HXNS_EMENI
ID HXNS_EMENI Reviewed; 1350 AA.
AC A0A1U8QNG8; C8VJV8; Q5ARA2;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 1.
DT 03-AUG-2022, entry version 30.
DE RecName: Full=Nicotinate hydroxylase hnxS {ECO:0000303|PubMed:29212709};
DE EC=1.-.-.- {ECO:0000269|PubMed:29212709, ECO:0000269|PubMed:363427, ECO:0000269|PubMed:4581274};
DE AltName: Full=Nicotinate catabolism cluster protein hxnS {ECO:0000303|PubMed:363427};
DE AltName: Full=Purine hydroxylase II {ECO:0000303|PubMed:363427};
DE Short=PHII {ECO:0000303|PubMed:363427};
DE AltName: Full=Xanthine dehydrogenase II {ECO:0000303|PubMed:4581274};
GN Name=hxnS {ECO:0000303|PubMed:29212709}; ORFNames=ANIA_91782;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=4581274; DOI=10.1111/j.1432-1033.1973.tb02928.x;
RA Scazzocchio C., Holl F.B., Foguelman A.I.;
RT "The genetic control of molybdoflavoproteins in Aspergillus nidulans.
RT Allopurinol-resistant mutants constitutive for xanthine-dehydrogenase.";
RL Eur. J. Biochem. 36:428-445(1973).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=363427; DOI=10.1111/j.1432-1033.1978.tb20967.x;
RA Lewis N.J., Hurt P., Sealy-Lewis H.M., Scazzocchio C.;
RT "The genetic control of the molybdoflavoproteins in Aspergillus nidulans.
RT IV. A comparison between purine hydroxylase I and II.";
RL Eur. J. Biochem. 91:311-316(1978).
RN [5]
RP IDENTIFICATION, INDUCTION, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CATALYTIC ACTIVITY.
RX PubMed=29212709; DOI=10.1098/rsob.170199;
RA Amon J., Fernandez-Martin R., Bokor E., Cultrone A., Kelly J.M.,
RA Flipphi M., Scazzocchio C., Hamari Z.;
RT "A eukaryotic nicotinate-inducible gene cluster: convergent evolution in
RT fungi and bacteria.";
RL Open Biol. 7:0-0(2017).
CC -!- FUNCTION: Nicotinate hydroxylase, part of the hnx cluster involved in
CC the purine degradation (PubMed:4581274). The nicotinate hydroxylase
CC hnxS accepts nicotinate as a substrate and catalyzes the first step of
CC nicotinate catabolism (PubMed:4581274). HnxS accepts also hypoxanthine,
CC but not xanthine, as a substrate (PubMed:4581274, PubMed:363427,
CC PubMed:29212709). The major facilitator-type transporters hxnP and hxnZ
CC are probably involved in the uptake of nicotinate-derived metabolites,
CC and the oxidoreductases hxnT and hxnY in the further metabolism of 6-OH
CC nicotinic acid (PubMed:4581274). {ECO:0000269|PubMed:29212709,
CC ECO:0000269|PubMed:363427, ECO:0000269|PubMed:4581274}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:P80457};
CC Note=Binds 2 [2Fe-2S] clusters. {ECO:0000250|UniProtKB:P80457};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P80457};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000250|UniProtKB:P80457};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000250|UniProtKB:P80457};
CC -!- ACTIVITY REGULATION: Allopurinol inhibits catalytic activity in a
CC linear fashion (PubMed:363427). {ECO:0000269|PubMed:363427}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=90.4 uM for hypoxanthine {ECO:0000269|PubMed:363427};
CC KM=36.15 uM for 2-hydroxypurine {ECO:0000269|PubMed:363427};
CC KM=524.5 uM for 6,8-dihydroxypurine {ECO:0000269|PubMed:363427};
CC KM=188.6 uM for nicotinate {ECO:0000269|PubMed:363427};
CC pH dependence:
CC Optimum pH is 9.4. {ECO:0000269|PubMed:363427};
CC -!- INDUCTION: Expression is induced by nicotinate and 6-OH nicotinate,
CC subject to nitrogen metabolite repression mediated by the GATA factor
CC areA, and strictly regulated by the cluster-specific transcription
CC regulator hnxR (PubMed:4581274, PubMed:29212709).
CC {ECO:0000269|PubMed:29212709, ECO:0000269|PubMed:4581274}.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AACD01000170; EAA61469.1; -; Genomic_DNA.
DR EMBL; BN001306; CBF82379.1; -; Genomic_DNA.
DR RefSeq; XP_682447.1; XM_677355.1.
DR AlphaFoldDB; A0A1U8QNG8; -.
DR SMR; A0A1U8QNG8; -.
DR STRING; 162425.CADANIAP00009419; -.
DR EnsemblFungi; CBF82379; CBF82379; ANIA_09178.
DR EnsemblFungi; EAA61469; EAA61469; AN9178.2.
DR GeneID; 2868017; -.
DR KEGG; ani:AN9178.2; -.
DR eggNOG; KOG0430; Eukaryota.
DR OMA; PQAMFIA; -.
DR OrthoDB; 48717at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR002888; 2Fe-2S-bd.
DR InterPro; IPR036884; 2Fe-2S-bd_dom_sf.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR000674; Ald_Oxase/Xan_DH_a/b.
DR InterPro; IPR036856; Ald_Oxase/Xan_DH_a/b_sf.
DR InterPro; IPR016208; Ald_Oxase/xanthine_DH.
DR InterPro; IPR008274; AldOxase/xan_DH_Mopterin-bd.
DR InterPro; IPR037165; AldOxase/xan_DH_Mopterin-bd_sf.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR005107; CO_DH_flav_C.
DR InterPro; IPR036683; CO_DH_flav_C_dom_sf.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR002346; Mopterin_DH_FAD-bd.
DR PANTHER; PTHR11908; PTHR11908; 2.
DR Pfam; PF01315; Ald_Xan_dh_C; 1.
DR Pfam; PF02738; Ald_Xan_dh_C2; 1.
DR Pfam; PF03450; CO_deh_flav_C; 1.
DR Pfam; PF00941; FAD_binding_5; 1.
DR Pfam; PF01799; Fer2_2; 1.
DR PIRSF; PIRSF000127; Xanthine_DH; 1.
DR SMART; SM01008; Ald_Xan_dh_C; 1.
DR SMART; SM01092; CO_deh_flav_C; 1.
DR SUPFAM; SSF47741; SSF47741; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR SUPFAM; SSF54665; SSF54665; 1.
DR SUPFAM; SSF55447; SSF55447; 1.
DR SUPFAM; SSF56003; SSF56003; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..1350
FT /note="Nicotinate hydroxylase hnxS"
FT /id="PRO_0000443339"
FT DOMAIN 256..445
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT REGION 164..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..191
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1281
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 49
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 54
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 89
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 92
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 133
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 135
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 284..291
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 379..383
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 392
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 455
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 793
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 824
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 828
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 906
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 938
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 1107
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P80457"
SQ SEQUENCE 1350 AA; 147919 MW; 8382A423475914B2 CRC64;
MDALLPRSSP QLKFYLNGTP ISLTSPHPRW TLLDFIRSQD GLKGTKLGCG EGGCGALSGK
HVITIEGLGT VDHPHPLQER IAQLHGSQCG FCTPGIVMSL YAMIRNAYDP VTGKFQLSAD
DIESKGHLDG NLCRCTGYKP ILNAARTFIE DDLGSVPSIV ESELVGTEEE TESDMGAHSG
SGDTGSRSSG SCGRPGGCCK DSPGISSCSS RETDMTTPSL PDSPVLKQYD FIPYTPTTEL
IYPPGLAKFV PELLCYGDAE QAWVKPRSVQ EALEILSQCP SATLVTGASE VQVDVRFKDF
RPSVSVFVGD ITEMTGISWS EDMKTLYIGG SASLSDIEAE CLRCIPLLKA VNLGSESVLS
AIARTLRYFA GRQIRNAACL AGNIATASPI SDMNPLLLAV GATVHARTSA EETTIPMSEM
FKGYRKTALP SGSLITKIAV PMPSKDQIEI VNAYKQAKRK DDDIAIVTAA FRVRIAPGPD
YTVQEASLAF GGMAPTTVLA HKTASALEGK RWGDEAVLDI VLTSLGEEFN LPYSVPGGMA
TYRRTLTLSL FVRFWNYVNQ KLGLEYDSDL IEEIHRGIST GTRDDDNPHA QRVVGQQIPH
LSGLKHATGE AEYVDDMPPL HRELHGALVL SERAHAKILS VNWTPALERG AVGYVDHTSL
PEEKNHWGPV VHDEPVFAKG EVHAHGQPIG LVYADDAMTA QIAAKAVIVT YEDLPAILTI
DEAIEARSFF NYGKELRRGA PPEEIRKELD DCEYTLSGTT KIGGQEHFYL ETNAAIAVPH
TEDGSMDVWS STQNTMETQD FLSQVTNVPR HKINARVRRM GGAFGGKESR SVPIACIVAV
AAKKARRPVR IMLNRDEDMM TSGQRHPVQC RWKVGFNREG KLLVLDADTY NNAGYSVDMS
AAVMDRCLTH IENCYYIPNV WLRGWVCKTN THSNTAFRGF GAPQAMYITE SIISAVAEKV
GIDVDEIRRR NLYQVGQRTP FNQVLDEDWH VPLLLEQVRE EADYDARKKE IERFNSEHRW
RKRGIALIPT KFGISFATAL HLNQASAAVR VYTDGSVLLN HGGTEMGQGL YTKMVQVAAQ
ELRVPVDQVY TQDTSSYQTA NASPTAASSG SDLNGMAIKH ACDQINERLR PYREKYGEDA
DLGTIAKAAY RDRVNLSAAG YYKMPTIGYE WGNYSENVKP MYFYFTQRQG VACTEVELDL
LTGTHTVLRA DLKMDIGRSI NPAIDYGQIE GAFVQGQGLF TMEESLWTRS GQLATRGPGT
YKIPGFADIP QVFNSSKGIG EPPLFMGSSV LFALRDALSH ARRERGVSEP LVLDSPATVE
RLRLAVGDDL VHRAQVQRKD GEQGFFVAVA
