Full text data of SLC29A1
SLC29A1
(ENT1)
[Confidence: high (present in two of the MS resources)]
Equilibrative nucleoside transporter 1 (Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter; Equilibrative NBMPR-sensitive nucleoside transporter; Nucleoside transporter, es-type; Solute carrier family 29 member 1)
Equilibrative nucleoside transporter 1 (Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter; Equilibrative NBMPR-sensitive nucleoside transporter; Nucleoside transporter, es-type; Solute carrier family 29 member 1)
UniProt
Q99808
ID S29A1_HUMAN Reviewed; 456 AA.
AC Q99808; B3KQY5; Q5T9W9; Q9UJY2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Equilibrative nucleoside transporter 1;
DE AltName: Full=Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter;
DE Short=Equilibrative NBMPR-sensitive nucleoside transporter;
DE AltName: Full=Nucleoside transporter, es-type;
DE AltName: Full=Solute carrier family 29 member 1;
GN Name=SLC29A1; Synonyms=ENT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-22.
RC TISSUE=Placenta;
RX PubMed=8986748; DOI=10.1038/nm0197-89;
RA Griffiths M., Beaumont N., Yao S.Y.M., Sundaram M., Boumah C.E.,
RA Davies A., Kwong F.Y.P., Coe I., Cass C.E., Young J.D., Baldwin S.A.;
RT "Cloning of a human nucleoside transporter implicated in the cellular
RT uptake of adenosine and chemotherapeutic drugs.";
RL Nat. Med. 3:89-93(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Graham K.A., Coe I.R., Carpenter P., Baldwin S.A., Young J.D.,
RA Cass C.E.;
RT "Genomic sequence of the human equilibrative nucleoside transporter 1
RT (hENT1).";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Jejunum, and Small intestine;
RX PubMed=10755314; DOI=10.1007/s002800050040;
RA Lum P.Y., Ngo L.Y., Bakken A.H., Unadkat J.D.;
RT "Human intestinal es nucleoside transporter: molecular
RT characterization and nucleoside inhibitory profiles.";
RL Cancer Chemother. Pharmacol. 45:273-278(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12384580; DOI=10.1093/nar/gkf564;
RA Sankar N., Machado J., Abdulla P., Hilliker A.J., Coe I.R.;
RT "Comparative genomic analysis of equilibrative nucleoside transporters
RT suggests conserved protein structure despite limited sequence
RT identity.";
RL Nucleic Acids Res. 30:4339-4350(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ARG-453 AND
RP 453-ARG--VAL-456.
RX PubMed=12527552;
RA Mangravite L.M., Xiao G., Giacomini K.M.;
RT "Localization of human equilibrative nucleoside transporters, hENT1
RT and hENT2, in renal epithelial cells.";
RL Am. J. Physiol. 284:F902-F910(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-48, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [11]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-293 AND VAL-455.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Mediates both influx and efflux of nucleosides across
CC the membrane (equilibrative transporter). It is sensitive (ES) to
CC low concentrations of the inhibitor nitrobenzylmercaptopurine
CC riboside (NBMPR) and is sodium-independent. It has a higher
CC affinity for adenosine. Inhibited by dipyridamole and dilazep
CC (anticancer chemotherapeutics drugs).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.62 mM for adenosine;
CC Note=Vmax for adenosine uptake is about the same for SLC29A1 and
CC SLC29A2;
CC -!- INTERACTION:
CC P49842:STK19; NbExp=1; IntAct=EBI-347907, EBI-347581;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane; Multi-pass
CC membrane protein. Apical cell membrane; Multi-pass membrane
CC protein. Note=Predominantly localized in the basolateral membrane
CC in polarized MDCK cells.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, mammary gland,
CC erythrocytes and placenta, and also in fetal liver and spleen.
CC -!- PTM: Glycosylated.
CC -!- SIMILARITY: Belongs to the SLC29A/ENT transporter (TC 2.A.57)
CC family.
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DR EMBL; U81375; AAC51103.1; -; mRNA.
DR EMBL; AF190884; AAF02777.1; -; Genomic_DNA.
DR EMBL; AF079117; AAC62495.1; -; mRNA.
DR EMBL; AF495730; AAM11785.1; -; Genomic_DNA.
DR EMBL; AK090615; BAG52197.1; -; mRNA.
DR EMBL; AL139392; CAI20093.1; -; Genomic_DNA.
DR EMBL; BC001382; AAH01382.1; -; mRNA.
DR EMBL; BC008954; AAH08954.1; -; mRNA.
DR RefSeq; NP_001071642.1; NM_001078174.1.
DR RefSeq; NP_001071643.1; NM_001078175.2.
DR RefSeq; NP_001071644.1; NM_001078176.2.
DR RefSeq; NP_001071645.1; NM_001078177.1.
DR RefSeq; NP_004946.1; NM_004955.2.
DR RefSeq; XP_005248935.1; XM_005248878.1.
DR RefSeq; XP_005248936.1; XM_005248879.1.
DR RefSeq; XP_005248937.1; XM_005248880.1.
DR RefSeq; XP_005248938.1; XM_005248881.1.
DR RefSeq; XP_005248939.1; XM_005248882.1.
DR UniGene; Hs.25450; -.
DR ProteinModelPortal; Q99808; -.
DR IntAct; Q99808; 3.
DR MINT; MINT-1034227; -.
DR STRING; 9606.ENSP00000360773; -.
DR BindingDB; Q99808; -.
DR ChEMBL; CHEMBL1997; -.
DR DrugBank; DB00197; Troglitazone.
DR GuidetoPHARMACOLOGY; 1117; -.
DR TCDB; 2.A.57.1.1; the equilibrative nucleoside transporter (ent) family.
DR PhosphoSite; Q99808; -.
DR DMDM; 9296956; -.
DR PaxDb; Q99808; -.
DR PRIDE; Q99808; -.
DR DNASU; 2030; -.
DR Ensembl; ENST00000371708; ENSP00000360773; ENSG00000112759.
DR Ensembl; ENST00000371713; ENSP00000360778; ENSG00000112759.
DR Ensembl; ENST00000371724; ENSP00000360789; ENSG00000112759.
DR Ensembl; ENST00000371731; ENSP00000360796; ENSG00000112759.
DR Ensembl; ENST00000371740; ENSP00000360805; ENSG00000112759.
DR Ensembl; ENST00000371755; ENSP00000360820; ENSG00000112759.
DR Ensembl; ENST00000393841; ENSP00000377424; ENSG00000112759.
DR Ensembl; ENST00000393844; ENSP00000377427; ENSG00000112759.
DR Ensembl; ENST00000427851; ENSP00000392668; ENSG00000112759.
DR GeneID; 2030; -.
DR KEGG; hsa:2030; -.
DR UCSC; uc003owu.1; human.
DR CTD; 2030; -.
DR GeneCards; GC06P044187; -.
DR HGNC; HGNC:11003; SLC29A1.
DR HPA; HPA012383; -.
DR HPA; HPA012384; -.
DR MIM; 602193; gene.
DR neXtProt; NX_Q99808; -.
DR PharmGKB; PA154; -.
DR eggNOG; NOG249415; -.
DR HOGENOM; HOG000007684; -.
DR HOVERGEN; HBG074626; -.
DR InParanoid; Q99808; -.
DR KO; K15014; -.
DR OrthoDB; EOG7PP56W; -.
DR PhylomeDB; Q99808; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; Equilibrative_nucleoside_transporter_1; -.
DR GenomeRNAi; 2030; -.
DR NextBio; 8235; -.
DR PRO; PR:Q99808; -.
DR ArrayExpress; Q99808; -.
DR Bgee; Q99808; -.
DR CleanEx; HS_SLC29A1; -.
DR Genevestigator; Q99808; -.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0015858; P:nucleoside transport; IDA:UniProtKB.
DR GO; GO:0060079; P:regulation of excitatory postsynaptic membrane potential; IEA:Ensembl.
DR GO; GO:0030431; P:sleep; IEA:Ensembl.
DR GO; GO:0015862; P:uridine transport; IEA:Ensembl.
DR InterPro; IPR002259; Eqnu_transpt.
DR InterPro; IPR016196; MFS_dom_general_subst_transpt.
DR PANTHER; PTHR10332; PTHR10332; 1.
DR Pfam; PF01733; Nucleoside_tran; 1.
DR PIRSF; PIRSF016379; ENT; 1.
DR PRINTS; PR01130; DERENTRNSPRT.
DR SUPFAM; SSF103473; SSF103473; 3.
DR TIGRFAMs; TIGR00939; 2a57; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Direct protein sequencing;
KW Glycoprotein; Membrane; Polymorphism; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 456 Equilibrative nucleoside transporter 1.
FT /FTId=PRO_0000209337.
FT TOPO_DOM 2 12 Cytoplasmic (Potential).
FT TRANSMEM 13 29 Helical; (Potential).
FT TOPO_DOM 30 82 Extracellular (Potential).
FT TRANSMEM 83 107 Helical; (Potential).
FT TOPO_DOM 108 111 Cytoplasmic (Potential).
FT TRANSMEM 112 130 Helical; (Potential).
FT TOPO_DOM 131 138 Extracellular (Potential).
FT TRANSMEM 139 157 Helical; (Potential).
FT TOPO_DOM 158 174 Cytoplasmic (Potential).
FT TRANSMEM 175 199 Helical; (Potential).
FT TOPO_DOM 200 206 Extracellular (Potential).
FT TRANSMEM 207 227 Helical; (Potential).
FT TOPO_DOM 228 291 Cytoplasmic (Potential).
FT TRANSMEM 292 311 Helical; (Potential).
FT TOPO_DOM 312 323 Extracellular (Potential).
FT TRANSMEM 324 342 Helical; (Potential).
FT TOPO_DOM 343 359 Cytoplasmic (Potential).
FT TRANSMEM 360 378 Helical; (Potential).
FT TOPO_DOM 379 393 Extracellular (Potential).
FT TRANSMEM 394 413 Helical; (Potential).
FT TOPO_DOM 414 431 Cytoplasmic (Potential).
FT TRANSMEM 432 452 Helical; (Potential).
FT TOPO_DOM 453 456 Extracellular (Potential).
FT CARBOHYD 48 48 N-linked (GlcNAc...).
FT VARIANT 216 216 I -> T (in dbSNP:rs45573936).
FT /FTId=VAR_053668.
FT VARIANT 293 293 A -> T (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036221.
FT VARIANT 391 391 E -> K (in dbSNP:rs45458701).
FT /FTId=VAR_053669.
FT VARIANT 455 455 I -> V (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036222.
FT MUTAGEN 453 456 Missing: No effect on subcellular
FT localization and inosine transport.
FT MUTAGEN 453 453 R->A: No effect on subcellular
FT localization and inosine transport.
SQ SEQUENCE 456 AA; 50219 MW; F18535A95DEBC95D CRC64;
MTTSHQPQDR YKAVWLIFFM LGLGTLLPWN FFMTATQYFT NRLDMSQNVS LVTAELSKDA
QASAAPAAPL PERNSLSAIF NNVMTLCAML PLLLFTYLNS FLHQRIPQSV RILGSLVAIL
LVFLITAILV KVQLDALPFF VITMIKIVLI NSFGAILQGS LFGLAGLLPA SYTAPIMSGQ
GLAGFFASVA MICAIASGSE LSESAFGYFI TACAVIILTI ICYLGLPRLE FYRYYQQLKL
EGPGEQETKL DLISKGEEPR AGKEESGVSV SNSQPTNESH SIKAILKNIS VLAFSVCFIF
TITIGMFPAV TVEVKSSIAG SSTWERYFIP VSCFLTFNIF DWLGRSLTAV FMWPGKDSRW
LPSLVLARLV FVPLLLLCNI KPRRYLTVVF EHDAWFIFFM AAFAFSNGYL ASLCMCFGPK
KVKPAEAETA GAIMAFFLCL GLALGAVFSF LFRAIV
//
ID S29A1_HUMAN Reviewed; 456 AA.
AC Q99808; B3KQY5; Q5T9W9; Q9UJY2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Equilibrative nucleoside transporter 1;
DE AltName: Full=Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter;
DE Short=Equilibrative NBMPR-sensitive nucleoside transporter;
DE AltName: Full=Nucleoside transporter, es-type;
DE AltName: Full=Solute carrier family 29 member 1;
GN Name=SLC29A1; Synonyms=ENT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-22.
RC TISSUE=Placenta;
RX PubMed=8986748; DOI=10.1038/nm0197-89;
RA Griffiths M., Beaumont N., Yao S.Y.M., Sundaram M., Boumah C.E.,
RA Davies A., Kwong F.Y.P., Coe I., Cass C.E., Young J.D., Baldwin S.A.;
RT "Cloning of a human nucleoside transporter implicated in the cellular
RT uptake of adenosine and chemotherapeutic drugs.";
RL Nat. Med. 3:89-93(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Graham K.A., Coe I.R., Carpenter P., Baldwin S.A., Young J.D.,
RA Cass C.E.;
RT "Genomic sequence of the human equilibrative nucleoside transporter 1
RT (hENT1).";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Jejunum, and Small intestine;
RX PubMed=10755314; DOI=10.1007/s002800050040;
RA Lum P.Y., Ngo L.Y., Bakken A.H., Unadkat J.D.;
RT "Human intestinal es nucleoside transporter: molecular
RT characterization and nucleoside inhibitory profiles.";
RL Cancer Chemother. Pharmacol. 45:273-278(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12384580; DOI=10.1093/nar/gkf564;
RA Sankar N., Machado J., Abdulla P., Hilliker A.J., Coe I.R.;
RT "Comparative genomic analysis of equilibrative nucleoside transporters
RT suggests conserved protein structure despite limited sequence
RT identity.";
RL Nucleic Acids Res. 30:4339-4350(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ARG-453 AND
RP 453-ARG--VAL-456.
RX PubMed=12527552;
RA Mangravite L.M., Xiao G., Giacomini K.M.;
RT "Localization of human equilibrative nucleoside transporters, hENT1
RT and hENT2, in renal epithelial cells.";
RL Am. J. Physiol. 284:F902-F910(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-48, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [11]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-293 AND VAL-455.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Mediates both influx and efflux of nucleosides across
CC the membrane (equilibrative transporter). It is sensitive (ES) to
CC low concentrations of the inhibitor nitrobenzylmercaptopurine
CC riboside (NBMPR) and is sodium-independent. It has a higher
CC affinity for adenosine. Inhibited by dipyridamole and dilazep
CC (anticancer chemotherapeutics drugs).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.62 mM for adenosine;
CC Note=Vmax for adenosine uptake is about the same for SLC29A1 and
CC SLC29A2;
CC -!- INTERACTION:
CC P49842:STK19; NbExp=1; IntAct=EBI-347907, EBI-347581;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane; Multi-pass
CC membrane protein. Apical cell membrane; Multi-pass membrane
CC protein. Note=Predominantly localized in the basolateral membrane
CC in polarized MDCK cells.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, mammary gland,
CC erythrocytes and placenta, and also in fetal liver and spleen.
CC -!- PTM: Glycosylated.
CC -!- SIMILARITY: Belongs to the SLC29A/ENT transporter (TC 2.A.57)
CC family.
CC -----------------------------------------------------------------------
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DR EMBL; U81375; AAC51103.1; -; mRNA.
DR EMBL; AF190884; AAF02777.1; -; Genomic_DNA.
DR EMBL; AF079117; AAC62495.1; -; mRNA.
DR EMBL; AF495730; AAM11785.1; -; Genomic_DNA.
DR EMBL; AK090615; BAG52197.1; -; mRNA.
DR EMBL; AL139392; CAI20093.1; -; Genomic_DNA.
DR EMBL; BC001382; AAH01382.1; -; mRNA.
DR EMBL; BC008954; AAH08954.1; -; mRNA.
DR RefSeq; NP_001071642.1; NM_001078174.1.
DR RefSeq; NP_001071643.1; NM_001078175.2.
DR RefSeq; NP_001071644.1; NM_001078176.2.
DR RefSeq; NP_001071645.1; NM_001078177.1.
DR RefSeq; NP_004946.1; NM_004955.2.
DR RefSeq; XP_005248935.1; XM_005248878.1.
DR RefSeq; XP_005248936.1; XM_005248879.1.
DR RefSeq; XP_005248937.1; XM_005248880.1.
DR RefSeq; XP_005248938.1; XM_005248881.1.
DR RefSeq; XP_005248939.1; XM_005248882.1.
DR UniGene; Hs.25450; -.
DR ProteinModelPortal; Q99808; -.
DR IntAct; Q99808; 3.
DR MINT; MINT-1034227; -.
DR STRING; 9606.ENSP00000360773; -.
DR BindingDB; Q99808; -.
DR ChEMBL; CHEMBL1997; -.
DR DrugBank; DB00197; Troglitazone.
DR GuidetoPHARMACOLOGY; 1117; -.
DR TCDB; 2.A.57.1.1; the equilibrative nucleoside transporter (ent) family.
DR PhosphoSite; Q99808; -.
DR DMDM; 9296956; -.
DR PaxDb; Q99808; -.
DR PRIDE; Q99808; -.
DR DNASU; 2030; -.
DR Ensembl; ENST00000371708; ENSP00000360773; ENSG00000112759.
DR Ensembl; ENST00000371713; ENSP00000360778; ENSG00000112759.
DR Ensembl; ENST00000371724; ENSP00000360789; ENSG00000112759.
DR Ensembl; ENST00000371731; ENSP00000360796; ENSG00000112759.
DR Ensembl; ENST00000371740; ENSP00000360805; ENSG00000112759.
DR Ensembl; ENST00000371755; ENSP00000360820; ENSG00000112759.
DR Ensembl; ENST00000393841; ENSP00000377424; ENSG00000112759.
DR Ensembl; ENST00000393844; ENSP00000377427; ENSG00000112759.
DR Ensembl; ENST00000427851; ENSP00000392668; ENSG00000112759.
DR GeneID; 2030; -.
DR KEGG; hsa:2030; -.
DR UCSC; uc003owu.1; human.
DR CTD; 2030; -.
DR GeneCards; GC06P044187; -.
DR HGNC; HGNC:11003; SLC29A1.
DR HPA; HPA012383; -.
DR HPA; HPA012384; -.
DR MIM; 602193; gene.
DR neXtProt; NX_Q99808; -.
DR PharmGKB; PA154; -.
DR eggNOG; NOG249415; -.
DR HOGENOM; HOG000007684; -.
DR HOVERGEN; HBG074626; -.
DR InParanoid; Q99808; -.
DR KO; K15014; -.
DR OrthoDB; EOG7PP56W; -.
DR PhylomeDB; Q99808; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; Equilibrative_nucleoside_transporter_1; -.
DR GenomeRNAi; 2030; -.
DR NextBio; 8235; -.
DR PRO; PR:Q99808; -.
DR ArrayExpress; Q99808; -.
DR Bgee; Q99808; -.
DR CleanEx; HS_SLC29A1; -.
DR Genevestigator; Q99808; -.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0015858; P:nucleoside transport; IDA:UniProtKB.
DR GO; GO:0060079; P:regulation of excitatory postsynaptic membrane potential; IEA:Ensembl.
DR GO; GO:0030431; P:sleep; IEA:Ensembl.
DR GO; GO:0015862; P:uridine transport; IEA:Ensembl.
DR InterPro; IPR002259; Eqnu_transpt.
DR InterPro; IPR016196; MFS_dom_general_subst_transpt.
DR PANTHER; PTHR10332; PTHR10332; 1.
DR Pfam; PF01733; Nucleoside_tran; 1.
DR PIRSF; PIRSF016379; ENT; 1.
DR PRINTS; PR01130; DERENTRNSPRT.
DR SUPFAM; SSF103473; SSF103473; 3.
DR TIGRFAMs; TIGR00939; 2a57; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Direct protein sequencing;
KW Glycoprotein; Membrane; Polymorphism; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 456 Equilibrative nucleoside transporter 1.
FT /FTId=PRO_0000209337.
FT TOPO_DOM 2 12 Cytoplasmic (Potential).
FT TRANSMEM 13 29 Helical; (Potential).
FT TOPO_DOM 30 82 Extracellular (Potential).
FT TRANSMEM 83 107 Helical; (Potential).
FT TOPO_DOM 108 111 Cytoplasmic (Potential).
FT TRANSMEM 112 130 Helical; (Potential).
FT TOPO_DOM 131 138 Extracellular (Potential).
FT TRANSMEM 139 157 Helical; (Potential).
FT TOPO_DOM 158 174 Cytoplasmic (Potential).
FT TRANSMEM 175 199 Helical; (Potential).
FT TOPO_DOM 200 206 Extracellular (Potential).
FT TRANSMEM 207 227 Helical; (Potential).
FT TOPO_DOM 228 291 Cytoplasmic (Potential).
FT TRANSMEM 292 311 Helical; (Potential).
FT TOPO_DOM 312 323 Extracellular (Potential).
FT TRANSMEM 324 342 Helical; (Potential).
FT TOPO_DOM 343 359 Cytoplasmic (Potential).
FT TRANSMEM 360 378 Helical; (Potential).
FT TOPO_DOM 379 393 Extracellular (Potential).
FT TRANSMEM 394 413 Helical; (Potential).
FT TOPO_DOM 414 431 Cytoplasmic (Potential).
FT TRANSMEM 432 452 Helical; (Potential).
FT TOPO_DOM 453 456 Extracellular (Potential).
FT CARBOHYD 48 48 N-linked (GlcNAc...).
FT VARIANT 216 216 I -> T (in dbSNP:rs45573936).
FT /FTId=VAR_053668.
FT VARIANT 293 293 A -> T (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036221.
FT VARIANT 391 391 E -> K (in dbSNP:rs45458701).
FT /FTId=VAR_053669.
FT VARIANT 455 455 I -> V (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036222.
FT MUTAGEN 453 456 Missing: No effect on subcellular
FT localization and inosine transport.
FT MUTAGEN 453 453 R->A: No effect on subcellular
FT localization and inosine transport.
SQ SEQUENCE 456 AA; 50219 MW; F18535A95DEBC95D CRC64;
MTTSHQPQDR YKAVWLIFFM LGLGTLLPWN FFMTATQYFT NRLDMSQNVS LVTAELSKDA
QASAAPAAPL PERNSLSAIF NNVMTLCAML PLLLFTYLNS FLHQRIPQSV RILGSLVAIL
LVFLITAILV KVQLDALPFF VITMIKIVLI NSFGAILQGS LFGLAGLLPA SYTAPIMSGQ
GLAGFFASVA MICAIASGSE LSESAFGYFI TACAVIILTI ICYLGLPRLE FYRYYQQLKL
EGPGEQETKL DLISKGEEPR AGKEESGVSV SNSQPTNESH SIKAILKNIS VLAFSVCFIF
TITIGMFPAV TVEVKSSIAG SSTWERYFIP VSCFLTFNIF DWLGRSLTAV FMWPGKDSRW
LPSLVLARLV FVPLLLLCNI KPRRYLTVVF EHDAWFIFFM AAFAFSNGYL ASLCMCFGPK
KVKPAEAETA GAIMAFFLCL GLALGAVFSF LFRAIV
//
MIM
602193
*RECORD*
*FIELD* NO
602193
*FIELD* TI
*602193 SOLUTE CARRIER FAMILY 29 (NUCLEOSIDE TRANSPORTER), MEMBER 1; SLC29A1
;;EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; ENT1
read more*FIELD* TX
DESCRIPTION
The uptake of nucleosides by transporters, such as SLC29A1, is essential
for nucleotide synthesis by salvage pathways in cells that lack de novo
biosynthetic pathways. Nucleoside transport also plays a key role in the
regulation of many physiologic processes through its effect on adenosine
concentration at the cell surface. There are 2 major families of
nucleoside transporters, the concentrative and the equilibrative.
Concentrative nucleoside transporters appear to be restricted in their
distribution within cells and tissues and also in their selectivity of
nucleoside permeants. In contrast, equilibrative nucleoside transporters
appear to be widely distributed and have a broad substrate specificity.
SLC29A1 is an equilibrative nucleoside transporter (Griffiths et al.,
1997).
CLONING
Griffiths et al. (1997) cloned the cDNA for the prototypic equilibrative
transporter SLC29A1, which they called ENT1, from human placenta. The
deduced 456-amino acid glycoprotein has 11 predicted transmembrane
domains.
Choi et al. (2000) cloned and sequenced the mouse Ent1 gene. Northern
blot analysis detected expression of Ent1 in all tissues except skeletal
muscle, with highest levels in liver, heart, testis, spleen, lung,
kidney, and brain.
GENE FUNCTION
Griffiths et al. (1997) found that both ENT1 and ENT2 (SLC29A2; 602110)
showed saturable sodium-independent equilibrative transport of adenosine
and uridine following expression in Xenopus oocytes. ENT1 was more
efficient than ENT2 in transport of both substrates, and ENT1, but not
ENT2, was sensitive to inhibition by nitrobenzylmercaptopurine riboside
(NBMPR).
Ward et al. (2000) found that human ENT1 showed higher affinity than
ENT2 for transport of thymidine, adenosine, cytidine, and guanosine
following expression in porcine kidney cells. However, ENT2 showed
4-fold higher affinity than ENT1 for inosine. The nucleobase
hypoxanthine inhibited uridine uptake by ENT2, but had minimal effect on
ENT1.
Yao et al. (2001) expressed rat and human ENT1 and ENT2 in Xenopus
oocytes and characterized their ability to transport three
3-prime-deoxy-nucleoside analogs used in human immunodeficiency virus
(HIV) therapy: 2-prime,3-prime-dideoxycytidine (ddC),
3-prime-azido-3-prime-deoxythymidine (AZT), and
2-prime,3-prime-dideoxyinosine (ddI). Rat and human ENT2 transported
ddC, AZT, and ddI, whereas rat and human ENT1 transported ddC and ddI
only. Relative to uridine, ENT2 mediated substantially larger fluxes of
ddC and ddI compared with ENT1. Fusion of the N-terminal half of rat
Ent2 with rat Ent1 allowed Ent1 to transport AZT and enhanced its uptake
of ddC and ddI, indicating that the N-terminal region of ENT proteins is
the major site of 3-prime-deoxy-nucleoside interaction.
SenGupta et al. (2002) found that mutation of gly179 in transmembrane
domain 5 of human ENT1 to leu, cys, or val abolished transport of
nucleoside analogs in a yeast nucleoside transporter assay. These
mutations had no effect on targeting of the transporter to the plasma
membrane. More conservative mutations, such as gly179 to ala or ser,
preserved both targeting and transport activity of ENT1 in yeast,
although the gly179-to-ala mutation was associated with reduced uridine
transport compared with wildtype ENT1 and a small but significantly
reduced sensitivity to NBMPR. Point mutations at gly184 resulted in poor
targeting of ENT1 to the plasma membrane and, consequently, little or no
transport activity.
MAPPING
By fluorescence in situ hybridization, Coe et al. (1997) mapped the ENT1
gene to chromosome 6p21.2-p21.1. By in situ hybridization, Choi et al.
(2000) mapped the mouse Ent1 gene to chromosome 17C.
ANIMAL MODEL
Adenosine is an important mediator of ethanol intoxication and exerts
some of its effects via the adenosine A1 receptor (ADORA1; 102775) in
the central nervous system. In vitro, acute ethanol exposure increases
extracellular adenosine levels by inhibiting ENT1; chronic ethanol
exposure results in a decrease of ENT1 expression (Nagy et al., 1990).
Choi et al. (2004) found that Ent1-null mice showed reduced hypnotic and
ataxic responses to ethanol and increased voluntary ethanol
self-administration compared to wildtype littermates. These features
were associated with a decrease in the activation of A1 receptors in the
nucleus accumbens. Treatment with an A1 receptor agonist reduced ethanol
consumption in the Ent1-null mice. These findings supported a role for
ENT1 in ethanol-mediated behaviors and suggested that decreased A1
receptor function promotes alcohol consumption.
*FIELD* RF
1. Choi, D.-S.; Cascini, M.-G.; Mailliard, W.; Young, H.; Paredes,
P.; McMahon, T.; Diamond, I.; Bonci, A.; Messing, R. O.: The type
1 equilibrative nucleoside transporter regulates ethanol intoxication
and preference. Nature Neurosci. 7: 855-861, 2004.
2. Choi, D.-S.; Handa, M.; Young, H.; Gordon, A. S.; Diamond, I.;
Messing, R. O.: Genomic organization and expression of the mouse
equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporter
1 (ENT1) gene. Biochem. Biophys. Res. Commun. 277: 200-208, 2000.
3. Coe, I. R.; Griffiths, M.; Young, J. D.; Baldwin, S. A.; Cass,
C. E.: Assignment of the human equilibrative nucleoside transporter
(hENT1) to 6p21.1-p21.2. Genomics 45: 459-460, 1997.
4. Griffiths, M.; Beaumont, N.; Yao, S. Y. M.; Sundaram, M.; Boumah,
C. E.; Davies, A.; Kwong, F. Y. P.; Coe, I.; Cass, C. E.; Young, J.
D.; Baldwin, S. A.: Cloning of a human nucleoside transporter implicated
in the cellular uptake of adenosine and chemotherapeutic drugs. Nature
Med. 3: 89-94, 1997.
5. Griffiths, M.; Yao, S. Y. M.; Abidi, F.; Phillips, S. E. V.; Cass,
C. E.; Young, J. D.; Baldwin, S. A.: Molecular cloning and characterization
of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside
transporter from human placenta. Biochem. J. 328: 739-743, 1997.
6. Nagy, L. E.; Diamond, I.; Casso, D. J.; Franklin, C.; Gordon, A.
S.: Ethanol increases extracellular adenosine by inhibiting adenosine
uptake via the nucleoside transporter. J. Biol. Chem. 265: 1946-1951,
1990.
7. SenGupta, D. J.; Lum, P. Y.; Lai, Y.; Shubochkina, E.; Bakken,
A. H.; Schneider, G.; Unadkat, J. D.: A single glycine mutation in
the equilibrative nucleoside transporter gene, hENT1, alters nucleoside
transport activity and sensitivity to nitrobenzylthioinosine. Biochemistry 41:
1512-1519, 2002.
8. Ward, J. L.; Sherali, A.; Mo., Z.-P.; Tse, C.-M.: Kinetic and
pharmacological properties of cloned human equilibrative nucleoside
transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient
PK15 cells: ENT2 exhibits a low affinity for guanosine and cytidine
but a high affinity for inosine. J. Biol. Chem. 275: 8375-8381,
2000.
9. Yao, S. Y. M.; Ng, A. M. L.; Sundaram, M.; Cass, C. E.; Baldwin,
S. A.; Young, J. D.: Transport of antiviral 3-prime-deoxy-nucleoside
drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine
(NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced
in Xenopus oocytes. Molec. Membrane Biol. 18: 161-167, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 11/7/2008
Cassandra L. Kniffin - updated: 7/23/2004
Carol A. Bocchini - updated: 6/18/2002
*FIELD* CD
Victor A. McKusick: 12/16/1997
*FIELD* ED
mgross: 11/11/2008
terry: 11/7/2008
terry: 4/5/2005
alopez: 8/30/2004
tkritzer: 7/26/2004
ckniffin: 7/23/2004
terry: 6/19/2002
carol: 6/18/2002
carol: 3/8/2002
terry: 3/8/2002
psherman: 7/29/1999
dholmes: 12/31/1997
mark: 12/16/1997
*RECORD*
*FIELD* NO
602193
*FIELD* TI
*602193 SOLUTE CARRIER FAMILY 29 (NUCLEOSIDE TRANSPORTER), MEMBER 1; SLC29A1
;;EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; ENT1
read more*FIELD* TX
DESCRIPTION
The uptake of nucleosides by transporters, such as SLC29A1, is essential
for nucleotide synthesis by salvage pathways in cells that lack de novo
biosynthetic pathways. Nucleoside transport also plays a key role in the
regulation of many physiologic processes through its effect on adenosine
concentration at the cell surface. There are 2 major families of
nucleoside transporters, the concentrative and the equilibrative.
Concentrative nucleoside transporters appear to be restricted in their
distribution within cells and tissues and also in their selectivity of
nucleoside permeants. In contrast, equilibrative nucleoside transporters
appear to be widely distributed and have a broad substrate specificity.
SLC29A1 is an equilibrative nucleoside transporter (Griffiths et al.,
1997).
CLONING
Griffiths et al. (1997) cloned the cDNA for the prototypic equilibrative
transporter SLC29A1, which they called ENT1, from human placenta. The
deduced 456-amino acid glycoprotein has 11 predicted transmembrane
domains.
Choi et al. (2000) cloned and sequenced the mouse Ent1 gene. Northern
blot analysis detected expression of Ent1 in all tissues except skeletal
muscle, with highest levels in liver, heart, testis, spleen, lung,
kidney, and brain.
GENE FUNCTION
Griffiths et al. (1997) found that both ENT1 and ENT2 (SLC29A2; 602110)
showed saturable sodium-independent equilibrative transport of adenosine
and uridine following expression in Xenopus oocytes. ENT1 was more
efficient than ENT2 in transport of both substrates, and ENT1, but not
ENT2, was sensitive to inhibition by nitrobenzylmercaptopurine riboside
(NBMPR).
Ward et al. (2000) found that human ENT1 showed higher affinity than
ENT2 for transport of thymidine, adenosine, cytidine, and guanosine
following expression in porcine kidney cells. However, ENT2 showed
4-fold higher affinity than ENT1 for inosine. The nucleobase
hypoxanthine inhibited uridine uptake by ENT2, but had minimal effect on
ENT1.
Yao et al. (2001) expressed rat and human ENT1 and ENT2 in Xenopus
oocytes and characterized their ability to transport three
3-prime-deoxy-nucleoside analogs used in human immunodeficiency virus
(HIV) therapy: 2-prime,3-prime-dideoxycytidine (ddC),
3-prime-azido-3-prime-deoxythymidine (AZT), and
2-prime,3-prime-dideoxyinosine (ddI). Rat and human ENT2 transported
ddC, AZT, and ddI, whereas rat and human ENT1 transported ddC and ddI
only. Relative to uridine, ENT2 mediated substantially larger fluxes of
ddC and ddI compared with ENT1. Fusion of the N-terminal half of rat
Ent2 with rat Ent1 allowed Ent1 to transport AZT and enhanced its uptake
of ddC and ddI, indicating that the N-terminal region of ENT proteins is
the major site of 3-prime-deoxy-nucleoside interaction.
SenGupta et al. (2002) found that mutation of gly179 in transmembrane
domain 5 of human ENT1 to leu, cys, or val abolished transport of
nucleoside analogs in a yeast nucleoside transporter assay. These
mutations had no effect on targeting of the transporter to the plasma
membrane. More conservative mutations, such as gly179 to ala or ser,
preserved both targeting and transport activity of ENT1 in yeast,
although the gly179-to-ala mutation was associated with reduced uridine
transport compared with wildtype ENT1 and a small but significantly
reduced sensitivity to NBMPR. Point mutations at gly184 resulted in poor
targeting of ENT1 to the plasma membrane and, consequently, little or no
transport activity.
MAPPING
By fluorescence in situ hybridization, Coe et al. (1997) mapped the ENT1
gene to chromosome 6p21.2-p21.1. By in situ hybridization, Choi et al.
(2000) mapped the mouse Ent1 gene to chromosome 17C.
ANIMAL MODEL
Adenosine is an important mediator of ethanol intoxication and exerts
some of its effects via the adenosine A1 receptor (ADORA1; 102775) in
the central nervous system. In vitro, acute ethanol exposure increases
extracellular adenosine levels by inhibiting ENT1; chronic ethanol
exposure results in a decrease of ENT1 expression (Nagy et al., 1990).
Choi et al. (2004) found that Ent1-null mice showed reduced hypnotic and
ataxic responses to ethanol and increased voluntary ethanol
self-administration compared to wildtype littermates. These features
were associated with a decrease in the activation of A1 receptors in the
nucleus accumbens. Treatment with an A1 receptor agonist reduced ethanol
consumption in the Ent1-null mice. These findings supported a role for
ENT1 in ethanol-mediated behaviors and suggested that decreased A1
receptor function promotes alcohol consumption.
*FIELD* RF
1. Choi, D.-S.; Cascini, M.-G.; Mailliard, W.; Young, H.; Paredes,
P.; McMahon, T.; Diamond, I.; Bonci, A.; Messing, R. O.: The type
1 equilibrative nucleoside transporter regulates ethanol intoxication
and preference. Nature Neurosci. 7: 855-861, 2004.
2. Choi, D.-S.; Handa, M.; Young, H.; Gordon, A. S.; Diamond, I.;
Messing, R. O.: Genomic organization and expression of the mouse
equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporter
1 (ENT1) gene. Biochem. Biophys. Res. Commun. 277: 200-208, 2000.
3. Coe, I. R.; Griffiths, M.; Young, J. D.; Baldwin, S. A.; Cass,
C. E.: Assignment of the human equilibrative nucleoside transporter
(hENT1) to 6p21.1-p21.2. Genomics 45: 459-460, 1997.
4. Griffiths, M.; Beaumont, N.; Yao, S. Y. M.; Sundaram, M.; Boumah,
C. E.; Davies, A.; Kwong, F. Y. P.; Coe, I.; Cass, C. E.; Young, J.
D.; Baldwin, S. A.: Cloning of a human nucleoside transporter implicated
in the cellular uptake of adenosine and chemotherapeutic drugs. Nature
Med. 3: 89-94, 1997.
5. Griffiths, M.; Yao, S. Y. M.; Abidi, F.; Phillips, S. E. V.; Cass,
C. E.; Young, J. D.; Baldwin, S. A.: Molecular cloning and characterization
of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside
transporter from human placenta. Biochem. J. 328: 739-743, 1997.
6. Nagy, L. E.; Diamond, I.; Casso, D. J.; Franklin, C.; Gordon, A.
S.: Ethanol increases extracellular adenosine by inhibiting adenosine
uptake via the nucleoside transporter. J. Biol. Chem. 265: 1946-1951,
1990.
7. SenGupta, D. J.; Lum, P. Y.; Lai, Y.; Shubochkina, E.; Bakken,
A. H.; Schneider, G.; Unadkat, J. D.: A single glycine mutation in
the equilibrative nucleoside transporter gene, hENT1, alters nucleoside
transport activity and sensitivity to nitrobenzylthioinosine. Biochemistry 41:
1512-1519, 2002.
8. Ward, J. L.; Sherali, A.; Mo., Z.-P.; Tse, C.-M.: Kinetic and
pharmacological properties of cloned human equilibrative nucleoside
transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient
PK15 cells: ENT2 exhibits a low affinity for guanosine and cytidine
but a high affinity for inosine. J. Biol. Chem. 275: 8375-8381,
2000.
9. Yao, S. Y. M.; Ng, A. M. L.; Sundaram, M.; Cass, C. E.; Baldwin,
S. A.; Young, J. D.: Transport of antiviral 3-prime-deoxy-nucleoside
drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine
(NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced
in Xenopus oocytes. Molec. Membrane Biol. 18: 161-167, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 11/7/2008
Cassandra L. Kniffin - updated: 7/23/2004
Carol A. Bocchini - updated: 6/18/2002
*FIELD* CD
Victor A. McKusick: 12/16/1997
*FIELD* ED
mgross: 11/11/2008
terry: 11/7/2008
terry: 4/5/2005
alopez: 8/30/2004
tkritzer: 7/26/2004
ckniffin: 7/23/2004
terry: 6/19/2002
carol: 6/18/2002
carol: 3/8/2002
terry: 3/8/2002
psherman: 7/29/1999
dholmes: 12/31/1997
mark: 12/16/1997