SIDH_ASPFU
ID SIDH_ASPFU Reviewed; 270 AA.
AC Q4WF54;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 85.
DE RecName: Full=Mevalonyl-coenzyme A hydratase sidH {ECO:0000303|PubMed:22106303};
DE EC=4.2.1.- {ECO:0000305|PubMed:22106303};
DE AltName: Full=Siderophore biosynthesis protein H {ECO:0000303|PubMed:22106303};
GN Name=sidH {ECO:0000303|PubMed:22106303}; ORFNames=AFUA_3G03410;
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.
RX PubMed=15504822; DOI=10.1084/jem.20041242;
RA Schrettl M., Bignell E., Kragl C., Joechl C., Rogers T., Arst H.N. Jr.,
RA Haynes K., Haas H.;
RT "Siderophore biosynthesis but not reductive iron assimilation is essential
RT for Aspergillus fumigatus virulence.";
RL J. Exp. Med. 200:1213-1219(2004).
RN [3]
RP FUNCTION.
RX PubMed=16113265; DOI=10.1128/iai.73.9.5493-5503.2005;
RA Hissen A.H., Wan A.N., Warwas M.L., Pinto L.J., Moore M.M.;
RT "The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-
RT ornithine N(5)-oxygenase, is required for virulence.";
RL Infect. Immun. 73:5493-5503(2005).
RN [4]
RP FUNCTION.
RX PubMed=17845073; DOI=10.1371/journal.ppat.0030128;
RA Schrettl M., Bignell E., Kragl C., Sabiha Y., Loss O., Eisendle M.,
RA Wallner A., Arst H.N. Jr., Haynes K., Haas H.;
RT "Distinct roles for intra- and extracellular siderophores during
RT Aspergillus fumigatus infection.";
RL PLoS Pathog. 3:1195-1207(2007).
RN [5]
RP INDUCTION.
RX PubMed=18721228; DOI=10.1111/j.1365-2958.2008.06376.x;
RA Schrettl M., Kim H.S., Eisendle M., Kragl C., Nierman W.C., Heinekamp T.,
RA Werner E.R., Jacobsen I., Illmer P., Yi H., Brakhage A.A., Haas H.;
RT "SreA-mediated iron regulation in Aspergillus fumigatus.";
RL Mol. Microbiol. 70:27-43(2008).
RN [6]
RP FUNCTION.
RX PubMed=21622789; DOI=10.1128/aem.00182-11;
RA Blatzer M., Schrettl M., Sarg B., Lindner H.H., Pfaller K., Haas H.;
RT "SidL, an Aspergillus fumigatus transacetylase involved in biosynthesis of
RT the siderophores ferricrocin and hydroxyferricrocin.";
RL Appl. Environ. Microbiol. 77:4959-4966(2011).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22106303; DOI=10.1073/pnas.1106399108;
RA Yasmin S., Alcazar-Fuoli L., Gruendlinger M., Puempel T., Cairns T.,
RA Blatzer M., Lopez J.F., Grimalt J.O., Bignell E., Haas H.;
RT "Mevalonate governs interdependency of ergosterol and siderophore
RT biosyntheses in the fungal pathogen Aspergillus fumigatus.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E497-E504(2012).
RN [8]
RP SUBCELLULAR LOCATION, PEROXISOMAL TARGETING SIGNAL, AND FUNCTION.
RX PubMed=23617799; DOI=10.1111/mmi.12225;
RA Gruendlinger M., Yasmin S., Lechner B.E., Geley S., Schrettl M., Hynes M.,
RA Haas H.;
RT "Fungal siderophore biosynthesis is partially localized in peroxisomes.";
RL Mol. Microbiol. 88:862-875(2013).
CC -!- FUNCTION: Mevalonyl-coenzyme A hydratase; part of the siderophore
CC biosynthetic pathway (PubMed:22106303). Aspergillus fumigatus produces
CC 4 types of siderophores, low-molecular-mass iron chelators, including
CC excreted fusarinine C (FsC) and triacetylfusarinine C (TAFC) for iron
CC uptake and intacellular ferricrocin (FC) for hyphal and
CC hydroxyferricrocin (HFC) for conidial iron distribution and storage.
CC TAFC consists of 3 N(2)-acetyl-N(5)-anhydromevalonyl-N(5)-
CC hydroxyornithine residues cyclically linked by ester bonds; FC is a
CC cyclic hexapeptide with the structure Gly-Ser-Gly-(N(5)-acetyl-N(5)-
CC hydroxyornithine)x3. The biosynthesis of all four siderophores depends
CC on the hydroxylation of ornithine, catalyzed by the monooxygenase sidA
CC (PubMed:15504822, PubMed:16113265). Subsequently, the pathways for
CC biosynthesis of extra- and intracellular siderophores split
CC (PubMed:17845073). For biosynthesis of extracellular siderophores, the
CC transacylase sidF transfers anhydromevalonyl to N(5)-hydroxyornithine
CC (PubMed:17845073). The required anhydromevalonyl-CoA moiety is derived
CC from mevalonate by CoA ligation and dehydration catalyzed by sidI and
CC sidH respectively (PubMed:22106303). The acetylation of N(5)-
CC hydroxyornithine for FC biosynthesis involves the constitutively
CC expressed sidL (PubMed:21622789). FC is hydroxylated to HFC by an as
CC yet uncharacterized enzyme during conidiation (PubMed:17845073).
CC Assembly of fusarinine C (FsC) and FC is catalyzed by two different
CC nonribosomal peptide synthetases (NRPS), sidD and sidC respectively
CC (PubMed:17845073). Subsequently, sidG catalyzes N2-acetylation of FsC
CC for forming TAFC (PubMed:17845073). Both extra- and intracellular
CC siderophores are crucial for growth during iron limitation and
CC virulence (PubMed:16113265). {ECO:0000269|PubMed:15504822,
CC ECO:0000269|PubMed:16113265, ECO:0000269|PubMed:17845073,
CC ECO:0000269|PubMed:21622789, ECO:0000269|PubMed:22106303}.
CC -!- PATHWAY: Siderophore biosynthesis. {ECO:0000269|PubMed:22106303}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:23617799}.
CC Note=Targeted to peroxisomes via its PTS1-type peroxisomal targeting
CC signal and the corresponding receptor pexE (PubMed:23617799).
CC {ECO:0000269|PubMed:23617799}.
CC -!- DISRUPTION PHENOTYPE: Blocks TAFC biosynthesis, decreases resistance to
CC oxidative stress, and attenuates virulence in a murine model of
CC invasive pulmonary aspergillosis (PubMed:22106303).
CC {ECO:0000269|PubMed:22106303}.
CC -!- SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000010; EAL86623.1; -; Genomic_DNA.
DR RefSeq; XP_748661.1; XM_743568.1.
DR AlphaFoldDB; Q4WF54; -.
DR SMR; Q4WF54; -.
DR STRING; 746128.CADAFUBP00004399; -.
DR EnsemblFungi; EAL86623; EAL86623; AFUA_3G03410.
DR GeneID; 3506153; -.
DR KEGG; afm:AFUA_3G03410; -.
DR VEuPathDB; FungiDB:Afu3g03410; -.
DR eggNOG; KOG1680; Eukaryota.
DR HOGENOM; CLU_009834_7_6_1; -.
DR InParanoid; Q4WF54; -.
DR OMA; SLEGHMQ; -.
DR OrthoDB; 1234730at2759; -.
DR PHI-base; PHI:2322; -.
DR Proteomes; UP000002530; Chromosome 3.
DR GO; GO:0005777; C:peroxisome; IDA:AspGD.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:AspGD.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IMP:AspGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:AspGD.
DR GO; GO:1900551; P:N',N'',N'''-triacetylfusarinine C biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.12.10; -; 1.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR InterPro; IPR014748; Enoyl-CoA_hydra_C.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
PE 2: Evidence at transcript level;
KW Isomerase; Lyase; Peroxisome; Reference proteome.
FT CHAIN 1..270
FT /note="Mevalonyl-coenzyme A hydratase sidH"
FT /id="PRO_0000444396"
FT MOTIF 268..270
FT /note="PTS1-type peroxisomal targeting signal"
FT /evidence="ECO:0000269|PubMed:23617799"
SQ SEQUENCE 270 AA; 29345 MW; 8C276534BAFECAB2 CRC64;
MSTEAHPTVQ GCLVSFPTPH ILLLTLNRPE KRNCISLATS AEIQRLWTWF DTQPALYVAI
ITGTGESFCA GADLKEWNDL NARGITNEMT APGLAGLPRR RGSKPIIAAV NGYCLGGGFE
MVANCDIVVA SENATFGLPE VQRGIAAVAG SLPRLVRVLG KQRAAEIALS GLSFSASQLE
RWGLVNRVVE HDQLLATAVE IATAISRNSP DSVRVTMEGL HYGWEMASVE EASSALVDQW
YAKLMAGENF HEGVRAFVEK RKPQWRPSKL
