ARP2_ASPFU
ID ARP2_ASPFU Reviewed; 273 AA.
AC E9QUT3;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Hydroxynaphthalene reductase arp2 {ECO:0000303|PubMed:19703288};
DE EC=1.1.-.- {ECO:0000305|PubMed:19703288};
DE AltName: Full=Conidial pigment biosynthesis oxidase arp2 {ECO:0000305};
GN Name=arp2 {ECO:0000303|PubMed:10515939}; ORFNames=AFUA_2G17560;
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, AND DISRUPTION PHENOTYPE.
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, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
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 [4]
RP FUNCTION.
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 [5]
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 [6]
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 [7]
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 [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [9]
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 [10]
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: Hydroxynaphthalene reductase; part of the gene cluster that
CC mediates the biosynthesis of dihydroxynaphthalene (DHN)-melanin, a
CC bluish-green pigment and a structural component of the conidial wall
CC (PubMed:10515939, PubMed:19156203). The first step of the pathway is
CC the production of the heptaketide naphtopyrone YWA1 by the polyketide
CC synthase alb1 though condensation of acetyl-CoA with malonyl-CoA
CC (PubMed:10515939). The naphtopyrone YWA1 is then converted to the
CC 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 -!- ACTIVITY REGULATION: Tricyclazole and pyroquilon inhibit arp2
CC hydroxynaphtalene reductase activity (PubMed:19703288).
CC {ECO:0000269|PubMed:19703288}.
CC -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis.
CC {ECO:0000269|PubMed:10515939, ECO:0000269|PubMed:19156203,
CC ECO:0000269|PubMed:19703288}.
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000269|PubMed:26972005}.
CC -!- DISRUPTION PHENOTYPE: Results in brownish conidial phenotype
CC (PubMed:19703288, PubMed:26972005). Results in an altered conidial
CC surface with masked surface rodlet layer, leaky cell wall allowing the
CC deposition of proteins on the cell surface and exposing the otherwise-
CC masked cell wall polysaccharides at the surface (PubMed:24818666).
CC {ECO:0000269|PubMed:19703288, ECO:0000269|PubMed:24818666,
CC ECO:0000269|PubMed:26972005}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94053.1; -; Genomic_DNA.
DR RefSeq; XP_756091.1; XM_750998.1.
DR AlphaFoldDB; E9QUT3; -.
DR SMR; E9QUT3; -.
DR STRING; 746128.CADAFUBP00003259; -.
DR SwissPalm; E9QUT3; -.
DR EnsemblFungi; EAL94053; EAL94053; AFUA_2G17560.
DR GeneID; 3513287; -.
DR KEGG; afm:AFUA_2G17560; -.
DR VEuPathDB; FungiDB:Afu2g17560; -.
DR eggNOG; KOG0725; Eukaryota.
DR HOGENOM; CLU_010194_1_3_1; -.
DR InParanoid; E9QUT3; -.
DR OMA; KHMVDAG; -.
DR OrthoDB; 913128at2759; -.
DR UniPathway; UPA00785; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0047039; F:tetrahydroxynaphthalene reductase activity; IMP:AspGD.
DR GO; GO:0042438; P:melanin biosynthetic process; IMP:AspGD.
DR GO; GO:0046148; P:pigment biosynthetic process; IMP:AspGD.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 3: Inferred from homology;
KW Endosome; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..273
FT /note="Hydroxynaphthalene reductase arp2"
FT /id="PRO_0000436876"
FT ACT_SITE 160
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 17..46
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
FT BINDING 70
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
FT BINDING 164
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
SQ SEQUENCE 273 AA; 28843 MW; B5F610612AFA41ED CRC64;
MVNTCTYLPL SGKVALVTGG GRGIGAGIAL ELARRGASVA INYGHSAKSA QEVVEAIQAI
GRQAVAIQAD LTCVPNIESL IQEVVRHFGR LDIVVSNSGM EKFKPLEETT LEDFNEVFNL
NTRAQMFVAR YAYDHIQPGG RVILMSSIAA GLGVPGHALY AGSKAAIEGF TRCLAADFGR
KGCTVNAIAP AGVKSDMWRE NAWRYAPGCD KSSSLEEIET ALASGSPLKR CGVPEDIGKV
VSFLASPDAE WVNGEFFSPP PCKGPLPGGD LEC
