ID S29A2_HUMAN Reviewed; 456 AA. AC Q14542; B3KPY7; G5E943; O43530; Q52M84; Q96R00; Q9UPE0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 24-JAN-2024, entry version 193. DE RecName: Full=Equilibrative nucleoside transporter 2 {ECO:0000303|PubMed:9396714}; DE Short=hENT2 {ECO:0000303|PubMed:9396714}; DE AltName: Full=36 kDa nucleolar protein HNP36 {ECO:0000303|PubMed:7639753}; DE AltName: Full=Delayed-early response protein 12 {ECO:0000303|PubMed:7639753}; DE AltName: Full=Equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter {ECO:0000303|PubMed:9478986}; DE Short=Equilibrative NBMPR-insensitive nucleoside transporter {ECO:0000303|PubMed:9478986}; DE AltName: Full=Hydrophobic nucleolar protein, 36 kDa; DE AltName: Full=Nucleoside transporter, ei-type {ECO:0000303|PubMed:7639753}; DE AltName: Full=Solute carrier family 29 member 2 {ECO:0000303|PubMed:23639800}; GN Name=SLC29A2 {ECO:0000312|HGNC:HGNC:11004}; GN Synonyms=DER12, ENT2, HNP36; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Heart; RX PubMed=7639753; DOI=10.1006/bbrc.1995.2133; RA Williams J.B., Lanahan A.A.; RT "A mammalian delayed-early response gene encodes HNP36, a novel, conserved RT nucleolar protein."; RL Biochem. Biophys. Res. Commun. 213:325-333(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND MISCELLANEOUS. RC TISSUE=Placenta; RX PubMed=9396714; DOI=10.1042/bj3280739; RA Griffiths M., Yao S.Y., Abidi F., Phillips S.E., Cass C.E., Young J.D., RA Baldwin S.A.; RT "Molecular cloning and characterization of a nitrobenzylthioinosine- RT insensitive (ei) equilibrative nucleoside transporter from human RT placenta."; RL Biochem. J. 328:739-743(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY, RP TISSUE SPECIFICITY, AND MISCELLANEOUS. RX PubMed=9478986; DOI=10.1074/jbc.273.9.5288; RA Crawford C.R., Patel D.H., Naeve C., Belt J.A.; RT "Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside RT (NBMPR)-insensitive nucleoside transporter ei by functional expression in a RT transport-deficient cell line."; RL J. Biol. Chem. 273:5288-5293(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TRANSPORTER ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LEU-455 AND LEU-456. RX PubMed=12527552; DOI=10.1152/ajprenal.00215.2002; RA Mangravite L.M., Xiao G., Giacomini K.M.; RT "Localization of human equilibrative nucleoside transporters, hENT1 and RT hENT2, in renal epithelial cells."; RL Am. J. Physiol. 284:F902-F910(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; 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 [9] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP GLYCOSYLATION, AND MISCELLANEOUS. RX PubMed=10722669; DOI=10.1074/jbc.275.12.8375; RA Ward J.L., Sherali A., Mo Z.P., Tse C.M.; RT "Kinetic and pharmacological properties of cloned human equilibrative RT nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside RT transporter-deficient PK15 cells. Ent2 exhibits a low affinity for RT guanosine and cytidine but a high affinity for inosine."; RL J. Biol. Chem. 275:8375-8381(2000). RN [10] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP GLYCOSYLATION AT ASN-48 AND ASN-57, MUTAGENESIS OF ASN-48 AND ASN-57, AND RP MISCELLANEOUS. RX PubMed=12590919; DOI=10.1016/s0003-9861(02)00718-x; RA Ward J.L., Leung G.P., Toan S.V., Tse C.-M.; RT "Functional analysis of site-directed glycosylation mutants of the human RT equilibrative nucleoside transporter-2."; RL Arch. Biochem. Biophys. 411:19-26(2003). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MISCELLANEOUS. RX PubMed=21795683; DOI=10.1074/jbc.m111.236117; RA Yao S.Y., Ng A.M., Cass C.E., Baldwin S.A., Young J.D.; RT "Nucleobase transport by human equilibrative nucleoside transporter 1 RT (hENT1)."; RL J. Biol. Chem. 286:32552-32562(2011). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=23639800; DOI=10.1124/jpet.113.203265; RA Klein D.M., Evans K.K., Hardwick R.N., Dantzler W.H., Wright S.H., RA Cherrington N.J.; RT "Basolateral uptake of nucleosides by Sertoli cells is mediated primarily RT by equilibrative nucleoside transporter 1."; RL J. Pharmacol. Exp. Ther. 346:121-129(2013). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP CAUTION. RX PubMed=27271752; DOI=10.1007/s00018-016-2288-9; RA Grane-Boladeras N., Spring C.M., Hanna W.J., Pastor-Anglada M., Coe I.R.; RT "Novel nuclear hENT2 isoforms regulate cell cycle progression via RT controlling nucleoside transport and nuclear reservoir."; RL Cell. Mol. Life Sci. 73:4559-4575(2016). RN [18] RP FUNCTION, TRANSPORTER ACTIVITY, VARIANTS TYR-5; LYS-68; LEU-94 AND RP 184-SER--VAL-186 DELINS MET, AND CHARACTERIZATION OF VARIANTS TYR-5; RP LYS-68; LEU-94 AND 184-SER--VAL-186 DELINS MET. RX PubMed=16214850; DOI=10.1124/dmd.105.006270; RA Owen R.P., Lagpacan L.L., Taylor T.R., De La Cruz M., Huang C.C., RA Kawamoto M., Johns S.J., Stryke D., Ferrin T.E., Giacomini K.M.; RT "Functional characterization and haplotype analysis of polymorphisms in the RT human equilibrative nucleoside transporter, ENT2."; RL Drug Metab. Dispos. 34:12-15(2006). CC -!- FUNCTION: Bidirectional uniporter involved in the facilitative CC transport of nucleosides and nucleobases, and contributes to CC maintaining their cellular homeostasis (PubMed:9396714, PubMed:9478986, CC PubMed:12527552, PubMed:10722669, PubMed:12590919, PubMed:21795683, CC PubMed:16214850). Functions as a Na(+)-independent, passive transporter CC (PubMed:9478986). Involved in the transport of nucleosides such as CC inosine, adenosine, uridine, thymidine, cytidine and guanosine CC (PubMed:9396714, PubMed:9478986, PubMed:12527552, PubMed:10722669, CC PubMed:12590919, PubMed:21795683, PubMed:16214850). Also able to CC transport purine nucleobases (hypoxanthine, adenine, guanine) and CC pyrimidine nucleobases (thymine, uracil) (PubMed:21795683, CC PubMed:16214850). Involved in nucleoside transport at basolateral CC membrane of kidney cells, allowing liver absorption of nucleoside CC metabolites (PubMed:12527552). Mediates apical nucleoside uptake into CC Sertoli cells, thereby regulating the transport of nucleosides in CC testis across the blood-testis-barrier (PubMed:23639800). Mediates both CC the influx and efflux of hypoxanthine in skeletal muscle microvascular CC endothelial cells to control the amount of intracellular hypoxanthine CC available for xanthine oxidase-mediated ROS production (By similarity). CC {ECO:0000250|UniProtKB:O54699, ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12527552, ECO:0000269|PubMed:12590919, CC ECO:0000269|PubMed:16214850, ECO:0000269|PubMed:21795683, CC ECO:0000269|PubMed:23639800, ECO:0000269|PubMed:9396714, CC ECO:0000269|PubMed:9478986}. CC -!- FUNCTION: [Isoform 3]: Non functional nucleoside transporter protein CC for adenosine or thymidine transport. Does not express on cell CC membrane. {ECO:0000269|PubMed:12527552}. CC -!- CATALYTIC ACTIVITY: CC Reaction=inosine(in) = inosine(out); Xref=Rhea:RHEA:75375, CC ChEBI:CHEBI:17596; Evidence={ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12527552, ECO:0000269|PubMed:16214850}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75376; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12527552, CC ECO:0000305|PubMed:16214850}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:75377; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12527552, CC ECO:0000305|PubMed:16214850}; CC -!- CATALYTIC ACTIVITY: CC Reaction=adenosine(in) = adenosine(out); Xref=Rhea:RHEA:75343, CC ChEBI:CHEBI:16335; Evidence={ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12527552}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75344; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12527552}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:75345; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12527552}; CC -!- CATALYTIC ACTIVITY: CC Reaction=uridine(out) = uridine(in); Xref=Rhea:RHEA:71519, CC ChEBI:CHEBI:16704; Evidence={ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12590919, ECO:0000269|PubMed:16214850, CC ECO:0000269|PubMed:21795683, ECO:0000269|PubMed:9396714, CC ECO:0000269|PubMed:9478986}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71520; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12527552, CC ECO:0000305|PubMed:16214850, ECO:0000305|PubMed:21795683, CC ECO:0000305|PubMed:9396714, ECO:0000305|PubMed:9478986}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71521; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12527552, CC ECO:0000305|PubMed:16214850, ECO:0000305|PubMed:21795683, CC ECO:0000305|PubMed:9396714, ECO:0000305|PubMed:9478986}; CC -!- CATALYTIC ACTIVITY: CC Reaction=thymidine(in) = thymidine(out); Xref=Rhea:RHEA:75363, CC ChEBI:CHEBI:17748; Evidence={ECO:0000269|PubMed:12527552}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75364; CC Evidence={ECO:0000305|PubMed:12527552}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:75365; CC Evidence={ECO:0000305|PubMed:12527552}; CC -!- CATALYTIC ACTIVITY: CC Reaction=hypoxanthine(out) = hypoxanthine(in); Xref=Rhea:RHEA:71515, CC ChEBI:CHEBI:17368; Evidence={ECO:0000269|PubMed:16214850, CC ECO:0000269|PubMed:21795683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71516; CC Evidence={ECO:0000305|PubMed:16214850, ECO:0000305|PubMed:21795683}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71517; CC Evidence={ECO:0000305|PubMed:16214850, ECO:0000305|PubMed:21795683}; CC -!- CATALYTIC ACTIVITY: CC Reaction=adenine(out) = adenine(in); Xref=Rhea:RHEA:71523, CC ChEBI:CHEBI:16708; Evidence={ECO:0000269|PubMed:21795683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71524; CC Evidence={ECO:0000305|PubMed:21795683}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71525; CC Evidence={ECO:0000305|PubMed:21795683}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(in) = cytidine(out); Xref=Rhea:RHEA:75367, CC ChEBI:CHEBI:17562; Evidence={ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12590919}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75368; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12590919}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:75369; CC Evidence={ECO:0000305|PubMed:10722669, ECO:0000305|PubMed:12590919}; CC -!- CATALYTIC ACTIVITY: CC Reaction=thymine(out) = thymine(in); Xref=Rhea:RHEA:71527, CC ChEBI:CHEBI:17821; Evidence={ECO:0000269|PubMed:21795683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71528; CC Evidence={ECO:0000305|PubMed:21795683}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71529; CC Evidence={ECO:0000305|PubMed:21795683}; CC -!- CATALYTIC ACTIVITY: CC Reaction=uracil(in) = uracil(out); Xref=Rhea:RHEA:69404, CC ChEBI:CHEBI:17568; Evidence={ECO:0000269|PubMed:21795683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69405; CC Evidence={ECO:0000305|PubMed:21795683}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69406; CC Evidence={ECO:0000305|PubMed:21795683}; CC -!- CATALYTIC ACTIVITY: CC Reaction=guanine(out) = guanine(in); Xref=Rhea:RHEA:71531, CC ChEBI:CHEBI:16235; Evidence={ECO:0000269|PubMed:21795683}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71532; CC Evidence={ECO:0000305|PubMed:21795683}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71533; CC Evidence={ECO:0000305|PubMed:21795683}; CC -!- CATALYTIC ACTIVITY: CC Reaction=guanosine(in) = guanosine(out); Xref=Rhea:RHEA:75371, CC ChEBI:CHEBI:16750; Evidence={ECO:0000269|PubMed:16214850}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75372; CC Evidence={ECO:0000305|PubMed:16214850}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:75373; CC Evidence={ECO:0000305|PubMed:16214850}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=50 uM for inosine {ECO:0000269|PubMed:10722669}; CC KM=75.9 uM for adenosine {ECO:0000269|PubMed:12527552}; CC KM=140 uM for adenosine {ECO:0000269|PubMed:10722669}; CC KM=200 uM for uridine {ECO:0000269|PubMed:9396714}; CC KM=250 uM for uridine {ECO:0000269|PubMed:10722669}; CC KM=330 uM for uridine {ECO:0000269|PubMed:12590919}; CC KM=500 uM for uridine {ECO:0000269|PubMed:21795683}; CC KM=710 uM for thymidine {ECO:0000269|PubMed:10722669}; CC KM=1500 uM for hypoxanthine {ECO:0000269|PubMed:21795683}; CC KM=1800 uM for adenine {ECO:0000269|PubMed:21795683}; CC KM=3900 uM for cytidine {ECO:0000269|PubMed:12590919}; CC KM=5610 uM for cytidine {ECO:0000269|PubMed:10722669}; CC KM=6000 uM for thymine {ECO:0000269|PubMed:21795683}; CC Vmax=72 pmol/min/mg enzyme for inosine uptake CC {ECO:0000269|PubMed:10722669}; CC Vmax=1147 pmol/min/mg enzyme for adenosine uptake CC {ECO:0000269|PubMed:10722669}; CC Vmax=2055 pmol/min/mg enzyme for uridine uptake CC {ECO:0000269|PubMed:10722669}; CC Vmax=2486 pmol/min/mg enzyme for thymidine uptake CC {ECO:0000269|PubMed:10722669}; CC Vmax=9740 pmol/min/mg enzyme for cytidine uptake CC {ECO:0000269|PubMed:10722669}; CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:23639800}; Multi-pass membrane protein CC {ECO:0000305}. Basolateral cell membrane {ECO:0000269|PubMed:12527552}; CC Multi-pass membrane protein {ECO:0000305}. Note=Localized to the apical CC membrane of Sertoli cells. {ECO:0000269|PubMed:23639800}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Long; CC IsoId=Q14542-1; Sequence=Displayed; CC Name=2; Synonyms=Short, HNP36; CC IsoId=Q14542-2; Sequence=VSP_040728, VSP_040729; CC Name=3; Synonyms=hENT2A; CC IsoId=Q14542-3; Sequence=VSP_040730, VSP_040731; CC Name=4; CC IsoId=Q14542-4; Sequence=VSP_061920; CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle CC (PubMed:9478986). Expressed in liver, lung, placenta, brain, heart, CC kidney and ovarian tissues (PubMed:9478986). Expressed in testis at the CC blood-brain-barrier (PubMed:23639800). {ECO:0000269|PubMed:23639800, CC ECO:0000269|PubMed:9478986}. CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12590919}. CC -!- MISCELLANEOUS: Transport activity is insensitive to nanomolar CC concentrations of the inhibitor nitrobenzylmercaptopurine riboside CC (NBMPR) (PubMed:9396714, PubMed:9478986, PubMed:10722669, CC PubMed:12590919, PubMed:21795683). Inhibited by higher concentrations CC of NBMPR (1uM-10uM) (PubMed:9396714, PubMed:9478986, PubMed:10722669, CC PubMed:12590919). {ECO:0000269|PubMed:10722669, CC ECO:0000269|PubMed:12590919, ECO:0000269|PubMed:21795683, CC ECO:0000269|PubMed:9396714, ECO:0000269|PubMed:9478986}. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the SLC29A/ENT transporter (TC 2.A.57) family. CC {ECO:0000305}. CC -!- CAUTION: The nuclear function of SLC29A2/ENT2 is unclear. A study CC reported that under proliferative conditions, two SLC29A2/ENT2 nuclear CC isoforms recruited SLC29A2/ENT2 to the nuclear envelope in order to CC translocate nucleosides into the nucleus for incorporation into DNA CC during replication (PubMed:27271752). However, the physiological CC existence of these isoforms has yet to be proven. CC {ECO:0000269|PubMed:27271752, ECO:0000305|PubMed:27271752}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA60380.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X86681; CAA60380.1; ALT_SEQ; mRNA. DR EMBL; AF029358; AAC39526.1; -; mRNA. DR EMBL; AF034102; AAB97834.1; -; mRNA. DR EMBL; AK057041; BAG51849.1; -; mRNA. DR EMBL; AF401235; AAK92533.1; -; mRNA. DR EMBL; AP001107; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW74521.1; -; Genomic_DNA. DR EMBL; CH471076; EAW74519.1; -; Genomic_DNA. DR EMBL; CH471076; EAW74522.1; -; Genomic_DNA. DR EMBL; BC093634; AAH93634.1; -; mRNA. DR CCDS; CCDS73326.1; -. [Q14542-4] DR CCDS; CCDS8137.1; -. [Q14542-1] DR PIR; JC4196; JC4196. DR RefSeq; NP_001287797.1; NM_001300868.1. [Q14542-1] DR RefSeq; NP_001287798.1; NM_001300869.1. [Q14542-4] DR RefSeq; NP_001523.2; NM_001532.2. [Q14542-1] DR RefSeq; XP_016873121.1; XM_017017632.1. [Q14542-1] DR RefSeq; XP_016873126.1; XM_017017637.1. DR AlphaFoldDB; Q14542; -. DR SMR; Q14542; -. DR BioGRID; 109419; 26. DR IntAct; Q14542; 2. DR MINT; Q14542; -. DR STRING; 9606.ENSP00000440329; -. DR BindingDB; Q14542; -. DR ChEMBL; CHEMBL3509606; -. DR DrugBank; DB00640; Adenosine. DR DrugBank; DB00993; Azathioprine. DR DrugBank; DB00900; Didanosine. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB00441; Gemcitabine. DR DrugBank; DB01033; Mercaptopurine. DR DrugBank; DB09327; Tegafur-uracil. DR DrugBank; DB00432; Trifluridine. DR DrugBank; DB00943; Zalcitabine. DR DrugBank; DB00495; Zidovudine. DR TCDB; 2.A.57.1.8; the equilibrative nucleoside transporter (ent) family. DR GlyCosmos; Q14542; 3 sites, No reported glycans. DR GlyGen; Q14542; 3 sites. DR iPTMnet; Q14542; -. DR PhosphoSitePlus; Q14542; -. DR SwissPalm; Q14542; -. DR BioMuta; SLC29A2; -. DR DMDM; 116242781; -. DR EPD; Q14542; -. DR jPOST; Q14542; -. DR MassIVE; Q14542; -. DR MaxQB; Q14542; -. DR PaxDb; 9606-ENSP00000350024; -. DR PeptideAtlas; Q14542; -. DR ProteomicsDB; 33823; -. DR ProteomicsDB; 60037; -. [Q14542-1] DR ProteomicsDB; 60039; -. [Q14542-3] DR Pumba; Q14542; -. DR Antibodypedia; 16257; 175 antibodies from 23 providers. DR DNASU; 3177; -. DR Ensembl; ENST00000311161.11; ENSP00000311250.7; ENSG00000174669.12. [Q14542-4] DR Ensembl; ENST00000357440.7; ENSP00000350024.2; ENSG00000174669.12. [Q14542-1] DR Ensembl; ENST00000540386.5; ENSP00000444870.1; ENSG00000174669.12. [Q14542-3] DR Ensembl; ENST00000541567.5; ENSP00000442116.1; ENSG00000174669.12. [Q14542-2] DR Ensembl; ENST00000544554.5; ENSP00000439456.1; ENSG00000174669.12. [Q14542-1] DR Ensembl; ENST00000546034.1; ENSP00000440329.1; ENSG00000174669.12. [Q14542-1] DR Ensembl; ENST00000619145.4; ENSP00000481944.1; ENSG00000174669.12. [Q14542-4] DR GeneID; 3177; -. DR KEGG; hsa:3177; -. DR MANE-Select; ENST00000357440.7; ENSP00000350024.2; NM_001532.3; NP_001523.2. DR UCSC; uc001oht.4; human. [Q14542-1] DR AGR; HGNC:11004; -. DR CTD; 3177; -. DR DisGeNET; 3177; -. DR GeneCards; SLC29A2; -. DR HGNC; HGNC:11004; SLC29A2. DR HPA; ENSG00000174669; Group enriched (skeletal muscle, tongue). DR MIM; 602110; gene. DR neXtProt; NX_Q14542; -. DR OpenTargets; ENSG00000174669; -. DR PharmGKB; PA191; -. DR VEuPathDB; HostDB:ENSG00000174669; -. DR eggNOG; KOG1479; Eukaryota. DR GeneTree; ENSGT00950000182898; -. DR HOGENOM; CLU_021611_6_0_1; -. DR InParanoid; Q14542; -. DR OMA; FNIMDWV; -. DR OrthoDB; 517168at2759; -. DR PhylomeDB; Q14542; -. DR TreeFam; TF313950; -. DR PathwayCommons; Q14542; -. DR Reactome; R-HSA-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane. DR Reactome; R-HSA-9748787; Azathioprine ADME. DR SignaLink; Q14542; -. DR BioGRID-ORCS; 3177; 16 hits in 1155 CRISPR screens. DR ChiTaRS; SLC29A2; human. DR GeneWiki; Equilibrative_nucleoside_transporter_2; -. DR GenomeRNAi; 3177; -. DR Pharos; Q14542; Tbio. DR PRO; PR:Q14542; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q14542; Protein. DR Bgee; ENSG00000174669; Expressed in gastrocnemius and 149 other cell types or tissues. DR ExpressionAtlas; Q14542; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0015207; F:adenine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015212; F:cytidine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015208; F:guanine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015205; F:nucleobase transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015211; F:purine nucleoside transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015210; F:uracil transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015213; F:uridine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015853; P:adenine transport; IDA:UniProtKB. DR GO; GO:0032238; P:adenosine transport; IDA:UniProtKB. DR GO; GO:0015861; P:cytidine transport; IDA:UniProtKB. DR GO; GO:1903716; P:guanine transmembrane transport; IDA:UniProtKB. DR GO; GO:0015854; P:guanine transport; IBA:GO_Central. DR GO; GO:0035344; P:hypoxanthine transport; IDA:UniProtKB. DR GO; GO:0035340; P:inosine transport; IDA:UniProtKB. DR GO; GO:0006836; P:neurotransmitter transport; IDA:ARUK-UCL. DR GO; GO:0001504; P:neurotransmitter uptake; ISS:ARUK-UCL. DR GO; GO:0015851; P:nucleobase transport; IDA:UniProtKB. DR GO; GO:1901642; P:nucleoside transmembrane transport; IDA:UniProtKB. DR GO; GO:0015858; P:nucleoside transport; IDA:UniProtKB. DR GO; GO:1904823; P:purine nucleobase transmembrane transport; IDA:UniProtKB. DR GO; GO:0015860; P:purine nucleoside transmembrane transport; IDA:ARUK-UCL. DR GO; GO:0072531; P:pyrimidine-containing compound transmembrane transport; IDA:ARUK-UCL. DR GO; GO:0035364; P:thymine transport; IDA:UniProtKB. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:1903791; P:uracil transmembrane transport; IDA:UniProtKB. DR GO; GO:0015862; P:uridine transport; IDA:UniProtKB. DR GO; GO:0006855; P:xenobiotic transmembrane transport; TAS:Reactome. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR034764; ENT1/ENT2. DR InterPro; IPR002259; Eqnu_transpt. DR InterPro; IPR036259; MFS_trans_sf. DR NCBIfam; TIGR00939; 2a57; 1. DR PANTHER; PTHR10332; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER; 1. DR PANTHER; PTHR10332:SF8; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 2; 1. DR Pfam; PF01733; Nucleoside_tran; 1. DR PIRSF; PIRSF016379; ENT; 1. DR PRINTS; PR01130; DERENTRNSPRT. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR Genevisible; Q14542; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Glycoprotein; Membrane; KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..456 FT /note="Equilibrative nucleoside transporter 2" FT /id="PRO_0000209340" FT TRANSMEM 13..33 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 70..90 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 99..119 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 124..144 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 162..182 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 193..213 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 291..311 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 324..344 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 360..380 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 386..406 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 432..452 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 252 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12590919" FT CARBOHYD 57 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12590919" FT CARBOHYD 225 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 93..202 FT /note="VPETVRILGSLLAILLLFALTAALVKVDMSPGPFFSITMASVCFINSFSAVL FT QGSLFGQLGTMPSTYSTLFLSGQGLAGIFAALAMLLSMASGVDAETSALGYFITPCVG FT -> AGQGGHEPRTLLLHHHGLRLLHQLLQCSPTGQPLRAAGHHALHLQHPLPQRPGPGW FT DLCCPCHAPVHGQWRGRRDLCPGVLYHALCGHPHVHRVLPEPASPEVCPLLPGQ (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:7639753" FT /id="VSP_040728" FT VAR_SEQ 203..456 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7639753" FT /id="VSP_040729" FT VAR_SEQ 246..456 FT /note="ENGIPSSPQKVALTLDLDLEKEPESEPDEPQKPGKPSVFTVFQKIWLTALCL FT VLVFTVTLSVFPAITAMVTSSTSPGKWSQFFNPICCFLLFNIMDWLGRSLTSYFLWPDE FT DSRLLPLLVCLRFLFVPLFMLCHVPQRSRLPILFPQDAYFITFMLLFAVSNGYLVSLTM FT CLAPRQVLPHEREVAGALMTFFLALGLSCGASLSFLFKALL -> LADSAVPCVGLHSH FT PVRLPRHHSHGDQLHQSWEVESVLQPHLLLPPLQHHGLAGTEPDLLLPVARRGQPAAAP FT AGLPAVPVRAPLHAVPRAPEVPAAHPLPTGCLLHHLHAALCRF (in isoform 4)" FT /id="VSP_061920" FT VAR_SEQ 290..301 FT /note="IWLTALCLVLVF -> SPCPSSPPSQPW (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12527552" FT /id="VSP_040730" FT VAR_SEQ 302..456 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12527552" FT /id="VSP_040731" FT VARIANT 5 FT /note="D -> Y (decreased nucleoside and nucleobase FT transport; dbSNP:rs8187643)" FT /evidence="ECO:0000269|PubMed:16214850" FT /id="VAR_029289" FT VARIANT 68 FT /note="N -> K (no change in nucleoside and nucleobase FT transport; dbSNP:rs8187644)" FT /evidence="ECO:0000269|PubMed:16214850" FT /id="VAR_029290" FT VARIANT 94 FT /note="P -> L (no change in nucleoside and nucleobase FT transport; dbSNP:rs8187648)" FT /evidence="ECO:0000269|PubMed:16214850" FT /id="VAR_029291" FT VARIANT 184..186 FT /note="SGV -> M (decreased inosine and guanosine transport; FT no change in uridine and hypoxanthine transport)" FT /evidence="ECO:0000269|PubMed:16214850" FT /id="VAR_036822" FT MUTAGEN 48 FT /note="N->D: No difference in uridine or cytidine uptake. FT No differences in Km values and lower Vmax values for FT either uridine or cytidine uptake; when associated with FT D-57." FT /evidence="ECO:0000269|PubMed:12590919" FT MUTAGEN 57 FT /note="N->D: No difference in uridine or cytidine uptake. FT No differences in Km values and lower Vmax values for FT either uridine or cytidine uptake; when associated with FT D-48." FT /evidence="ECO:0000269|PubMed:12590919" FT MUTAGEN 455 FT /note="L->R: Reduces drastically localization at the cell FT surface. No effect on uptake of adenosine and thymidine. FT Reduces drastically localization at the cell surface and FT induces an significant reduction of adenosine or thymidine FT uptake; when associated with R-456." FT /evidence="ECO:0000269|PubMed:12527552" FT MUTAGEN 456 FT /note="L->R: Reduces drastically localization at the cell FT surface and induces an significant reduction of adenosine FT or thymidine uptake; when associated with R-455." FT /evidence="ECO:0000269|PubMed:12527552" FT CONFLICT 200 FT /note="C -> Y (in Ref. 1; CAA60380 and 2; AAC39526)" FT /evidence="ECO:0000305" SQ SEQUENCE 456 AA; 50113 MW; ABCBD244306708E1 CRC64; MARGDAPRDS YHLVGISFFI LGLGTLLPWN FFITAIPYFQ ARLAGAGNST ARILSTNHTG PEDAFNFNNW VTLLSQLPLL LFTLLNSFLY QCVPETVRIL GSLLAILLLF ALTAALVKVD MSPGPFFSIT MASVCFINSF SAVLQGSLFG QLGTMPSTYS TLFLSGQGLA GIFAALAMLL SMASGVDAET SALGYFITPC VGILMSIVCY LSLPHLKFAR YYLANKSSQA QAQELETKAE LLQSDENGIP SSPQKVALTL DLDLEKEPES EPDEPQKPGK PSVFTVFQKI WLTALCLVLV FTVTLSVFPA ITAMVTSSTS PGKWSQFFNP ICCFLLFNIM DWLGRSLTSY FLWPDEDSRL LPLLVCLRFL FVPLFMLCHV PQRSRLPILF PQDAYFITFM LLFAVSNGYL VSLTMCLAPR QVLPHEREVA GALMTFFLAL GLSCGASLSF LFKALL //