S28A3_RAT
ID S28A3_RAT Reviewed; 705 AA.
AC Q8VIH3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Solute carrier family 28 member 3;
DE AltName: Full=Concentrative Na(+)-nucleoside cotransporter 3 {ECO:0000303|Ref.1};
DE Short=CNT 3 {ECO:0000303|Ref.1};
DE Short=rCNT3 {ECO:0000303|Ref.1};
GN Name=Slc28a3; Synonyms=Cnt3 {ECO:0000303|Ref.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Pancreas;
RA Yao S.Y.M., Ng A.M.L., Loewen S.K., Cass C.E., Baldwin S.A., Young J.D.;
RT "A rat concentrative Na+-nucleoside cotransporter protein (Cnt3) broadly
RT selective for purine and pyrimidine nucleosides (system cib).";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=16014043; DOI=10.1111/j.1523-1755.2005.00444.x;
RA Rodriguez-Mulero S., Errasti-Murugarren E., Ballarin J., Felipe A.,
RA Doucet A., Casado F.J., Pastor-Anglada M.;
RT "Expression of concentrative nucleoside transporters SLC28 (CNT1, CNT2, and
RT CNT3) along the rat nephron: effect of diabetes.";
RL Kidney Int. 68:665-672(2005).
CC -!- FUNCTION: Sodium-dependent, pyrimidine- and purine-selective. Involved
CC in the homeostasis of endogenous nucleosides. Exhibits the transport
CC characteristics of the nucleoside transport system cib or N3 subtype
CC (N3/cib) (with marked transport of both thymidine and inosine). Employs
CC a 2:1 sodium/nucleoside ratio. Also able to transport gemcitabine, 3'-
CC azido-3'-deoxythymidine (AZT), ribavirin and 3-deazauridine.
CC {ECO:0000250|UniProtKB:Q9HAS3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Na(+)(out) + thymidine(out) = 2 Na(+)(in) + thymidine(in);
CC Xref=Rhea:RHEA:69899, ChEBI:CHEBI:17748, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000250|UniProtKB:Q9HAS3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(out) + 2 Na(+)(out) = cytidine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69903, ChEBI:CHEBI:17562, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000250|UniProtKB:Q9HAS3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Na(+)(out) + uridine(out) = 2 Na(+)(in) + uridine(in);
CC Xref=Rhea:RHEA:69907, ChEBI:CHEBI:16704, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000250|UniProtKB:Q9HAS3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine(out) + 2 Na(+)(out) = adenosine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69911, ChEBI:CHEBI:16335, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000250|UniProtKB:Q9HAS3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine(out) + 2 Na(+)(out) = guanosine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69915, ChEBI:CHEBI:16750, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000250|UniProtKB:Q9HAS3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine(out) + 2 Na(+)(out) = inosine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69919, ChEBI:CHEBI:17596, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000250|UniProtKB:Q9HAS3};
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q9HAS3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9HAS3};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney; in the proximal tubule,
CC glomerulus and cortical collecting duct. {ECO:0000269|PubMed:16014043}.
CC -!- SIMILARITY: Belongs to the concentrative nucleoside transporter (CNT)
CC (TC 2.A.41) family. {ECO:0000305}.
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DR EMBL; AY059414; AAL27091.1; -; mRNA.
DR RefSeq; NP_543184.1; NM_080908.1.
DR AlphaFoldDB; Q8VIH3; -.
DR SMR; Q8VIH3; -.
DR STRING; 10116.ENSRNOP00000025745; -.
DR PaxDb; Q8VIH3; -.
DR GeneID; 140944; -.
DR KEGG; rno:140944; -.
DR UCSC; RGD:621224; rat.
DR CTD; 64078; -.
DR RGD; 621224; Slc28a3.
DR eggNOG; KOG3747; Eukaryota.
DR InParanoid; Q8VIH3; -.
DR PhylomeDB; Q8VIH3; -.
DR Reactome; R-RNO-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR Reactome; R-RNO-9748787; Azathioprine ADME.
DR PRO; PR:Q8VIH3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005415; F:nucleoside:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0015390; F:purine-specific nucleoside:sodium symporter activity; ISO:RGD.
DR GO; GO:0015389; F:pyrimidine- and adenine-specific:sodium symporter activity; ISO:RGD.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0015213; F:uridine transmembrane transporter activity; ISO:RGD.
DR GO; GO:1901642; P:nucleoside transmembrane transport; ISO:RGD.
DR GO; GO:0015860; P:purine nucleoside transmembrane transport; ISO:RGD.
DR GO; GO:0015864; P:pyrimidine nucleoside transport; ISO:RGD.
DR GO; GO:0072531; P:pyrimidine-containing compound transmembrane transport; ISO:RGD.
DR GO; GO:0001895; P:retina homeostasis; IDA:RGD.
DR GO; GO:0015862; P:uridine transport; ISO:RGD.
DR InterPro; IPR008276; C_nuclsd_transpt.
DR InterPro; IPR018270; C_nuclsd_transpt_met_bac.
DR InterPro; IPR030211; CNT3.
DR InterPro; IPR011657; CNT_C_dom.
DR InterPro; IPR002668; CNT_N_dom.
DR InterPro; IPR011642; Gate_dom.
DR PANTHER; PTHR10590; PTHR10590; 1.
DR PANTHER; PTHR10590:SF18; PTHR10590:SF18; 1.
DR Pfam; PF07670; Gate; 1.
DR Pfam; PF07662; Nucleos_tra2_C; 1.
DR Pfam; PF01773; Nucleos_tra2_N; 1.
DR TIGRFAMs; TIGR00804; nupC; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Membrane; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..705
FT /note="Solute carrier family 28 member 3"
FT /id="PRO_0000324148"
FT TOPO_DOM 1..119
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 120..140
FT /note="Helical; Name=TM1"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 141..145
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 146..166
FT /note="Helical; Name=TM2"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 167..190
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 191..211
FT /note="Helical; Name=TM3"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 212..214
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 215..236
FT /note="Helical; Name=TM4"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 237..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 245..264
FT /note="Helical; Name=TM5"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 265..301
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 302..322
FT /note="Helical; Name=TM6"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 323..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 347..365
FT /note="Helical; Name=HP1"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 366..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 379..401
FT /note="Helical; Name=TM7"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 402..403
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 404..425
FT /note="Helical; Name=TM8"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 426..460
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 461..486
FT /note="Helical; Name=TM9"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 487..524
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 525..544
FT /note="Helical; Name=HP2"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 545..583
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 584..594
FT /note="Helical; Name=TM10"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 595..607
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 608..630
FT /note="Helical; Name=TM11"
FT /evidence="ECO:0000250|UniProtKB:Q9HAS3"
FT TOPO_DOM 631..705
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..96
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 705 AA; 78374 MW; 5DF4B4AC3C416BE6 CRC64;
MSRSDPDPGK NSEPSKSKMS LELRPTAPSD QGRLNEAFQD EDLEEQNAPG NSTVRSRVVQ
SGEQGRAKQD DRQITIEQEP LGPKEGTEEE SEDERQKGFL ERKYDTVCEF CRKHRVILQH
TIWAVLLTGF LALVIAACAL NFHRALPLFV ITLVTIFFVV WDRLMAKYEQ RIDDVLSPGK
RLLERHWFWL KWVVWCSLIL AVILWLALDT ARLGQQQLIS FGGLVMYIVL LFLFSKHPTR
VYWRPVFWGI GLQFLLGLLI LRTRPGFVAF DWMGKQVQTF LGYTDAGAQF VFGEKYTDHF
FAFKILPIVV FFSTVMSMLY YLGLMQWIIR KVGWLMLVTM GSSPIESVVA AGNIFVGQTE
SPLLVQPYLP HVTKSELHTI MTAGFATIAG SVLGAYISFG VSSTHLLTAS VMSAPAALAV
AKLFWPETEK PKITLKNAMK MENGDSRNLL EAATQGASSS IPLVANIAAN LIAFLALLSF
VNSALSWFGS MFDYPQLSFE LICSYIFMPF SFMMGVDWQD RFMVAKLIGY KTFFNEFVAY
EHLSKFINLR KAAGPKFVNG VQQYMSIRSE TIATYALCGF ANFGSLGIVI GGLTSIAPSR
KRDIASGAMR ALIAGTIACF MTACIAGMLS DTPVAINCHH VLESSKVLSN TTEVASCCQG
LFNSTVARGP NDVLPGGNFS LYTLKSCCNL LKPPTLNCGW IPNIP