UAPA_EMENI
ID UAPA_EMENI Reviewed; 574 AA.
AC Q07307; C8V364; Q5AXP8;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 3.
DT 25-MAY-2022, entry version 120.
DE RecName: Full=Uric acid-xanthine permease;
DE AltName: Full=UAPA transporter;
GN Name=uapA; ORFNames=AN6932;
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 [GENOMIC DNA], AND INDUCTION.
RX PubMed=8226862; DOI=10.1016/s0021-9258(19)49473-8;
RA Gorfinkiel L., Diallinas G., Scazzocchio C.;
RT "Sequence and regulation of the uapA gene encoding a uric acid-xanthine
RT permease in the fungus Aspergillus nidulans.";
RL J. Biol. Chem. 268:23376-23381(1993).
RN [2]
RP SEQUENCE REVISION TO N-TERMINUS; 57-58; 65; 164 AND 191, FUNCTION, AND
RP MUTAGENESIS OF GLN-408; ASN-409; GLY-411; THR-416; ARG-417; ASN-420 AND
RP ARG-421.
RX PubMed=15953615; DOI=10.1016/j.jmb.2005.04.076;
RA Koukaki M., Vlanti A., Goudela S., Pantazopoulou A., Gioule H.,
RA Tournaviti S., Diallinas G.;
RT "The nucleobase-ascorbate transporter (NAT) signature motif in UapA defines
RT the function of the purine translocation pathway.";
RL J. Mol. Biol. 350:499-513(2005).
RN [3]
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 [4]
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 [5]
RP MUTAGENESIS OF PHE-406; GLN-408; ASN-409 AND THR-416.
RX PubMed=10824738; DOI=10.1080/096876800294489;
RA Meintanis C., Karagouni A.D., Diallinas G.;
RT "Amino acid residues N450 and Q449 are critical for the uptake capacity and
RT specificity of UapA, a prototype of a nucleobase-ascorbate transporter
RT family.";
RL Mol. Membr. Biol. 17:47-57(2000).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=15049821; DOI=10.1046/j.1365-2958.2003.03956.x;
RA Amillis S., Cecchetto G., Sophianopoulou V., Koukaki M., Scazzocchio C.,
RA Diallinas G.;
RT "Transcription of purine transporter genes is activated during the
RT isotropic growth phase of Aspergillus nidulans conidia.";
RL Mol. Microbiol. 52:205-216(2004).
RN [7]
RP FUNCTION.
RX PubMed=16096268; DOI=10.1080/09687860500093016;
RA Goudela S., Karatza P., Koukaki M., Frillingos S., Diallinas G.;
RT "Comparative substrate recognition by bacterial and fungal purine
RT transporters of the NAT/NCS2 family.";
RL Mol. Membr. Biol. 22:263-275(2005).
RN [8]
RP SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF GLN-408 AND GLY-411, AND
RP UBIQUITINATION AT LYS-572.
RX PubMed=20002879; DOI=10.1111/j.1365-2958.2009.06997.x;
RA Gournas C., Amillis S., Vlanti A., Diallinas G.;
RT "Transport-dependent endocytosis and turnover of a uric acid-xanthine
RT permease.";
RL Mol. Microbiol. 75:246-260(2010).
CC -!- FUNCTION: Uric acid-xanthine transporter. {ECO:0000269|PubMed:15953615,
CC ECO:0000269|PubMed:16096268, ECO:0000269|PubMed:20002879}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20002879};
CC Multi-pass membrane protein {ECO:0000269|PubMed:20002879}.
CC -!- DEVELOPMENTAL STAGE: Not detected in resting conidiospores.
CC Transcription is activated during the isotropic growth phase of
CC conidiospores. {ECO:0000269|PubMed:15049821}.
CC -!- INDUCTION: Inducible by 2-thiouric acid, and highly repressible by
CC ammonium. {ECO:0000269|PubMed:8226862}.
CC -!- PTM: Ubiquitinated by hulA. Ubiquitination leads to internalization,
CC sorting into the endosomal pathway to the vacuolar lumen where uapA is
CC eventually degraded. {ECO:0000269|PubMed:20002879}.
CC -!- SIMILARITY: Belongs to the nucleobase:cation symporter-2 (NCS2) (TC
CC 2.A.40) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CBF71770.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAA57687.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X71807; CAA50681.2; -; Genomic_DNA.
DR EMBL; AACD01000115; EAA57687.1; ALT_INIT; Genomic_DNA.
DR EMBL; BN001301; CBF71770.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_664536.1; XM_659444.1.
DR PDB; 5I6C; X-ray; 3.70 A; A/B=1-574.
DR PDBsum; 5I6C; -.
DR AlphaFoldDB; Q07307; -.
DR SMR; Q07307; -.
DR STRING; 162425.CADANIAP00007742; -.
DR ChEMBL; CHEMBL4295591; -.
DR TCDB; 2.A.40.4.1; the nucleobase/ascorbate transporter (nat) or nucleobase:cation symporter-2 (ncs2) family.
DR iPTMnet; Q07307; -.
DR EnsemblFungi; EAA57687; EAA57687; AN6932.2.
DR GeneID; 2870384; -.
DR KEGG; ani:AN6932.2; -.
DR VEuPathDB; FungiDB:AN6932; -.
DR eggNOG; ENOG502QQD4; Eukaryota.
DR HOGENOM; CLU_017959_7_0_1; -.
DR InParanoid; Q07307; -.
DR OrthoDB; 387031at2759; -.
DR Proteomes; UP000000560; Chromosome I.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0034423; C:autophagosome lumen; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0000324; C:fungal-type vacuole; IDA:AspGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0002060; F:purine nucleobase binding; IDA:AspGD.
DR GO; GO:0015143; F:urate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0042907; F:xanthine transmembrane transporter activity; IDA:AspGD.
DR GO; GO:0015747; P:urate transport; IDA:UniProtKB.
DR GO; GO:0042906; P:xanthine transport; IDA:AspGD.
DR InterPro; IPR006043; NCS2.
DR InterPro; IPR006042; Xan_ur_permease.
DR Pfam; PF00860; Xan_ur_permease; 1.
DR TIGRFAMs; TIGR00801; ncs2; 1.
DR PROSITE; PS01116; XANTH_URACIL_PERMASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Isopeptide bond; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..574
FT /note="Uric acid-xanthine permease"
FT /id="PRO_0000165952"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..361
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 427..447
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..542
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 572
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20002879"
FT MUTAGEN 406
FT /note="F->Y: No effect."
FT /evidence="ECO:0000269|PubMed:10824738"
FT MUTAGEN 408
FT /note="Q->A,N,P,S: Decreased affinity for xanthine and uric
FT acid."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615, ECO:0000269|PubMed:20002879"
FT MUTAGEN 408
FT /note="Q->E: Does not significantly affect substrate
FT affinities at 37 degrees Celsius but has no uptake activity
FT at 25 degrees Celsius. Confers moderate binding affinity
FT for hypoxanthine, guanine and 7-deazanthine, enhances
FT binding affinity for 8-azaxanthine and 8-thiouric acid."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615, ECO:0000269|PubMed:20002879"
FT MUTAGEN 409
FT /note="N->A: Does not significantly affect substrate
FT affinities at 37 degrees Celsius but has no uptake activity
FT at 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 409
FT /note="N->D: Total loss of function."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 409
FT /note="N->Q: Increases affinity for xanthine, but not uric
FT acid, 9-methylxanthine or 8-azaxanthine."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 409
FT /note="N->S: Does not significantly affect substrate
FT affinities at 37 degrees Celsius but has no uptake activity
FT at 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 411
FT /note="G->A: Decreases affinity for uric acid significantly
FT more than affinity for xanthine. Confers ability to grow on
FT hypoxanthine."
FT /evidence="ECO:0000269|PubMed:15953615,
FT ECO:0000269|PubMed:20002879"
FT MUTAGEN 411
FT /note="G->P: Decreases affinity for uric acid
FT significantly. Increases affinity for xanthine, 3-
FT methylxanthine, 2-methylxanthine, 2-thioxanthine, 6-
FT thioxanthine, oxypurinol and 8-thiouric acid. Confers
FT ability to grow on hypoxanthine."
FT /evidence="ECO:0000269|PubMed:15953615,
FT ECO:0000269|PubMed:20002879"
FT MUTAGEN 411
FT /note="G->V: Total loss of function."
FT /evidence="ECO:0000269|PubMed:15953615,
FT ECO:0000269|PubMed:20002879"
FT MUTAGEN 416
FT /note="T->A,S: Does not significantly affect substrate
FT affinities."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 416
FT /note="T->D: Does not significantly affect substrate
FT affinities at 37 degrees Celsius but has no uptake activity
FT at 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 416
FT /note="T->N: Decreases affinity for uric acid significantly
FT more than affinity for xanthine. Confers ability to grow on
FT hypoxanthine."
FT /evidence="ECO:0000269|PubMed:10824738,
FT ECO:0000269|PubMed:15953615"
FT MUTAGEN 417
FT /note="R->G: Decreases affinity for uric acid significantly
FT more than affinity for xanthine."
FT /evidence="ECO:0000269|PubMed:15953615"
FT MUTAGEN 417
FT /note="R->K: Does not significantly affect substrate
FT affinities."
FT /evidence="ECO:0000269|PubMed:15953615"
FT MUTAGEN 420
FT /note="N->S: Does not significantly affect substrate
FT affinities at 37 degrees Celsius but has no uptake activity
FT at 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:15953615"
FT MUTAGEN 421
FT /note="R->T,V: Decreases affinity for uric acid
FT significantly more than affinity for xanthine."
FT /evidence="ECO:0000269|PubMed:15953615"
SQ SEQUENCE 574 AA; 61121 MW; 7CFF53D3DF781E3B CRC64;
MDNSIHSTDG PDSVIPNSNP KKTVRQRVRL LARHLTTREG LIGDYDYGFL FRPELPFMKK
DPRAPPFFGL NEKIPVLLAF ILGLQHALAM LAGVVTPPLI ISSSLSLPSD LQQYLVSTSL
IVCGLLSMVQ ITRFHIYKTP YYIGSGVLSV MGVSFSIISV ASGAFNQMYS NGFCQLDEAG
NRLPCPEAYG ALIGTSACCA LVEILLAFVP PKVIQKIFPP IVTGPTVMLI GISLIGTGFK
DWAGGSACMD DGMLCPSATA PRPLPWGSPE FIGLGFLVFV SIILCERFGA PIMKSCSVVI
GLLVGCIVAA ACGYFSHADI DAAPAASFIW VKTFPLSVYG PMVLPIIAVF IICACECIGD
VTATCDVSRL EVRGGTFESR IQGAVLADGI NSVVAALATM TPMTTFAQNN GVIALTRCAN
RWAGYCCCLI LIVAGIFAKF AAAIVAIPNS VMGGMKTFLF ASVVISGQAI VAKAPFTRRN
RFILTASMAL GYGATLVPTW FGNVFPQTEN RDLEGFENAI ELVLETGFAV TAFVAMLLNA
IMPAEVEEIG AVTPMPVSAH DNRDGEAEYQ SKQA
