S28A2_HUMAN
ID S28A2_HUMAN Reviewed; 658 AA.
AC O43868; A8K7F9; O43239; Q52LZ0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Sodium/nucleoside cotransporter 2;
DE AltName: Full=Concentrative nucleoside transporter 2;
DE Short=CNT 2;
DE Short=hCNT2;
DE AltName: Full=Na(+)/nucleoside cotransporter 2;
DE AltName: Full=Sodium-coupled nucleoside transporter 2;
DE AltName: Full=Sodium/purine nucleoside co-transporter {ECO:0000303|PubMed:9435697};
DE Short=SPNT {ECO:0000303|PubMed:9435697};
DE AltName: Full=Solute carrier family 28 member 2;
GN Name=SLC28A2; Synonyms=CNT2;
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], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=9435697; DOI=10.1152/ajprenal.1997.273.6.f1058;
RA Wang J., Su S.-F., Dresser M.J., Schaner M.E., Washington C.B.,
RA Giacomini K.M.;
RT "Na+-dependent purine nucleoside transporter from human kidney: cloning and
RT functional characterization.";
RL Am. J. Physiol. 273:F1058-F1065(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, AND VARIANT
RP ARG-75.
RC TISSUE=Small intestine;
RX PubMed=10087507; DOI=10.3109/09687689709044322;
RA Ritzel M.W.L., Yao S.Y.M., Ng A.M.L., Mackey J.R., Cass C.E., Young J.D.;
RT "Molecular cloning, functional expression and chromosomal localization of a
RT cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for
RT purine nucleosides and uridine.";
RL Mol. Membr. Biol. 15:203-211(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP MUTAGENESIS.
RX PubMed=10455109; DOI=10.1074/jbc.274.35.24475;
RA Loewen S.K., Ng A.M.L., Yao S.Y.M., Cass C.E., Baldwin S.A., Young J.D.;
RT "Identification of amino acid residues responsible for the pyrimidine and
RT purine nucleoside specificities of human concentrative Na(+) nucleoside
RT cotransporters hCNT1 and hCNT2.";
RL J. Biol. Chem. 274:24475-24484(1999).
RN [6]
RP VARIANTS LEU-22; ARG-75; TRP-163; THR-245; SER-355 AND PHE-462.
RX PubMed=15861032; DOI=10.1097/01213011-200502000-00004;
RA Owen R.P., Gray J.H., Taylor T.R., Carlson E.J., Huang C.C., Kawamoto M.,
RA Johns S.J., Stryke D., Ferrin T.E., Giacomini K.M.;
RT "Genetic analysis and functional characterization of polymorphisms in the
RT human concentrative nucleoside transporter, CNT2.";
RL Pharmacogenet. Genomics 15:83-90(2005).
RN [7]
RP VARIANTS PRO-12; LEU-22; ARG-75; HIS-142; TRP-163; ASP-172; LYS-385 AND
RP THR-612.
RX PubMed=17700367; DOI=10.1097/fpc.0b013e3281c10e41;
RA Li L., Tan C.M.F., Koo S.H., Chong K.T., Lee E.J.D.;
RT "Identification and functional analysis of variants in the human
RT concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays
RT and Indians.";
RL Pharmacogenet. Genomics 17:783-786(2007).
CC -!- FUNCTION: Sodium-dependent and purine-selective transporter
CC (PubMed:9435697, PubMed:10087507). Exhibits the transport
CC characteristics of the nucleoside transport system cif or N1 subtype
CC (N1/cif) (selective for purine nucleosides and uridine)
CC (PubMed:9435697, PubMed:10087507). Plays a critical role in specific
CC uptake and salvage of purine nucleosides in kidney and other tissues
CC (PubMed:9435697). {ECO:0000269|PubMed:10087507,
CC ECO:0000269|PubMed:9435697}.
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:10087507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine(out) + Na(+)(out) = inosine(in) + Na(+)(in);
CC Xref=Rhea:RHEA:69931, ChEBI:CHEBI:17596, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:10087507, ECO:0000269|PubMed:9435697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine(out) + Na(+)(out) = guanosine(in) + Na(+)(in);
CC Xref=Rhea:RHEA:69935, ChEBI:CHEBI:16750, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:10087507};
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:10087507, ECO:0000269|PubMed:9435697};
CC -!- ACTIVITY REGULATION: Inhibited by formycin B.
CC {ECO:0000269|PubMed:9435697}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:9435697}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in heart and skeletal muscle followed by
CC liver, kidney, intestine, pancreas, placenta and brain
CC (PubMed:9435697). Weak expression in lung (PubMed:9435697).
CC {ECO:0000269|PubMed:9435697}.
CC -!- SIMILARITY: Belongs to the concentrative nucleoside transporter (CNT)
CC (TC 2.A.41) family. {ECO:0000305}.
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DR EMBL; U84392; AAC51930.1; -; mRNA.
DR EMBL; AF036109; AAB88539.1; -; mRNA.
DR EMBL; AK291974; BAF84663.1; -; mRNA.
DR EMBL; BC093737; AAH93737.1; -; mRNA.
DR CCDS; CCDS10121.1; -.
DR RefSeq; NP_004203.2; NM_004212.3.
DR RefSeq; XP_011520500.1; XM_011522198.2.
DR AlphaFoldDB; O43868; -.
DR SMR; O43868; -.
DR BioGRID; 114600; 16.
DR STRING; 9606.ENSP00000315006; -.
DR BindingDB; O43868; -.
DR ChEMBL; CHEMBL5780; -.
DR DrugBank; DB00640; Adenosine.
DR DrugBank; DB01033; Mercaptopurine.
DR DrugBank; DB09327; Tegafur-uracil.
DR GuidetoPHARMACOLOGY; 1115; -.
DR TCDB; 2.A.41.2.4; the concentrative nucleoside transporter (cnt) family.
DR CarbonylDB; O43868; -.
DR iPTMnet; O43868; -.
DR PhosphoSitePlus; O43868; -.
DR BioMuta; SLC28A2; -.
DR MassIVE; O43868; -.
DR PaxDb; O43868; -.
DR PeptideAtlas; O43868; -.
DR PRIDE; O43868; -.
DR ProteomicsDB; 49214; -.
DR Antibodypedia; 24414; 152 antibodies from 27 providers.
DR DNASU; 9153; -.
DR Ensembl; ENST00000347644.8; ENSP00000315006.4; ENSG00000137860.12.
DR GeneID; 9153; -.
DR KEGG; hsa:9153; -.
DR MANE-Select; ENST00000347644.8; ENSP00000315006.4; NM_004212.4; NP_004203.2.
DR UCSC; uc001zva.3; human.
DR CTD; 9153; -.
DR DisGeNET; 9153; -.
DR GeneCards; SLC28A2; -.
DR HGNC; HGNC:11002; SLC28A2.
DR HPA; ENSG00000137860; Tissue enriched (intestine).
DR MIM; 606208; gene.
DR neXtProt; NX_O43868; -.
DR OpenTargets; ENSG00000137860; -.
DR PharmGKB; PA386; -.
DR VEuPathDB; HostDB:ENSG00000137860; -.
DR eggNOG; KOG3747; Eukaryota.
DR GeneTree; ENSGT00390000016025; -.
DR HOGENOM; CLU_016813_3_2_1; -.
DR InParanoid; O43868; -.
DR OMA; FITGQPK; -.
DR OrthoDB; 471043at2759; -.
DR PhylomeDB; O43868; -.
DR TreeFam; TF314131; -.
DR PathwayCommons; O43868; -.
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 BioGRID-ORCS; 9153; 9 hits in 1062 CRISPR screens.
DR GeneWiki; Concentrative_nucleoside_transporter_2; -.
DR GenomeRNAi; 9153; -.
DR Pharos; O43868; Tchem.
DR PRO; PR:O43868; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O43868; protein.
DR Bgee; ENSG00000137860; Expressed in jejunal mucosa and 91 other tissues.
DR ExpressionAtlas; O43868; baseline and differential.
DR Genevisible; O43868; HS.
DR GO; GO:0031526; C:brush border membrane; ISS:ARUK-UCL.
DR GO; GO:0030135; C:coated vesicle; ISS:ARUK-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0012506; C:vesicle membrane; ISS:ARUK-UCL.
DR GO; GO:1901474; F:azole transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005415; F:nucleoside:sodium symporter activity; IDA:ARUK-UCL.
DR GO; GO:0005345; F:purine nucleobase transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015211; F:purine nucleoside transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015389; F:pyrimidine- and adenine-specific:sodium symporter activity; IDA:ARUK-UCL.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0015213; F:uridine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0032238; P:adenosine transport; IDA:ARUK-UCL.
DR GO; GO:0045117; P:azole transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0035340; P:inosine transport; IDA:ARUK-UCL.
DR GO; GO:0006836; P:neurotransmitter transport; IDA:ARUK-UCL.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:1901642; P:nucleoside transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:1904823; P:purine nucleobase transmembrane transport; IDA:ARUK-UCL.
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:0001895; P:retina homeostasis; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0015862; P:uridine transport; IDA:ARUK-UCL.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; TAS:Reactome.
DR InterPro; IPR008276; C_nuclsd_transpt.
DR InterPro; IPR018270; C_nuclsd_transpt_met_bac.
DR InterPro; IPR030212; CNT1/CNT2.
DR InterPro; IPR011657; CNT_C_dom.
DR InterPro; IPR002668; CNT_N_dom.
DR InterPro; IPR011642; Gate_dom.
DR PANTHER; PTHR10590; PTHR10590; 1.
DR PANTHER; PTHR10590:SF11; PTHR10590:SF11; 1.
DR Pfam; PF07670; Gate; 1.
DR Pfam; PF07662; Nucleos_tra2_C; 1.
DR Pfam; PF01773; Nucleos_tra2_N; 1.
DR TIGRFAMs; TIGR00804; nupC; 1.
PE 2: Evidence at transcript level;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..658
FT /note="Sodium/nucleoside cotransporter 2"
FT /id="PRO_0000070450"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..314
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..355
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 567..587
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62773"
FT VARIANT 12
FT /note="L -> P (in dbSNP:rs567096708)"
FT /evidence="ECO:0000269|PubMed:17700367"
FT /id="VAR_036817"
FT VARIANT 22
FT /note="P -> L (in dbSNP:rs11854484)"
FT /evidence="ECO:0000269|PubMed:15861032,
FT ECO:0000269|PubMed:17700367"
FT /id="VAR_024639"
FT VARIANT 75
FT /note="S -> R (in dbSNP:rs1060896)"
FT /evidence="ECO:0000269|PubMed:10087507,
FT ECO:0000269|PubMed:15861032, ECO:0000269|PubMed:17700367"
FT /id="VAR_024640"
FT VARIANT 142
FT /note="R -> H (in dbSNP:rs115740452)"
FT /evidence="ECO:0000269|PubMed:17700367"
FT /id="VAR_036818"
FT VARIANT 163
FT /note="L -> W (in dbSNP:rs2271437)"
FT /evidence="ECO:0000269|PubMed:15861032,
FT ECO:0000269|PubMed:17700367"
FT /id="VAR_022001"
FT VARIANT 172
FT /note="E -> D (in dbSNP:rs113624548)"
FT /evidence="ECO:0000269|PubMed:17700367"
FT /id="VAR_036819"
FT VARIANT 245
FT /note="S -> T (in dbSNP:rs10519020)"
FT /evidence="ECO:0000269|PubMed:15861032"
FT /id="VAR_024641"
FT VARIANT 355
FT /note="F -> S (in dbSNP:rs17215633)"
FT /evidence="ECO:0000269|PubMed:15861032"
FT /id="VAR_024642"
FT VARIANT 385
FT /note="E -> K (in dbSNP:rs376327143)"
FT /evidence="ECO:0000269|PubMed:17700367"
FT /id="VAR_036820"
FT VARIANT 462
FT /note="L -> F (in dbSNP:rs17222057)"
FT /evidence="ECO:0000269|PubMed:15861032"
FT /id="VAR_024643"
FT VARIANT 509
FT /note="G -> E (in dbSNP:rs9635306)"
FT /id="VAR_028724"
FT VARIANT 612
FT /note="M -> T (in dbSNP:rs373539209)"
FT /evidence="ECO:0000269|PubMed:17700367"
FT /id="VAR_036821"
SQ SEQUENCE 658 AA; 71926 MW; 273545EE75E0D663 CRC64;
MEKASGRQSI ALSTVETGTV NPGLELMEKE VEPEGSKRTD AQGHSLGDGL GPSTYQRRSR
WPFSKARSFC KTHASLFKKI LLGLLCLAYA AYLLAACILN FQRALALFVI TCLVIFVLVH
SFLKKLLGKK LTRCLKPFEN SRLRLWTKWV FAGVSLVGLI LWLALDTAQR PEQLIPFAGI
CMFILILFAC SKHHSAVSWR TVFSGLGLQF VFGILVIRTD LGYTVFQWLG EQVQIFLNYT
VAGSSFVFGD TLVKDVFAFQ ALPIIIFFGC VVSILYYLGL VQWVVQKVAW FLQITMGTTA
TETLAVAGNI FVGMTEAPLL IRPYLGDMTL SEIHAVMTGG FATISGTVLG AFIAFGVDAS
SLISASVMAA PCALASSKLA YPEVEESKFK SEEGVKLPRG KERNVLEAAS NGAVDAIGLA
TNVAANLIAF LAVLAFINAA LSWLGELVDI QGLTFQVICS YLLRPMVFMM GVEWTDCPMV
AEMVGIKFFI NEFVAYQQLS QYKNKRLSGM EEWIEGEKQW ISVRAEIITT FSLCGFANLS
SIGITLGGLT SIVPHRKSDL SKVVVRALFT GACVSLISAC MAGILYVPRG AEADCVSFPN
TSFTNRTYET YMCCRGLFQS TSLNGTNPPS FSGPWEDKEF SAMALTNCCG FYNNTVCA
