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2.A.40.4.1
High affinity uric acid-xanthine permease, UapA. Functionaly critical residues in transmembrane segments 1 and 3 have been identified (Amillis et al., 2011). The substrate recognition and transport pathway have been proposed (Kosti et al., 2012; Kosti et al. 2010).  UapA oligomerization is essential for membrane trafficking and turnover and is a common theme in fungi and mammalian cells (Martzoukou et al. 2015).  Specificity is determined by the interactions of a given substrate with the TMS8-9 loop and by interactions of this loop with TMS1 and TMS12 (Papageorgiou et al. 2008). F528 and Q408 in TMS 12 are important for substrate recognition, and mutation of the former results in high efficiency uptake of several purines and pyrimidines not otherwise transported (Vlanti et al. 2006). A high resolution structure of UapA is available, and it is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family (Alguel et al. 2016). The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which is a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. Alguel et al. 2016 postulated that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin.

Accession Number:Q07307
Protein Name:UapA
Length:574
Molecular Weight:61121.00
Species:Emericella nidulans (Aspergillus nidulans) [162425]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Urate, Xanthine

Cross database links:

RefSeq: XP_664536.1   
Entrez Gene ID: 2870384   
Pfam: PF00860   
KEGG: ani:AN6932.2   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005215 F:transporter activity
GO:0055085 P:transmembrane transport

References (6)

[1] “Sequence and regulation of the uapA gene encoding a uric acid-xanthine permease in the fungus Aspergillus nidulans.”  Gorfinkiel L.et.al.   8226862
[2] “The nucleobase-ascorbate transporter (NAT) signature motif in UapA defines the function of the purine translocation pathway.”  Koukaki M.et.al.   15953615
[3] “Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae.”  Galagan J.E.et.al.   16372000
[4] “Amino acid residues N450 and Q449 are critical for the uptake capacity and specificity of UapA, a prototype of a nucleobase-ascorbate transporter family.”  Meintanis C.et.al.   10824738
[5] “Transcription of purine transporter genes is activated during the isotropic growth phase of Aspergillus nidulans conidia.”  Amillis S.et.al.   15049821
[6] “Comparative substrate recognition by bacterial and fungal purine transporters of the NAT/NCS2 family.”  Goudela S.et.al.   16096268
Structure:
5i6c     

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FASTA formatted sequence
1:	MDNSIHSTDG PDSVIPNSNP KKTVRQRVRL LARHLTTREG LIGDYDYGFL FRPELPFMKK 
61:	DPRAPPFFGL NEKIPVLLAF ILGLQHALAM LAGVVTPPLI ISSSLSLPSD LQQYLVSTSL 
121:	IVCGLLSMVQ ITRFHIYKTP YYIGSGVLSV MGVSFSIISV ASGAFNQMYS NGFCQLDEAG 
181:	NRLPCPEAYG ALIGTSACCA LVEILLAFVP PKVIQKIFPP IVTGPTVMLI GISLIGTGFK 
241:	DWAGGSACMD DGMLCPSATA PRPLPWGSPE FIGLGFLVFV SIILCERFGA PIMKSCSVVI 
301:	GLLVGCIVAA ACGYFSHADI DAAPAASFIW VKTFPLSVYG PMVLPIIAVF IICACECIGD 
361:	VTATCDVSRL EVRGGTFESR IQGAVLADGI NSVVAALATM TPMTTFAQNN GVIALTRCAN 
421:	RWAGYCCCLI LIVAGIFAKF AAAIVAIPNS VMGGMKTFLF ASVVISGQAI VAKAPFTRRN 
481:	RFILTASMAL GYGATLVPTW FGNVFPQTEN RDLEGFENAI ELVLETGFAV TAFVAMLLNA 
541:	IMPAEVEEIG AVTPMPVSAH DNRDGEAEYQ SKQA