Fungal Allergen Genes

Allergy is a disorder of the immune system often also referred to as atopy. Allergic reactions occur to environmental substances known as allergens; these reactions are acquired, predictable and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma, food allergies, and reactions to the venom of stinging insects such as wasps and bees.
Mild allergies like hay fever are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness, and runny nose. Allergies can play a major role in conditions such as asthma. In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening anaphylactic reactions.

The causative agents of allergy are commonly eukaryotic proteins apparently mostly restricted to a number of functional classes. Identification of the genes encoding allergens is an essential first step in characterisation of the allergen and its epitopes and for studies involving diagnosis and cross-reaction where pure protein preparations are necessary. Much past and current effort has gone into discovering allergen gene sequences to define the nature of allergenic proteins and allow manipulation of allergen gene sequences for definition of epitopes, production of component resolved diagnostics or to direct design of a variety of immunotherapeutics. Fungi are estimated to sensitise ~20% of the atopic population although they may not be always the sole or causative agent. One important allergenic fungus is Aspergillus fumigatus with 20 described allergens. This fungus is also important as a pathogen of immunocompromised individuals and as a complicating allergenic factor in asthmatics. Although ~20 allergens have been described in A. fumigatus only four are known in A. oryzae, 5 in A. niger and a further 2 in A. flavus [www.allergome.org]. A possible allergen Asp ni 2 (previously Asp nd1) has also been described in A. nidulans. Other species of Aspergillus known to be allergenic such as A. clavatus, A. versicolor, A. sydowii and A. ochraeus have no allergens yet described. The genomes of several Aspergillus species have recently been sequenced and presented on this site under Aspergillus Genomes. Fungi produce ~90 allergens from a total of ~750 published in databases. A description of Aspergillus allergens including data on IgE reactivity and occurrence of allergy to specific proteins as presented here[link to website fungal allergens article]

The table below shows a list of known and predicted allergens from A.fumigatus with links to both the Aspergillus Genomes page for a particular gene (e.g. AFUA_5G02330) and to the SDAP allergen batabase for a particular allergen name (e.g. Asp f 1). A number of related fungal allergens that are of the same gene type are listed on the right of the table and the bottom half of the table shows genes in A.fumigatus that are homologous to known allergens from other sources but that have not yet been formally described as allergens in A.fumigatus

Aspergillus fumigatus allergen

GENE ACCESSION
(Af293)

Type allergens from other fungi

Related fungal allergens

Asp f1 

AFUA_5G02330

 

 

Asp f 2

AFUA_4G09580

 

 

Asp f  3

AFUA_6G02280

 

Cand b 2 (39); Pen c 3 (82); Can a 2 (40); Mala f 2 (44); Mala f 3 (46); Mala s 5  (?)(48); Mala s 1 (43)

Asp f  4

AFUA_2G03830

 

 

Asp f  6

AFUA_1G14550

 

Mala s 11 (52); Sac c MnSOD (53)

Asp f  5

AFUA_8G07080

 

 

Asp f  7

AFUA_4G06670

 

 

Asp f  8

AFUA_2G10100

 

Alt a 6 (82); Cla h 3 (80); Fus c 1 (81);

Asp f  9

AFUA_1G16190

 

 

Asp f  10

AFUA_5G13300

 

 

Asp f  11

AFUA_2G03720

 

Mala s 6 (62) (72 to AFUA_3g07430); Psi c 2 (61)

Asp f  12

AFUA_5G04170

 

Mal s 10 (36)

Asp f  13

AFUA_2G12630

 

Asp fl 13 (81) Pen c 13 fragment*; Tri t 4 fragment*

Asp f  17

AFUA_4G03240

 

 

Asp f  18

AFUA_5G09210

 

Asp n 18 (69); Pen n 18 (68); Pen n 13 (40); Pen o 18 (70); Pen c18 (72); Pen c2 (82); Pen c 1 (38); Tri r2 (40); Tri m 2 (46); Rho m 2 (52); Cla h 9

Asp f 22

AFUA_6G06770

 

Alt a 11 (prev 5)(87); Cla h 6 (83); Pen c 22 (90); Cand a enolase (73); Rho m 1 (75); Sac c Enolase (72)

Asp f  23

AFUA_2G11850

 

 

 

AFUA_1G12610 (52)

Mala s 10

 

 

AFUA_1G07440 (61)

Alt a 3

Cla h 4 (85); Pen c19 (90)

 

AFUA_1G06830 (80)

Alt a 12

Cla h 12 (71)

 

AFUA_4G11800 (44)

Asp o 13

Asp fl 1 (78)

 

AFUA_2G09030 (59)

Tri r 4

Tri sc 4 (57); Tri m 4 (57)

 

AFUA_6G11430 (67)

Alt a 10

Cla h 3 (71)

 

AFUA_5G06240 (59)

Can a 1

 

 

AFUA_4G00610 (40)

Mala s 12

 

 

AFUA_3G10460 (58)

Alt a NTF2

Cla h NTF2 (64)

 

AFUA_2G06150 (62)

Alt a 4

 

 

AFUA_1G02820 (69)

Alt a 7

Cla h 5 (61)

 

AFUA_3G11690 (75)

Candida 37KDa allergen

 

 

AFUA_1G16920 (63)

Asp n 14

 

 

AFUA_2G00690 (63)

Asp n glucoamylase

 

 

AFUA_4G10130 (78)

Asp o 21

 

 

AFUA_6G11330 (31)

Asp n 25

 

 

AFUA_5G09580 (28)

Cla h CH

 

 

AFUA_8G05020 (79)

Pen ch 20

 

 

AFUA_1G11190 (65)

Pen c 24

 

 

AFUA_6G11030 (39)

Cop c 3

 

 

AFUA_8G01090 (53

Cop c 2

Fus c 2 (53)

 

AFUA_4G09090 (52)

Fus c 2

Cop c 2 (53)

 

AFUA_1G09670 (42)

Fus c 3

 

 

AFUA_7G05740 (65)

Mala f 4

 

 

AFUA_6G09690 (94)

Alt a GST

 

 

AFUA_5G02040 (42)

Asp o lipase

 

Table 2 Comparative analysis of allergen orthologues in Aspergillus genomes:

Here the known and predicited allergens from A.fumigatus from Table 1 are used to find homologues in the other Aspergillus species. Only a few of these proteins are confirmed allergens (these are shown in red text). It is noticeable that not all Aspergillus species possess all of the allergen gene homologues

Allergen Gene Name

 

Af293

(A. fumigatus)

 

Af1163

(A. fumigatus)

N.fischeri A.clavatus A.terreus A.oryzae A.nidulans A.niger
Asp f 1   mitogillin ribotoxin AFUA_5G02330 AFUB_050860 NFIA_039760 ACLA_002920
Asp f 2  major allergen Asp F2 AFUA_4G09580 AFUB_066690 NFIA_106430 ACLA_048860 ATEG_00792 AO090005000939 AN1832.3
Asp f 3  peroxiredoxin AFUA_6G02280 AFUB_096050 NFIA_048550 ACLA_098190 ATEG_07222 AO090120000112 AN8692.3 An12g08570
Asp f 4  allergen Asp F4 AFUA_2G03830 AFUB_020900 NFIA_080630 ACLA_090690 ATEG_09507 AN3804.3
Asp f 5  elastinolytic metalloproteinase Mep AFUA_8G07080 AFUB_080720 NFIA_099860 ACLA_060300 ATEG_07544 AO090011000036 An01g02070
Asp f 6  Mn superoxide dismutase MnSOD AFUA_1G14550 AFUB_014080 NFIA_010880 ACLA_020890 ATEG_00657 AN0785.3 An01g12530
Asp f 7  allergen Asp F7 AFUA_4G06670 AFUB_063750 NFIA_109540 ACLA_045920 AN4379.3
Asp f 8  60S acidic ribosomal protein P2 AFUA_2G10100 AFUB_025910 NFIA_085510 ACLA_069130 ATEG_04444 AO090011000626 AN5996.3 An16g04930
Asp f 9  extracellular cell wall glucanase Crf1 AFUA_1G16190 AFUB_015530 NFIA_009250 ACLA_019370 ATEG_05185 AO090005001090 AN0933.3 An01g11010
Asp f 10  aspartic endopeptidase Pep1/aspergillopepsin F AFUA_5G13300 AFUB_061010 NFIA_073740 ACLA_016280 ATEG_06182 AO090120000474 AN6888.3 An14g04710
Asp f 11  peptidyl-prolyl cis-trans isomerase AFUA_2G03720 AFUB_020790 NFIA_080530 ACLA_090800 ATEG_09518 AO090120000215 AN3814.3 An07g08300
Asp f 12  molecular chaperone Mod-E/Hsp90/Hsp1 AFUA_5G04170 AFUB_052690 NFIA_037930 ACLA_000990 ATEG_07996 AO090102000620 AN8269.3 An09g06590
Asp f 13  allergenic cerato-platanin Asp F13 AFUA_2G12630 AFUB_028280 NFIA_087760 ACLA_071510 ATEG_01242 AO090026000357 AN6273.3 An02g01550
Asp f 17  cell wall galactomannoprotein Mp1 AFUA_4G03240 AFUB_099880 NFIA_030220 ACLA_055290 ATEG_04781 AO090011000119 An14g02100
Asp f 18  autophagic serine protease Alp2 AFUA_5G09210 AFUB_056750 NFIA_078120 ACLA_011360 ATEG_06546 AO090020000517 AN10030.3 An07g03880
Asp f 22  enolase/allergen Asp F 22 AFUA_6G06770 AFUB_072700 NFIA_052420 ACLA_088550 ATEG_02902 AO090003000055 AN5746.3 An18g06250
Asp f 23  60S ribosomal protein L3 AFUA_2G11850 AFUB_027590 NFIA_087080 ACLA_070790 ATEG_01126 AO090026000458 AN6202.3 An02g03950
Asp f 27  peptidyl-prolyl cis-trans isomerase/cyclophilin AFUA_3G07430 AFUB_041650 NFIA_069730 ACLA_035500 AO090120000486 AN8605.3
Asp f 28  thioredoxin AFUA_6G10300 AFUB_076350 NFIA_056080 ACLA_084040 ATEG_07928 AO090124000008 AN8571.3 An03g02980
Asp f 29  thioredoxin TrxA AFUA_5G11320 AFUB_058890 NFIA_075950 ACLA_014400 ATEG_07726 AO090026000708 AN0170.3 An01g02500
predicted thioredoxin AFUA_8G01090 AFUB_085510 NFIA_094530 AO090005001065 An18g03380
predicted beta-xylosidase XylA AFUA_1G16920 AFUB_016310 ACLA_018590 ATEG_05106 AO090005000986 AN2359.3 An01g09960
predicted alpha-amylase AFUA_4G10130 AFUB_067250 NFIA_105920 ACLA_049350 AO090120000196 AN2018.3 An12g06930
predicted alcohol dehydrogenase AFUA_5G06240 AFUB_053780 NFIA_036880 ACLA_009560 ATEG_09407 An17g01530
predicted glutathione S-transferase GliG AFUA_6G09690 AFUB_075740 NFIA_055380 ACLA_066850 AO090001000040
predicted molecular chaperone Hsp70 AFUA_1G07440 AFUB_007770 NFIA_017310 ACLA_027170 ATEG_10178 AO090012000995 AN5129.3
predicted 60S acidic ribosomal protein  P1 AFUA_1G06830 AFUB_007210 NFIA_017860 ACLA_027740 ATEG_02935 AO090001000485 AN5719.3 An18g05860
predicted glucan 1,4-alpha-glucosidase (glucoamylase) AFUA_2G00690 AFUB_017770 NFIA_032960 ACLA_094080 ATEG_04375 AO090010000746 AN7402.3 An03g06550
predicted RNA binding protein MSSP-2 AFUA_6G11030 AFUB_077060 NFIA_056760 ACLA_084710 ATEG_05061 AO090023000517 AN0592.3 An08g07820
predicted aryl-alcohol dehydrogenase AFUA_4G00610 AFUB_101160 NFIA_045070 ACLA_078430 ATEG_06402 AO090003001409 AN8329.3 An02g00400
predicted eukaryotic translation elongation factor 1 AFUA_1G11190 AFUB_010620 NFIA_014440 ACLA_024360 ATEG_00321 AO090038000287 AN1162.3 An08g03490
predicted alkaline serine protease Alp1 AFUA_4G11800 AFUB_068800 NFIA_104430 ACLA_050840 ATEG_03900 AO090003001036 AN5558.3 An09g03780
predicted protein disulfide isomerase Pdi1 AFUA_2G06150 AFUB_023230 NFIA_082940 ACLA_068160 ATEG_05609 AO090001000733 AN7436.3 An02g14800
predicted NADH-quinone oxidoreductase Pst2 AFUA_1G02820 AFUB_003200 NFIA_021810 ACLA_031610 ATEG_01946 AO090005000812 AN0297.3 An01g05340
predicted extracellular lipase, putative AFUA_5G02040 AFUB_050560 NFIA_040080 ACLA_003230 ATEG_09822 AO090001000143 AN8046.3 An09g02180
predicted beta-N-acetylhexosaminidase NagA AFUA_8G05020 AFUB_082480 NFIA_097830 ACLA_058420 ATEG_00123 AO090005000639 AN1502.3 An09g02240
predicted histidine acid phosphatase AFUA_6G11330 AFUB_077350 NFIA_057030 ACLA_085000 ATEG_05038 AO090023000481 AN0564.3 An09g00310
predicted thioredoxin AFUA_4G09090 AFUB_066190 NFIA_107080 ACLA_048460 ATEG_05305 AO090023000652 AN1639.3 An04g04040
predicted conidial hydrophobin Hyp1/RodA AFUA_5G09580 AFUB_057130 NFIA_077730 ACLA_010960 ATEG_06492 AO090020000588 AN8803.3 An07g03340
predicted secreted dipeptidyl peptidase DppV AFUA_2G09030 AFUB_024920 NFIA_084570 ACLA_080850 ATEG_09875 20235.m00900 AN2572.3 An12g04700
predicted Hsp70 chaperone Hsp88 AFUA_1G12610 AFUB_012080 NFIA_012940 ACLA_022850 ATEG_00453 AO090113000129 AN1047.3 An08g05300
predicted aldehyde dehydrogenase AldA AFUA_6G11430 AFUB_077440 NFIA_057120 ACLA_085090 ATEG_05020 AO090023000467 AN0554.3 An08g07290
predicted HLH transcription factor (GlcD gamma) AFUA_1G09670 AFUB_009120 NFIA_015940 ACLA_025830 ATEG_04204 AO090012000876 AN1298.3 An08g01380
predicted malate dehydrogenase, NAD-dependent AFUA_7G05740 AFUB_091320 NFIA_026980 ACLA_007430 ATEG_06358 AO090005000438 AN6717.3 An07g02160
predicted nuclear transport factor NTF-2 AFUA_3G10460 AFUB_038700 NFIA_066820 ACLA_038360 ATEG_04578 20219.m01412 AN4942.3 An16g04400