gene Information: Click here.

f. Preparation

(Kim et al., 2010) A neutralizing epitope fragment of ApxIIA toxin was expressed and immobilized on the cell surface of Saccharomyces cerevisiae for efficient vaccine development.

g. Immunization Route

Oral vaccination

h. Mouse Response

Vaccination Protocol: Oral immunization was preceded by overnight fasting of the mice (water was provided ad libitum). Freshly harvested 2.5 x 10^7 or 2.5 x 10^8 cells were dissolved into 1ml of 0.9% saline and orally administered at 200 µl/mouse through an oral gavage at 10 day intervals, 4 times (Kim et al., 2010).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: The immunized mice were injected intraperitoneally with 200 ml of an A. pleuropneumoniae preparation (about 1 x 10^8 CFU) or buffer control 10 days after the final immunization (Kim et al., 2010).
Efficacy: The mice fed the recombinant epitope-expressing yeast were protected from injection of a lethal dose of A. pleuropneumoniae (Kim et al., 2010).

V. References

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