Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

5'-hydroxyaverantin dehydrogenase

Gene

aflH

Organism
Aspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

5'-hydroxyaverantin dehydrogenase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:15006741). The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741). The first step of the pathway is the conversion of acetate to norsolorinic acid (NOR) and requires the fatty acid synthase subunits aflA and aflB, as well as the PKS aflC (PubMed:15006741). AflC combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor NOR (PubMed:18403714). The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase aflA/aflB (PubMed:16256699). The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin (PubMed:10584035). The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN (PubMed:15006741). The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN) (PubMed:8368836). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway (PubMed:14602595, PubMed:15006741, PubMed:11055914, PubMed:15932995). The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA) (PubMed:15006741). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL) (PubMed:15006741). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen (PubMed:15006741, PubMed:8368837, PubMed:15932995). Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA) (PubMed:15006741, PubMed:8368837). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2 (PubMed:15006741). Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST) (PubMed:15006741, PubMed:1339261, PubMed:15771506). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring (PubMed:16332900, PubMed:16461654). The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST) (PubMed:10543813). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively (PubMed:8434913). Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytodhrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741, PubMed:11996570, PubMed:15528514, PubMed:18486503).1 Publication17 Publications

Catalytic activityi

(1'S,5'S)-hydroxyaverantin + NAD+ = 5'-oxoaverantin + NADH.1 Publication
(1'S,5'R)-hydroxyaverantin + NAD+ = 5'-oxoaverantin + NADH.1 Publication

Pathwayi: aflatoxin biosynthesis

This protein is involved in the pathway aflatoxin biosynthesis, which is part of Mycotoxin biosynthesis.1 Publication
View all proteins of this organism that are known to be involved in the pathway aflatoxin biosynthesis and in Mycotoxin biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei187Proton acceptorPROSITE-ProRule annotation1
Binding sitei191NADPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi20 – 48NADPBy similarityAdd BLAST29

GO - Molecular functioni

  • oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • aflatoxin biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-14032.
BRENDAi1.1.1.352. 523.
UniPathwayiUPA00287.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-hydroxyaverantin dehydrogenase1 Publication (EC:1.1.1.3521 Publication)
Short name:
HAVN dehydrogenase1 Publication
Alternative name(s):
Aflatoxin biosynthesis protein H1 Publication
Gene namesi
Name:aflH1 Publication
Synonyms:adhA1 Publication
ORF Names:P875_00052989-1
OrganismiAspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1)
Taxonomic identifieri1403190 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaeAspergillus
Proteomesi
  • UP000033540 Componenti: Unassembled WGS sequence

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Cells accumulate 5'-hydroxyaverantin.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004241621 – 2785'-hydroxyaverantin dehydrogenaseAdd BLAST278

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1

Keywords - PTMi

Acetylation

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Structurei

3D structure databases

ProteinModelPortaliP87017.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

KOiK17652.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 1 hit.
PfamiPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSiPR00081. GDHRDH.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P87017-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVLDTTVDL GTLQGKSALI TGGASGIGLA TARAWAAAGM YVTIADIQPL
60 70 80 90 100
ETGQNILADL AGGHVHYVCC DVTSWESQIT AFKEAIQFTP SKALDIVAAF
110 120 130 140 150
AGVSFAGGNQ VDHVLAAGDP RLDVNPSPPD IRNIQVNLIG VYYTSWLGLY
160 170 180 190 200
YLRLSPTNKA ANPSPDKSLI LMGSIGSYMD SPKASTYPAS KFGVRGLFRS
210 220 230 240 250
TRARTRELGV RCNLLAPWFI DTPLIAPMKK AMAARGIDMA QRLTFASVDA
260 270
CVEAATTCAA NPQLHGTPPI RYAYCLKT
Length:278
Mass (Da):29,557
Last modified:May 1, 2000 - v2
Checksum:i8C60C5437EB9BB71
GO

Sequence cautioni

The sequence KJK60750 differs from that shown. Reason: Erroneous gene model prediction. The predicted gene P875_00052989 has been split into 2 genes: P875_00052996-1 (aflH) and P875_00052996-2 (aflJ).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76621 Genomic DNA. Translation: AAB51228.3.
AY371490 Genomic DNA. Translation: AAS66009.1.
JZEE01000729 Genomic DNA. Translation: KJK60750.1. Sequence problems.

Genome annotation databases

KEGGiag:AAB51228.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76621 Genomic DNA. Translation: AAB51228.3.
AY371490 Genomic DNA. Translation: AAS66009.1.
JZEE01000729 Genomic DNA. Translation: KJK60750.1. Sequence problems.

3D structure databases

ProteinModelPortaliP87017.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

KEGGiag:AAB51228.

Phylogenomic databases

KOiK17652.

Enzyme and pathway databases

UniPathwayiUPA00287.
BioCyciMetaCyc:MONOMER-14032.
BRENDAi1.1.1.352. 523.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 1 hit.
PfamiPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSiPR00081. GDHRDH.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAFLH_ASPPU
AccessioniPrimary (citable) accession number: P87017
Secondary accession number(s): A0A0F0HZ42
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 16, 2013
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 77 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.