USTQ_ASPFN
ID USTQ_ASPFN Reviewed; 358 AA.
AC B8NM74;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Tyrosinase ustQ {ECO:0000303|PubMed:24841822};
DE EC=1.14.18.1 {ECO:0000305|PubMed:24841822};
DE AltName: Full=Ustiloxin B biosynthesis protein Q {ECO:0000303|PubMed:24841822};
GN Name=ustQ {ECO:0000303|PubMed:24841822}; ORFNames=AFLA_095060;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX PubMed=24841822; DOI=10.1016/j.fgb.2014.04.011;
RA Umemura M., Nagano N., Koike H., Kawano J., Ishii T., Miyamura Y.,
RA Kikuchi M., Tamano K., Yu J., Shin-ya K., Machida M.;
RT "Characterization of the biosynthetic gene cluster for the ribosomally
RT synthesized cyclic peptide ustiloxin B in Aspergillus flavus.";
RL Fungal Genet. Biol. 68:23-30(2014).
RN [3]
RP FUNCTION.
RX PubMed=27166860; DOI=10.1002/anie.201602611;
RA Ye Y., Minami A., Igarashi Y., Izumikawa M., Umemura M., Nagano N.,
RA Machida M., Kawahara T., Shin-Ya K., Gomi K., Oikawa H.;
RT "Unveiling the biosynthetic pathway of the ribosomally synthesized and
RT post-translationally modified peptide ustiloxin B in filamentous fungi.";
RL Angew. Chem. Int. Ed. 55:8072-8075(2016).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26703898; DOI=10.1016/j.fgb.2015.12.010;
RA Nagano N., Umemura M., Izumikawa M., Kawano J., Ishii T., Kikuchi M.,
RA Tomii K., Kumagai T., Yoshimi A., Machida M., Abe K., Shin-ya K., Asai K.;
RT "Class of cyclic ribosomal peptide synthetic genes in filamentous fungi.";
RL Fungal Genet. Biol. 86:58-70(2016).
CC -!- FUNCTION: Tyrosinase; part of the gene cluster that mediates the
CC biosynthesis of the secondary metabolite ustiloxin B, an antimitotic
CC tetrapeptide (PubMed:24841822, PubMed:27166860, PubMed:26703898).
CC First, ustA is processed by the subtilisin-like endoprotease Kex2 that
CC is outside the ustiloxin B gene cluster, at the C-terminal side of Arg-
CC Lys, after transfer to Golgi apparatus through the endoplasmic
CC reticulum (ER) (PubMed:24841822). Cleavage by KEX2 generates 16
CC peptides YAIG-I to YAIG-XVI (PubMed:24841822). To process the precursor
CC peptide further, at least two peptidases are necessary to cleave the N-
CC terminal and C-terminal sides of the Tyr-Ala-Ile-Gly core peptide which
CC serves as backbone for the synthesis of ustiloxin B, through
CC cyclization and modification of the tyrosine with a non-protein coding
CC amino acid, norvaline (PubMed:24841822). One of the two peptidases must
CC be the serine peptidase ustP; and the other pepdidase is probably ustH
CC (PubMed:24841822). Macrocyclization of the core peptide derived from
CC ustA requires the tyrosinase ustQ, as well as the homologous oxidases
CC ustYa and ustYb, and leads to the production of the first cyclization
CC product N-desmethylustiloxin F (PubMed:27166860, PubMed:26703898). For
CC the formation of N-desmethylustiloxin F, three oxidation steps are
CC required, hydroxylation at the benzylic position, hydroxylation at
CC either the aromatic ring of Tyr or beta-position of Ile, and oxidative
CC cyclization (PubMed:27166860). UstQ may catalyze the oxidation of a
CC phenol moiety, whereas the ustYa and ustYb are most likely responsible
CC for the remaining two-step oxidations (PubMed:27166860). N-
CC desmethylustiloxin F is then methylated by ustM to yield ustiloxin F
CC which in turn substrate of the cytochrome P450 monooxygenase ustC which
CC catalyzes the formation of S-deoxyustiloxin H (PubMed:27166860). The
CC flavoprotein monooxygenases ustF1 and ustF2 then participate in the
CC modification of the side chain of S-deoxyustiloxin H, leading to the
CC synthesis of an oxime intermediate, via ustiloxin H (PubMed:27166860).
CC Finally, carboxylative dehydration performed by the cysteine
CC desulfurase-like protein ustD yields ustiloxin B (PubMed:27166860).
CC {ECO:0000269|PubMed:24841822, ECO:0000269|PubMed:26703898,
CC ECO:0000269|PubMed:27166860}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone; Xref=Rhea:RHEA:34287,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57504,
CC ChEBI:CHEBI:57924; EC=1.14.18.1;
CC Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosine + O2 = H2O + L-dopaquinone; Xref=Rhea:RHEA:18117,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57924,
CC ChEBI:CHEBI:58315; EC=1.14.18.1;
CC Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:Q9ZP19};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:24841822}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Decreases the production of ustiloxin B
CC (PubMed:24841822, PubMed:26703898). {ECO:0000269|PubMed:24841822,
CC ECO:0000269|PubMed:26703898}.
CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
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DR EMBL; EQ963480; EED49425.1; -; Genomic_DNA.
DR RefSeq; XP_002381326.1; XM_002381285.1.
DR AlphaFoldDB; B8NM74; -.
DR SMR; B8NM74; -.
DR STRING; 5059.CADAFLAP00009191; -.
DR EnsemblFungi; EED49425; EED49425; AFLA_095060.
DR VEuPathDB; FungiDB:AFLA_095060; -.
DR eggNOG; ENOG502RM4B; Eukaryota.
DR HOGENOM; CLU_035914_1_2_1; -.
DR OMA; HRWTLHI; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004503; F:tyrosinase activity; IEA:UniProtKB-EC.
DR Gene3D; 1.10.1280.10; -; 1.
DR InterPro; IPR008922; Di-copper_centre_dom_sf.
DR InterPro; IPR002227; Tyrosinase_Cu-bd.
DR Pfam; PF00264; Tyrosinase; 1.
DR PRINTS; PR00092; TYROSINASE.
DR SUPFAM; SSF48056; SSF48056; 1.
DR PROSITE; PS00497; TYROSINASE_1; 1.
DR PROSITE; PS00498; TYROSINASE_2; 1.
PE 1: Evidence at protein level;
KW Copper; Glycoprotein; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..358
FT /note="Tyrosinase ustQ"
FT /id="PRO_0000437302"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 128
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 137
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 266
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 270
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 292
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 358 AA; 40248 MW; 350467FF930C9DF2 CRC64;
MAVEYFQEKL NKWRYSPVAG SPDEEGGNAT VKPKASFVPV YAGLTIISLI TVTVSLVHLL
SGTGTTTTFP PCKNPAVRRE WRSLTSSEKQ NFTQAVICLA SIPSTWQPNG TIYDDFAILH
GGIGSWCHRS ASFLPWHRYT LVVFEKALRE HCGFTGQVPY WDWTLDWMNL ANSSIFNSVD
GFGGDGDRTG QEVVGGGRCV IDGPFAGLQP ILYNHTYVRH CIARGFRDGD QAGRISGEYY
RPESIGGILR KQSYVELVRE VEIYLHNPLH QGVNGDFLAM TAANDPLFYV HHAQLDRLWW
RWQQESPDLR LKEYHGKHMY NSTGNATLDD ILMYGGFAED IPVSRVMDTK GGFLCYTY
