PYTH_ASPTN
ID PYTH_ASPTN Reviewed; 423 AA.
AC Q0CZG7;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Aspartic protease-like protein pytH {ECO:0000303|PubMed:32077283};
DE EC=3.4.23.- {ECO:0000305|PubMed:32077283};
DE AltName: Full=Pyranterreones biosynthesis cluster protein H {ECO:0000303|PubMed:32077283};
DE Flags: Precursor;
GN Name=pytH {ECO:0000303|PubMed:32077283}; ORFNames=ATEG_00917;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INDUCTION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=32077283; DOI=10.1021/acs.jnatprod.9b01140;
RA Tang S., Zhang W., Li Z., Li H., Geng C., Huang X., Lu X.;
RT "Discovery and characterization of a PKS-NRPS hybrid in Aspergillus terreus
RT by genome mining.";
RL J. Nat. Prod. 83:473-480(2020).
CC -!- FUNCTION: Aspartic protease-like protein; part of the gene cluster that
CC mediates the biosynthesis of pyranterreones, a family of antioxidative
CC compounds (PubMed:32077283). The first step of pyranonigrins
CC biosynthesis is performed by the hybrid PKS-NRPS synthetase pytA that
CC condenses 4 malonyl-CoA units ato the acetyl starter unit by the
CC modular PKS of pytA (PubMed:32077283). The acyl chain is then connected
CC to an L-serine through the amide bond by the modular NRPS of pytA
CC (PubMed:32077283). A tetramic acid is formed and released from the PKS-
CC NRPS pytA to give pyranterreone 5 with the help of the thioesterase
CC pytI (PubMed:32077283). Pyranterreone 5 could be methylated by pytC to
CC afford pyranterreone 6 (Probable). Both pyranterreones 5 and 6 are
CC subsequently oxidized by the FAD-linked oxidoreductase pytB and the
CC cytochrome P450 monooxygenase pytD to form the fused gamma-pyrone core,
CC resulting in pyranterreones 7 and 11, respectively (PubMed:32077283).
CC The hydroxy group at C-8 of pyranterreones 7 and 11 are dehydrated by
CC the aspartyl protease pytH to form a delta-7 double bond to give
CC pyranterreones 3 and 1, 2 accordingly (PubMed:32077283). The exo-
CC methylene of pyranterreone 3 could be reduced into a pendant methyl by
CC reductase pytE to provide pyranterreone 4, also known as cordylactam
CC (Probable). Pyranterreone 4 can be reconverted to pyranterreone 3
CC through pytB-catalyzed dehydrogenation or further oxidized to
CC pyranterreones 9 and 10 (Probable). {ECO:0000269|PubMed:32077283,
CC ECO:0000305|PubMed:32077283}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:32077283}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor pytR. {ECO:0000269|PubMed:32077283}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of most pyranterreones,
CC but accumulates pyranterreones 7 and 8. {ECO:0000269|PubMed:32077283}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CH476594; EAU39563.1; -; Genomic_DNA.
DR RefSeq; XP_001211003.1; XM_001211003.1.
DR AlphaFoldDB; Q0CZG7; -.
DR SMR; Q0CZG7; -.
DR EnsemblFungi; EAU39563; EAU39563; ATEG_00917.
DR GeneID; 4355680; -.
DR VEuPathDB; FungiDB:ATEG_00917; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_039077_0_0_1; -.
DR OMA; FVDWTWI; -.
DR OrthoDB; 550800at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd05471; pepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR034164; Pepsin-like_dom.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF00026; Asp; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 2: Evidence at transcript level;
KW Aspartyl protease; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW Reference proteome; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..423
FT /note="Aspartic protease-like protein pytH"
FT /id="PRO_5004170777"
FT DOMAIN 38..416
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 56
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 338..377
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
SQ SEQUENCE 423 AA; 47310 MW; B44AA2F7FF3B2CAC CRC64;
MWLSVALLTL LDGALAAPAR QHSGAFDMPL TWTPFGFTTD AIQIGTPPQP LVCFVDWTWI
GQYAFTPRCH GGSQGTYACL QHGQPLYNET ESRTFANQSV LYPERTWNPN HFFFYNDLSV
GFGSDIERVG PDHQARVTLQ LADMHFQLDM VYPFGGVYGL SPVFKSDNAS TQSPFYQMWQ
QGVYRSPLVS FVYCHNSTFD QPTPRRELCH GKDGLQTLGG PSPVLSLSDK NNSSPILWYD
NIVFPPVNEI EFVYQPAVYN YWALRLTRHL IGDEEQALNT SIGGNPGAIF DHASYGRGVP
MSENSYRRLI EITGGRPVVL DANVAPNNGN QSFVSVDCEK VSSFPNVKYV FEGHDRVWEV
TPANYVERRE VDGKEVCVLN VRTLGEGDWI IGNFGETFAK DKVVLFDFDK LRVGLADVPA
AAY
