S29A4_MOUSE
ID S29A4_MOUSE Reviewed; 528 AA.
AC Q8R139;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Equilibrative nucleoside transporter 4;
DE AltName: Full=Solute carrier family 29 member 4;
GN Name=Slc29a4; Synonyms=Ent4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP FUNCTION, TISSUE SPECIFICITY, AND GLYCOSYLATION AT ASN-521.
RX PubMed=16873718; DOI=10.1161/01.res.0000238359.18495.42;
RA Barnes K., Dobrzynski H., Foppolo S., Beal P.R., Ismat F., Scullion E.R.,
RA Sun L., Tellez J., Ritzel M.W., Claycomb W.C., Cass C.E., Young J.D.,
RA Billeter-Clark R., Boyett M.R., Baldwin S.A.;
RT "Distribution and functional characterization of equilibrative nucleoside
RT transporter-4, a novel cardiac adenosine transporter activated at acidic
RT pH.";
RL Circ. Res. 99:510-519(2006).
CC -!- FUNCTION: Functions as a polyspecific organic cation transporter,
CC efficiently transporting many organic cations such as monoamine
CC neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines
CC including serotonin, dopamine, norepinephrine and epinephrine. May play
CC a role in regulating central nervous system homeostasis of monoamine
CC neurotransmitters. May be involved in luminal transport of organic
CC cations in the kidney and seems to use luminal proton gradient to drive
CC organic cation reabsorptprev reabsorption. Does not seem to transport
CC nucleoside and nucleoside analogs such as uridine, cytidine, thymidine,
CC adenosine, inosine, guanosine, and azidothymidine. In (PubMed:16873718)
CC adenosine is efficiently transported but in a fashion highly sensitive
CC to extracellular pH, with maximal activity in the pH range 5.5 to 6.5.
CC Glu-206 is essential for the cation selectivity and may function as the
CC charge sensor for cationic substrates. Transport is chloride and
CC sodium-independent but appears to be sensitive to changes in membrane
CC potential. Weakly inhibited by the classical inhibitors of
CC equilibrative nucleoside transport, dipyridamole, dilazep, and
CC nitrobenzylthioinosine. May play a role in the regulation of
CC extracellular adenosine concentrations in cardiac tissues, in
CC particular during ischemia (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:16873718}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Apical cell membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}. Note=Located to the plasma membranes of
CC ventricular myocytes and vascular endothelial cells. Targeted to the
CC apical membranes of differentiated kidney epithelial cells (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in heart. {ECO:0000269|PubMed:16873718}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16873718}.
CC -!- SIMILARITY: Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
CC {ECO:0000305}.
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DR EMBL; BC025599; AAH25599.1; -; mRNA.
DR CCDS; CCDS39364.1; -.
DR RefSeq; NP_666369.1; NM_146257.2.
DR RefSeq; XP_006504769.1; XM_006504706.2.
DR AlphaFoldDB; Q8R139; -.
DR SMR; Q8R139; -.
DR STRING; 10090.ENSMUSP00000059896; -.
DR GlyGen; Q8R139; 1 site.
DR iPTMnet; Q8R139; -.
DR PhosphoSitePlus; Q8R139; -.
DR PaxDb; Q8R139; -.
DR PRIDE; Q8R139; -.
DR ProteomicsDB; 256878; -.
DR Antibodypedia; 24590; 258 antibodies from 25 providers.
DR DNASU; 243328; -.
DR Ensembl; ENSMUST00000058418; ENSMUSP00000059896; ENSMUSG00000050822.
DR GeneID; 243328; -.
DR KEGG; mmu:243328; -.
DR UCSC; uc009aiz.1; mouse.
DR CTD; 222962; -.
DR MGI; MGI:2385330; Slc29a4.
DR VEuPathDB; HostDB:ENSMUSG00000050822; -.
DR eggNOG; KOG1479; Eukaryota.
DR GeneTree; ENSGT00950000182898; -.
DR HOGENOM; CLU_021611_4_0_1; -.
DR InParanoid; Q8R139; -.
DR OMA; FDMSVVY; -.
DR OrthoDB; 674800at2759; -.
DR PhylomeDB; Q8R139; -.
DR TreeFam; TF313950; -.
DR Reactome; R-MMU-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR BioGRID-ORCS; 243328; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Slc29a4; mouse.
DR PRO; PR:Q8R139; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8R139; protein.
DR Bgee; ENSMUSG00000050822; Expressed in embryonic brain and 100 other tissues.
DR ExpressionAtlas; Q8R139; baseline and differential.
DR Genevisible; Q8R139; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0008324; F:cation transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; ISO:MGI.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0005342; F:organic acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; ISO:MGI.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISO:MGI.
DR GO; GO:0098655; P:cation transmembrane transport; IMP:ARUK-UCL.
DR GO; GO:0090494; P:dopamine uptake; IMP:ARUK-UCL.
DR GO; GO:0051625; P:epinephrine uptake; ISO:MGI.
DR GO; GO:0140115; P:export across plasma membrane; ISO:MGI.
DR GO; GO:0051615; P:histamine uptake; ISO:MGI.
DR GO; GO:0015844; P:monoamine transport; ISO:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; IMP:ARUK-UCL.
DR GO; GO:0051620; P:norepinephrine uptake; IMP:ARUK-UCL.
DR GO; GO:1903825; P:organic acid transmembrane transport; ISO:MGI.
DR GO; GO:0015695; P:organic cation transport; ISO:MGI.
DR GO; GO:0051610; P:serotonin uptake; IMP:ARUK-UCL.
DR GO; GO:1901998; P:toxin transport; IMP:ARUK-UCL.
DR GO; GO:0042908; P:xenobiotic transport; IMP:ARUK-UCL.
DR InterPro; IPR030198; ENT4.
DR InterPro; IPR002259; Eqnu_transpt.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR10332; PTHR10332; 1.
DR PANTHER; PTHR10332:SF4; PTHR10332:SF4; 1.
DR Pfam; PF01733; Nucleoside_tran; 1.
DR PIRSF; PIRSF016379; ENT; 1.
DR PRINTS; PR01130; DERENTRNSPRT.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..528
FT /note="Equilibrative nucleoside transporter 4"
FT /id="PRO_0000326252"
FT TOPO_DOM 1..68
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..139
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..231
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 368..376
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..411
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 433..445
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 467..481
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 521
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16873718"
SQ SEQUENCE 528 AA; 58099 MW; 96379B4FBB2AD2ED CRC64;
MGSIGSQRLK EPCVAATSDQ SVVTSFSFDN FQLETTAEGA QDPGIRVRGV PTFTDSAVEE
PVPDDRYHAI YFAMLLAGVG FLLPYNSFIT DVDYLHHKYP GTSIVFDMSL TYILVALAAV
LLNNVVVERL NLHTRITTGY LLALGPLLFI SICDVWLQLF SHDQAYAINL AAVGTVAFGC
TVQQSSFYGY TGLLPKRYTQ GVMTGESTAG VMISLSRILT KLLLPDERAS TIIFFLVSAG
LELLCFLLHL LVRRSRFVLY YTTRPRDSRP VQAGYRVHHD VASGDIHFEH QTPALSSSRS
PKESPAHEVT HSNSGVYMRF DVPRPRVKRS WPTFRALLLH RYVVARVIWA DMLSIAVTYF
ITLCLFPGLE SEIRHCVLGE WLPILVMAVF NLSDFVGKIL AALPVEWRGT HLLACSCLRV
VFIPLFILCV YPSGMPALRH PAWPCVFSLL MGISNGYFGS VPMILAAGKV SPKQRELAGN
TMTVSYMSGL TLGSAVAYCT YSLTRDAHGS CFQTATAAAA NDSIPVGP
