HIMC_ASPJA
ID HIMC_ASPJA Reviewed; 554 AA.
AC A0A2Z5TMB8;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Cytochrome P450 monooxygenase himC {ECO:0000303|PubMed:29314577};
DE EC=1.-.-.- {ECO:0000305|PubMed:29314577};
DE AltName: Full=Himeic acid A biosynthesis cluster protein C {ECO:0000303|PubMed:29314577};
GN Name=himC {ECO:0000303|PubMed:29314577};
OS Aspergillus japonicus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=34381;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=MF275;
RX PubMed=29314577; DOI=10.1002/cbic.201700584;
RA Hashimoto M., Kato H., Katsuki A., Tsukamoto S., Fujii I.;
RT "Identification of the biosynthetic gene cluster for himeic acid A: a
RT ubiquitin-activating enzyme (E1) inhibitor in Aspergillus japonicus
RT MF275.";
RL ChemBioChem 19:535-539(2018).
RN [2]
RP FUNCTION.
RX PubMed=29486950; DOI=10.1016/j.bmc.2018.02.034;
RA Katsuki A., Kato H., Tahara Y., Hashimoto M., Fujii I., Tsukamoto S.;
RT "pH-dependent production of himeic acid A and its non-enzymatic conversions
RT to himeic acids B and C.";
RL Bioorg. Med. Chem. 26:1869-1874(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the him gene cluster
CC that mediates the biosynthesis of himeic acid A, a ubiquitin-activating
CC enzyme (E1) inhibitor (PubMed:29314577). First, himA, together with the
CC trans-enoyl reductase himH, catalyzes the formation of apolyketide
CC chain, which is then condensed with leucine by the NRPS activity of
CC himA. Dieckmann cyclization and release from himA gives a tetramic acid
CC intermediate as the product of himA PKS-NRPS (PubMed:29314577). HimG
CC then catalyzes alpha-oxidation of the tetramic acid ring, with a
CC subsequent rearrangement to yield apyrone intermediate (Probable). Two
CC terminal methyl groups of polyketide and amide side chains are oxidized
CC to carboxylic acids by himC cytochrome P450 monooxygenase to form
CC himeic acid A (Probable). Himeic acid A is further converted to himeic
CC acid B and C during culture growth. No gene responsible for pyrone to
CC pyridone conversion was found in the him gene cluster and himeic acid A
CC is non-enzymatically converted to himeic acid C by the incorporation of
CC an ammonium nitrogen atom in a pH5 buffer, and to himeic acid B at a
CC conversion ratio of 50% during incubation in MeOH for 5 days
CC (PubMed:29486950). {ECO:0000269|PubMed:29314577,
CC ECO:0000269|PubMed:29486950, ECO:0000305|PubMed:29314577}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:29314577}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; LC331673; BBA91558.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2Z5TMB8; -.
DR SMR; A0A2Z5TMB8; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002974; Cyt_P450_E_CYP52.
DR InterPro; IPR002402; Cyt_P450_E_grp-II.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00464; EP450II.
DR PRINTS; PR01239; EP450IICYP52.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..554
FT /note="Cytochrome P450 monooxygenase himC"
FT /id="PRO_0000445944"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 501
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 554 AA; 62777 MW; C13DE37B1B1DFEE9 CRC64;
MEDIVNRLYA FDWRSLSLGS VPAPTPAPAP QSSVVHHLIA WWDQSKDSMQ QYSVASVAIA
GFTALVVSVA LYRALFSQRQ RHDPLNQGCQ PLRMYPHKDR IFGLDFVYQN VTTFRRHKYL
ETLKNRYQTL GTTYGVRVFN RRGILTSDPE NIKTILSTRF KDYSLGNRVP IMGPLLGRGI
FVSDGQDWSH SRALLRPNFV KEQVADLQMI ETHLAQLLKL IPSDGRTVVE LQDLFLRFTL
DSATDFLFGH SLHTLSRGTA KDQQFGQAFA LALDDIALQF RLGPWRALRR PNKDALAAYE
ICRGYVEGFV ADAMAYRHGK ASSTGDKNTS DRSYFLKELA QATDDRDRIR DELLNILIAG
RDTTASLLGS LFYVLARHPE VWQKLRSEAA TQLQGAAPNY EQLRNLQYTR HCINETLRLY
PPVPNNTKMA VCDTILPRGG GPKGDAPVFV PKGCTMIYTV YAMHRRTDLF GPDAEEFRPE
RWATQRFSWE FLPFNGGPRI CLGQQYALTE AMYVLVRFAQ TFQTIEAQDP APWTEQLTLT
LASNNGVKVR LKGA
