ABR2_ASPFU
ID ABR2_ASPFU Reviewed; 587 AA.
AC E9RBR0;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Laccase abr2 {ECO:0000303|PubMed:10515939};
DE EC=1.10.3.- {ECO:0000305|PubMed:16988817};
DE AltName: Full=Conidial pigment biosynthesis oxidase abr2 {ECO:0000305};
DE Flags: Precursor;
GN Name=abr2 {ECO:0000303|PubMed:10515939}; ORFNames=AFUA_2G17530;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION.
RX PubMed=10515939; DOI=10.1128/jb.181.20.6469-6477.1999;
RA Tsai H.F., Wheeler M.H., Chang Y.C., Kwon-Chung K.J.;
RT "A developmentally regulated gene cluster involved in conidial pigment
RT biosynthesis in Aspergillus fumigatus.";
RL J. Bacteriol. 181:6469-6477(1999).
RN [3]
RP FUNCTION.
RX PubMed=14970241; DOI=10.1099/jmm.0.05421-0;
RA Youngchim S., Morris-Jones R., Hay R.J., Hamilton A.J.;
RT "Production of melanin by Aspergillus fumigatus.";
RL J. Med. Microbiol. 53:175-181(2004).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=16988817; DOI=10.1007/s00203-006-0144-2;
RA Sugareva V., Haertl A., Brock M., Huebner K., Rohde M., Heinekamp T.,
RA Brakhage A.A.;
RT "Characterisation of the laccase-encoding gene abr2 of the
RT dihydroxynaphthalene-like melanin gene cluster of Aspergillus fumigatus.";
RL Arch. Microbiol. 186:345-355(2006).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLN-217.
RX PubMed=19703288; DOI=10.1186/1471-2180-9-177;
RA Pihet M., Vandeputte P., Tronchin G., Renier G., Saulnier P.,
RA Georgeault S., Mallet R., Chabasse D., Symoens F., Bouchara J.P.;
RT "Melanin is an essential component for the integrity of the cell wall of
RT Aspergillus fumigatus conidia.";
RL BMC Microbiol. 9:177-177(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19156203; DOI=10.1371/journal.pone.0004224;
RA Jackson J.C., Higgins L.A., Lin X.;
RT "Conidiation color mutants of Aspergillus fumigatus are highly pathogenic
RT to the heterologous insect host Galleria mellonella.";
RL PLoS ONE 4:E4224-E4224(2009).
RN [7]
RP FUNCTION.
RX PubMed=20145078; DOI=10.1128/aac.01504-09;
RA Ben-Ami R., Lewis R.E., Leventakos K., Latge J.P., Kontoyiannis D.P.;
RT "Cutaneous model of invasive aspergillosis.";
RL Antimicrob. Agents Chemother. 54:1848-1854(2010).
RN [8]
RP FUNCTION.
RX PubMed=21747802; DOI=10.3389/fmicb.2011.00096;
RA Thywissen A., Heinekamp T., Dahse H.M., Schmaler-Ripcke J., Nietzsche S.,
RA Zipfel P.F., Brakhage A.A.;
RT "Conidial dihydroxynaphthalene melanin of the human pathogenic fungus
RT Aspergillus fumigatus interferes with the host endocytosis pathway.";
RL Front. Microbiol. 2:96-96(2011).
RN [9]
RP FUNCTION.
RX PubMed=21573171; DOI=10.1371/journal.pone.0019591;
RA Mech F., Thywissen A., Guthke R., Brakhage A.A., Figge M.T.;
RT "Automated image analysis of the host-pathogen interaction between
RT phagocytes and Aspergillus fumigatus.";
RL PLoS ONE 6:E19591-E19591(2011).
RN [10]
RP INDUCTION.
RX PubMed=24123270; DOI=10.1128/ec.00217-13;
RA Upadhyay S., Torres G., Lin X.;
RT "Laccases involved in 1,8-dihydroxynaphthalene melanin biosynthesis in
RT Aspergillus fumigatus are regulated by developmental factors and copper
RT homeostasis.";
RL Eukaryot. Cell 12:1641-1652(2013).
RN [11]
RP FUNCTION.
RX PubMed=24818666; DOI=10.1128/iai.01726-14;
RA Bayry J., Beaussart A., Dufrene Y.F., Sharma M., Bansal K., Kniemeyer O.,
RA Aimanianda V., Brakhage A.A., Kaveri S.V., Kwon-Chung K.J., Latge J.P.,
RA Beauvais A.;
RT "Surface structure characterization of Aspergillus fumigatus conidia
RT mutated in the melanin synthesis pathway and their human cellular immune
RT response.";
RL Infect. Immun. 82:3141-3153(2014).
RN [12]
RP FUNCTION.
RX PubMed=25684622; DOI=10.1111/1462-2920.12808;
RA Hillmann F., Novohradska S., Mattern D.J., Forberger T., Heinekamp T.,
RA Westermann M., Winckler T., Brakhage A.A.;
RT "Virulence determinants of the human pathogenic fungus Aspergillus
RT fumigatus protect against soil amoeba predation.";
RL Environ. Microbiol. 17:2858-2869(2015).
RN [13]
RP SUBCELLULAR LOCATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26972005; DOI=10.1016/j.celrep.2016.02.059;
RA Upadhyay S., Xu X., Lowry D., Jackson J.C., Roberson R.W., Lin X.;
RT "Subcellular compartmentalization and trafficking of the biosynthetic
RT machinery for fungal melanin.";
RL Cell Rep. 14:2511-2518(2016).
CC -!- FUNCTION: Laccase; part of the gene cluster that mediates the
CC biosynthesis of dihydroxynaphthalene (DHN)-melanin, a bluish-green
CC pigment and a structural component of the conidial wall
CC (PubMed:10515939, PubMed:14970241, PubMed:19156203). The first step of
CC the pathway is the production of the heptaketide naphtopyrone YWA1 by
CC the polyketide synthase alb1 though condensation of acetyl-CoA with
CC malonyl-CoA (PubMed:10515939). The naphtopyrone YWA1 is then converted
CC to the pentaketide 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) by the
CC heptaketide hydrolyase ayg1 though chain-length shortening
CC (PubMed:10515939). 1,3,6,8-THN is substrate of the hydroxynaphthalene
CC reductase arp2 to yield scytalone (PubMed:10515939). The scytalone
CC dehydratase arp1 then reduces scytalone to 1,3,8-THN (PubMed:10515939).
CC 1,3,8-THN is also substrate of the hydroxynaphthalene reductase arp2 to
CC yield vermelone (PubMed:10515939). Vermelone is further converted by
CC the multicopper oxidase abr1 to 1,8-DHN (PubMed:10515939). Finally the
CC laccase abr2 transforms 1,8-DHN to DHN-melanin (PubMed:10515939). DHN-
CC melanin biosynthesis appears to be initiated in endosomes where early
CC enzymes (abl1, ayg1, arp1 and arp2) localize, with exocytosis leading
CC to melanin deposition on the cell surface where late enzymes (abr1 and
CC abr2) localize (PubMed:26972005). DHN-melanin is an important
CC structural component of the outer cell wall and is required for the
CC presence of conidial surface hydrophobins (PubMed:19703288). DHN-
CC melanin also plays a crucial role in fungal virulence, including a
CC protective role against the host's immune defenses (PubMed:19156203,
CC PubMed:20145078, PubMed:21747802, PubMed:21573171, PubMed:24818666).
CC DHN-melanin protects also conidia against amoeba predation
CC (PubMed:25684622). {ECO:0000269|PubMed:10515939,
CC ECO:0000269|PubMed:19156203, ECO:0000269|PubMed:19703288,
CC ECO:0000269|PubMed:20145078, ECO:0000269|PubMed:21573171,
CC ECO:0000269|PubMed:21747802, ECO:0000269|PubMed:24818666,
CC ECO:0000269|PubMed:25684622, ECO:0000269|PubMed:26972005}.
CC -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis.
CC {ECO:0000269|PubMed:10515939, ECO:0000269|PubMed:19156203}.
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:26972005}.
CC -!- INDUCTION: Expression is up-regulated upon hyphal competency and
CC drastically increased during conidiation (PubMed:16988817,
CC PubMed:24123270). Expression is controlled by brlA, the master
CC regulator of conidiophore development, and is responsive to the copper
CC level in the medium (PubMed:24123270). {ECO:0000269|PubMed:24123270}.
CC -!- DISRUPTION PHENOTYPE: Changes the gray-green conidial pigment to a
CC brown color and reduces the ornamentation of conidia (PubMed:16988817,
CC PubMed:26972005). Reduces overall laccase activity only during
CC sporulation, but not during vegetative growth (PubMed:16988817). Causes
CC enhanced insect mortality compared to the parent strain in a wax moth
CC Galleria mellonella infection model, probably through exacerbated
CC immune response of the wax moth (PubMed:19156203).
CC {ECO:0000269|PubMed:16988817, ECO:0000269|PubMed:19156203,
CC ECO:0000269|PubMed:26972005}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94050.2; -; Genomic_DNA.
DR RefSeq; XP_756088.2; XM_750995.2.
DR AlphaFoldDB; E9RBR0; -.
DR SMR; E9RBR0; -.
DR STRING; 746128.CADAFUBP00003256; -.
DR EnsemblFungi; EAL94050; EAL94050; AFUA_2G17530.
DR GeneID; 3512772; -.
DR KEGG; afm:AFUA_2G17530; -.
DR VEuPathDB; FungiDB:Afu2g17530; -.
DR eggNOG; KOG1263; Eukaryota.
DR HOGENOM; CLU_006504_5_0_1; -.
DR InParanoid; E9RBR0; -.
DR OMA; WNYSSVE; -.
DR OrthoDB; 454773at2759; -.
DR UniPathway; UPA00785; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0052716; F:hydroquinone:oxygen oxidoreductase activity; IMP:AspGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042438; P:melanin biosynthetic process; IMP:AspGD.
DR GO; GO:0046148; P:pigment biosynthetic process; IMP:AspGD.
DR Gene3D; 2.60.40.420; -; 3.
DR InterPro; IPR001117; Cu-oxidase.
DR InterPro; IPR011706; Cu-oxidase_C.
DR InterPro; IPR045087; Cu-oxidase_fam.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR InterPro; IPR008972; Cupredoxin.
DR PANTHER; PTHR11709; PTHR11709; 1.
DR Pfam; PF00394; Cu-oxidase; 1.
DR Pfam; PF07731; Cu-oxidase_2; 1.
DR Pfam; PF07732; Cu-oxidase_3; 1.
DR SUPFAM; SSF49503; SSF49503; 3.
DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 1.
DR PROSITE; PS00080; MULTICOPPER_OXIDASE2; 1.
PE 1: Evidence at protein level;
KW Copper; Glycoprotein; Metal-binding; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..587
FT /note="Laccase abr2"
FT /id="PRO_5003243370"
FT DOMAIN 41..137
FT /note="Plastocyanin-like 1"
FT /evidence="ECO:0000255"
FT DOMAIN 168..350
FT /note="Plastocyanin-like 2"
FT /evidence="ECO:0000255"
FT DOMAIN 397..577
FT /note="Plastocyanin-like 3"
FT /evidence="ECO:0000255"
FT BINDING 75
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 77
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 119
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 121
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 487
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 462
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 504
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 217
FT /note="Q->E: Results in white conidial phenotype."
FT /evidence="ECO:0000269|PubMed:19703288"
SQ SEQUENCE 587 AA; 65289 MW; 73020B5AE34FE6D2 CRC64;
MWYQSASLLG VAAVAQAATV HYSLDLTWET GSPNGVSREM IFVNGQFPGP AIILNEGDEA
IIDVTNHLPF NTSIHFHGIE QKNTPWADGV VGLSQWAIQP GQSYTYQWRA DTYGTYWYHA
HDKAEIMDGL YGPVHIRPRP NRDSPFSMIS DDPADIRAMK QAERNGKLVM LSDWDHLTGQ
EYMKAMEETG YDIFCSDSVL INGRGSVFCH DPEELTQMVP PPELAILNSS LTDKGCLPFV
PPIQGNWEHH PDKVPPGLNE GCHPSTTQET IFTVDAAHQW ASFHFISAAS LKVLVVSIDE
HPMYVYEVDG RYIEPQLAHS VKLYNGERYS VMVKLDKEPA NYKMRAANDG GNQIVSGFAT
VTYEGGETSQ RPSQPYIDYG SRNTSADVIP LDTNHLPPYP AISPASEPDD FHILMLGRTN
SSWEWSLDGA AFLPSNLAAL PPAILSPQAP EFADALKITT RNDTWVDIVF QLVVSETTPI
QPPHPLHKHS NKGFLLGTGH GKFNWTSIKE AKEASPESFL ETPVYRDTFT TSPQGETWTA
IRYHVENPGP FLLHCHMTTH LQSGMGLILM DGVDVWPEVY ADMITPM
