ID   S28A1_RAT               Reviewed;         648 AA.
AC   Q62674;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 133.
DE   RecName: Full=Sodium/nucleoside cotransporter 1 {ECO:0000305|PubMed:8027026};
DE   AltName: Full=Concentrative nucleoside transporter 1 {ECO:0000303|PubMed:11375981};
DE            Short=CNT 1 {ECO:0000303|PubMed:11375981};
DE   AltName: Full=Na(+)/nucleoside cotransporter 1 {ECO:0000303|PubMed:11375981};
DE   AltName: Full=Sodium-coupled nucleoside transporter 1;
DE   AltName: Full=Solute carrier family 28 member 1 {ECO:0000312|RGD:621223};
GN   Name=Slc28a1 {ECO:0000312|RGD:621223};
GN   Synonyms=Cnt1 {ECO:0000303|PubMed:11375981};
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], FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR
RP   LOCATION.
RC   STRAIN=Sprague-Dawley; TISSUE=Jejunum;
RX   PubMed=8027026; DOI=10.1016/s0021-9258(17)32370-0;
RA   Huang Q.-Q., Yao S.Y.M., Ritzel M.W.L., Paterson A.R.P., Cass C.E.,
RA   Young J.D.;
RT   "Cloning and functional expression of a complementary DNA encoding a
RT   mammalian nucleoside transport protein.";
RL   J. Biol. Chem. 269:17757-17760(1994).
RN   [2]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=8967974;
RA   Yao S.Y., Ng A.M., Ritzel M.W., Gati W.P., Cass C.E., Young J.D.;
RT   "Transport of adenosine by recombinant purine- and pyrimidine-selective
RT   sodium/nucleoside cotransporters from rat jejunum expressed in Xenopus
RT   laevis oocytes.";
RL   Mol. Pharmacol. 50:1529-1535(1996).
RN   [3]
RP   TOPOLOGY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION AT
RP   ASN-605 AND ASN-643.
RX   PubMed=11375981; DOI=10.1074/jbc.m100518200;
RA   Hamilton S.R., Yao S.Y., Ingram J.C., Hadden D.A., Ritzel M.W.,
RA   Gallagher M.P., Henderson P.J., Cass C.E., Young J.D., Baldwin S.A.;
RT   "Subcellular distribution and membrane topology of the mammalian
RT   concentrative Na+-nucleoside cotransporter rCNT1.";
RL   J. Biol. Chem. 276:27981-27988(2001).
CC   -!- FUNCTION: Sodium and pyrimidine nucleoside symporter of the plasma
CC       membrane that imports uridine, thymidine and cytidine into cells by
CC       coupling their transport to the transmembrane sodium electrochemical
CC       gradient. Also transports adenosine, an atypical substrate transported
CC       with high apparent affinity, but low maximum velocity. Therefore,
CC       exhibits the transport characteristics of the nucleoside transport
CC       system cit or N2 subtype (N2/cit) (PubMed:8027026, PubMed:8967974).
CC       Involved in renal nucleoside (re)absorption (By similarity).
CC       {ECO:0000250|UniProtKB:O00337, ECO:0000269|PubMed:8027026,
CC       ECO:0000269|PubMed:8967974}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Na(+)(out) + uridine(out) = Na(+)(in) + uridine(in);
CC         Xref=Rhea:RHEA:69887, ChEBI:CHEBI:16704, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:8027026};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Na(+)(out) + thymidine(out) = Na(+)(in) + thymidine(in);
CC         Xref=Rhea:RHEA:69891, ChEBI:CHEBI:17748, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:8027026};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cytidine(out) + Na(+)(out) = cytidine(in) + Na(+)(in);
CC         Xref=Rhea:RHEA:69895, ChEBI:CHEBI:17562, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:8027026};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=adenosine(out) + Na(+)(out) = adenosine(in) + Na(+)(in);
CC         Xref=Rhea:RHEA:69927, ChEBI:CHEBI:16335, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:8027026, ECO:0000269|PubMed:8967974};
CC   -!- ACTIVITY REGULATION: Due to its high apparent affinity but slow
CC       transport, adenosine could act as a negative regulator of pyrimidine
CC       transport under some conditions. {ECO:0000250|UniProtKB:O00337}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11375981,
CC       ECO:0000269|PubMed:8027026, ECO:0000269|PubMed:8967974}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:11375981}. Apical cell membrane
CC       {ECO:0000250|UniProtKB:O00337}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:11375981}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in the brush-border
CC       membranes of the polarized epithelial cells of jejunum and renal
CC       cortical tubules and in the bile canalicular membranes of liver
CC       parenchymal cells. {ECO:0000269|PubMed:11375981}.
CC   -!- PTM: N-glycosylated. N-glycosylation is required for localization to
CC       the plasma membrane and the transporter activity.
CC       {ECO:0000269|PubMed:11375981}.
CC   -!- SIMILARITY: Belongs to the concentrative nucleoside transporter (CNT)
CC       (TC 2.A.41) family. {ECO:0000305}.
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DR   EMBL; U10279; AAB03626.1; -; mRNA.
DR   PIR; A54892; A54892.
DR   RefSeq; NP_446315.1; NM_053863.1.
DR   AlphaFoldDB; Q62674; -.
DR   SMR; Q62674; -.
DR   STRING; 10116.ENSRNOP00000070095; -.
DR   ChEMBL; CHEMBL1287615; -.
DR   TCDB; 2.A.41.2.2; the concentrative nucleoside transporter (cnt) family.
DR   GlyCosmos; Q62674; 2 sites, No reported glycans.
DR   GlyGen; Q62674; 2 sites.
DR   iPTMnet; Q62674; -.
DR   PhosphoSitePlus; Q62674; -.
DR   PaxDb; 10116-ENSRNOP00000025621; -.
DR   Ensembl; ENSRNOT00055015037; ENSRNOP00055012004; ENSRNOG00055008906.
DR   Ensembl; ENSRNOT00060006165; ENSRNOP00060004574; ENSRNOG00060003724.
DR   Ensembl; ENSRNOT00065053624; ENSRNOP00065044072; ENSRNOG00065031108.
DR   GeneID; 116642; -.
DR   KEGG; rno:116642; -.
DR   AGR; RGD:621223; -.
DR   CTD; 9154; -.
DR   RGD; 621223; Slc28a1.
DR   eggNOG; KOG3747; Eukaryota.
DR   InParanoid; Q62674; -.
DR   OrthoDB; 1333063at2759; -.
DR   PhylomeDB; Q62674; -.
DR   Reactome; R-RNO-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR   PRO; PR:Q62674; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR   GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:1901474; F:azole transmembrane transporter activity; ISO:RGD.
DR   GO; GO:0005350; F:pyrimidine nucleobase transmembrane transporter activity; IDA:RGD.
DR   GO; GO:0015389; F:pyrimidine- and adenosine-specific:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0015213; F:uridine transmembrane transporter activity; ISO:RGD.
DR   GO; GO:0045117; P:azole transmembrane transport; ISO:RGD.
DR   GO; GO:0015861; P:cytidine transport; ISS:UniProtKB.
DR   GO; GO:0180015; P:nucleoside import across plasma membrane; ISS:UniProtKB.
DR   GO; GO:1901642; P:nucleoside transmembrane transport; ISO:RGD.
DR   GO; GO:0015855; P:pyrimidine nucleobase transport; IDA:RGD.
DR   GO; GO:0072531; P:pyrimidine-containing compound transmembrane transport; ISO:RGD.
DR   GO; GO:0015862; P:uridine transport; ISS:UniProtKB.
DR   InterPro; IPR008276; C_nuclsd_transpt.
DR   InterPro; IPR018270; C_nuclsd_transpt_met_bac.
DR   InterPro; IPR011657; CNT_C_dom.
DR   InterPro; IPR002668; CNT_N_dom.
DR   InterPro; IPR011642; Gate_dom.
DR   NCBIfam; TIGR00804; nupC; 1.
DR   PANTHER; PTHR10590; SODIUM/NUCLEOSIDE COTRANSPORTER; 1.
DR   PANTHER; PTHR10590:SF16; SODIUM_NUCLEOSIDE COTRANSPORTER 1; 1.
DR   Pfam; PF07670; Gate; 1.
DR   Pfam; PF07662; Nucleos_tra2_C; 1.
DR   Pfam; PF01773; Nucleos_tra2_N; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Glycoprotein; Membrane; Reference proteome; Symport;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..648
FT                   /note="Sodium/nucleoside cotransporter 1"
FT                   /id="PRO_0000070449"
FT   TOPO_DOM        1..80
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        81..104
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        105..109
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        110..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        129..147
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        148..167
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        168..178
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        179..195
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        196..201
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        202..222
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        223..261
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        262..283
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        284..294
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        295..318
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        319..337
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        338..360
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        361..366
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        367..386
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        387..423
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        424..446
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        447..457
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        458..479
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        480..534
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        535..558
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        559..569
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   TRANSMEM        570..592
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        593..648
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   CARBOHYD        605
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11375981"
FT   CARBOHYD        643
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11375981"
SQ   SEQUENCE   648 AA;  71001 MW;  7618B4436DAED1A8 CRC64;
     MADNTQRQRE SISLTPMAHG LENMGAEFLE SMEEGRLPHS HSSLPEGEGG LNKAERKAFS
     RWRSLQPTVQ ARSFCREHRQ LFGWICKGLL STACLGFLMV ACLLDLQRAL ALLIITCVVL
     VFLAYDLLKR LLGSKLRRCV KFQGHSCLSL WLKRGLALAA GVGLILWLSL DTAQRPEQLV
     SFAGICVFLV LLFAGSKHHR AVSWRAVSWG LGLQFVLGLF VIRTEPGFIA FQWLGDQIQV
     FLSYTEAGSS FVFGEALVKD VFAFQVLPII IFFSCVMSVL YYLGLMQWVI LKIAWLMQVT
     MGTSATETLS VAGNIFVSQT EAPLLIRPYL ADMTLSEVHV VMTGGYATIA GSLLGAYISF
     GIDAASLIAA SVMAAPCALA LSKLVYPEVE ESKFRSENGV KLTYGDAQNL LEAASAGAAI
     SVKVVANIAA NLIAFLAVLA FVNAALSWLG DMVDIQGLSF QLICSYVLRP VAFLMGVAWE
     DCPVVAELLG IKFFLNEFVA YQELSQYKQR RLAGAEEWLG DKKQWISVRA EILTTYALCG
     FANFSSIGIM LGGLTSLVPQ RRSDFSQIVL RALITGAFVS LLNACVAGIL YVPRGVEVDC
     VSLLNQTVSS SSFEVYLCCR QVFQSTSSEF SQVALDNCCR FYNHTVCT
//