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Identification
HMDB Protein ID HMDBP03808
Secondary Accession Numbers
  • 9396
Name Solute carrier family 28 member 3
Synonyms
  1. CNT 3
  2. Concentrative Na(+)-nucleoside cotransporter 3
  3. hCNT3
Gene Name SLC28A3
Protein Type Transporter
Biological Properties
General Function Involved in nucleoside:sodium symporter activity
Specific Function Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtype (N3/cib) (with marked transport of both thymidine and inosine). Employs a 2:1 sodium/nucleoside ratio. Also able to transport gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin and 3-deazauridine
Pathways
  • Azathioprine Action Pathway
  • Gemcitabine Action Pathway
  • Gemcitabine Metabolism Pathway
  • Mercaptopurine Action Pathway
  • Mercaptopurine Metabolism Pathway
  • Thioguanine Action Pathway
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
binding
nucleoside binding
transmembrane transporter activity
substrate-specific transmembrane transporter activity
nucleobase, nucleoside, nucleotide and nucleic acid transmembrane transporter activity
nucleoside transmembrane transporter activity
nucleoside:sodium symporter activity
transporter activity
Process
establishment of localization
transport
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein (Potential)
Gene Properties
Chromosome Location Chromosome:9
Locus 9q22.2
SNPs SLC28A3
Gene Sequence
>2076 bp
ATGGAGCTGAGGAGTACAGCAGCCCCCAGAGCTGAGGGCTACAGCAACGTGGGCTTCCAG
AATGAAGAAAACTTTCTTGAGAACGAGAACACATCAGGAAACAACTCAATAAGAAGCAGA
GCTGTGCAAAGCAGGGAGCACACAAACACCAAACAGGATGAAGAACAGGTCACAGTTGAG
CAGGATTCTCCAAGAAACAGAGAACACATGGAGGATGATGATGAGGAGATGCAACAAAAA
GGGTGTTTGGAAAGGAGGTATGACACAGTATGTGGTTTCTGTAGGAAACACAAAACAACT
CTTCGGCACATCATCTGGGGCATTTTATTAGCAGGTTATCTGGTTATGGTGATTTCGGCC
TGTGTGCTGAACTTTCACAGAGCCCTTCCTCTTTTTGTGATCACCGTGGCTGCCATCTTC
TTTGTTGTCTGGGATCACCTGATGGCCAAATACGAACATCGAATTGATGAGATGCTGTCT
CCTGGCAGAAGGCTTCTAAACAGCCATTGGTTCTGGCTGAAGTGGGTGATCTGGAGCTCC
CTGGTCCTAGCAGTTATTTTCTGGTTGGCCTTTGACACTGCCAAATTGGGTCAACAGCAG
CTGGTGTCCTTCGGTGGGCTCATAATGTACATTGTCCTGTTATTTCTATTTTCCAAGTAC
CCAACCAGAGTTTACTGGAGACCTGTCTTATGGGGAATCGGGCTACAGTTTCTTCTTGGG
CTCTTGATTCTAAGGACTGACCCTGGATTTATAGCTTTTGATTGGTTGGGCAGACAAGTT
CAGACTTTTCTGGAGTACACAGATGCTGGTGCTTCATTTGTCTTTGGTGAGAAATACAAA
GACCACTTCTTTGCATTTAAGGTCCTGCCGATCGTGGTTTTCTTCAGCACTGTGATGTCC
ATGCTGTACTACCTGGGACTGATGCAGTGGATTATTAGAAAGGTTGGATGGATCATGCTA
GTTACTACGGGATCATCTCCTATTGAATCTGTAGTTGCTTCTGGCAATATATTTGTTGGA
CAAACGGAGTCTCCACTGCTGGTCCGACCATATTTACCTTACATCACCAAGTCTGAACTC
CACGCCATCATGACCGCCGGGTTCTCTACCATTGCTGGAAGCGTGCTAGGTGCATACATT
TCTTTTGGGGTTCCATCCTCCCACTTGTTAACAGCGTCAGTTATGTCAGCACCTGCGTCA
TTGGCTGCTGCTAAACTCTTTTGGCCTGAGACAGAAAAACCTAAAATAACCCTCAAGAAT
GCCATGAAAATGGAAAGTGGTGATTCAGGGAATCTTCTAGAAGCTGCAACACAGGGAGCA
TCCTCCTCCATCTCCCTGGTGGCCAACATCGCTGTGAATCTGATTGCCTTCCTGGCCCTG
CTGTCTTTTATGAATTCAGCCCTGTCCTGGTTTGGAAACATGTTTGACTACCCACAGCTG
AGTTTTGAGCTAATCTGCTCCTACATCTTCATGCCCTTTTCCTTCATGATGGGAGTGGAA
TGGCAGGACAGCTTTATGGTTGCCAGACTCATAGGTTATAAGACCTTCTTCAATGAATTT
GTGGCTTATGAGCACCTCTCAAAATGGATCCACTTGAGGAAAGAAGGTGGACCCAAATTT
GTAAACGGTGTGCAGCAATATATATCAATTCGTTCTGAGATAATCGCCACTTACGCTCTC
TGTGGTTTTGCCAATATCGGGTCCCTAGGAATCGTGATCGGCGGACTCACATCCATGGCT
CCTTCCAGAAAGCGTGATATCGCCTCGGGGGCAGTGAGAGCTCTGATTGCGGGGACCGTG
GCCTGCTTCATGACAGCCTGCATCGCAGGCATACTCTCCAGCACTCCTGTGGACATCAAC
TGCCATCACGTTTTAGAGAATGCCTTCAACTCCACTTTCCCTGGAAACACAACCAAGGTG
ATAGCTTGTTGCCAAAGTCTGTTGAGCAGCACTGTTGCCAAGGGTCCTGGTGAAGTCATC
CCAGGAGGAAACCACAGTCTGTATTCTTTGAAGGGCTGCTGCACATTGTTGAATCCATCG
ACCTTTAACTGCAATGGGATCTCTAATACATTTTGA
Protein Properties
Number of Residues 691
Molecular Weight 76929.6
Theoretical pI 7.67
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 103-123
  • 128-148
  • 171-191
  • 201-221
  • 224-244
  • 288-308
  • 315-335
  • 362-382
  • 389-409
  • 444-464
  • 480-500
  • 554-574
  • 594-614
Protein Sequence
>Solute carrier family 28 member 3
MELRSTAAPRAEGYSNVGFQNEENFLENENTSGNNSIRSRAVQSREHTNTKQDEEQVTVE
QDSPRNREHMEDDDEEMQQKGCLERRYDTVCGFCRKHKTTLRHIIWGILLAGYLVMVISA
CVLNFHRALPLFVITVAAIFFVVWDHLMAKYEHRIDEMLSPGRRLLNSHWFWLKWVIWSS
LVLAVIFWLAFDTAKLGQQQLVSFGGLIMYIVLLFLFSKYPTRVYWRPVLWGIGLQFLLG
LLILRTDPGFIAFDWLGRQVQTFLEYTDAGASFVFGEKYKDHFFAFKVLPIVVFFSTVMS
MLYYLGLMQWIIRKVGWIMLVTTGSSPIESVVASGNIFVGQTESPLLVRPYLPYITKSEL
HAIMTAGFSTIAGSVLGAYISFGVPSSHLLTASVMSAPASLAAAKLFWPETEKPKITLKN
AMKMESGDSGNLLEAATQGASSSISLVANIAVNLIAFLALLSFMNSALSWFGNMFDYPQL
SFELICSYIFMPFSFMMGVEWQDSFMVARLIGYKTFFNEFVAYEHLSKWIHLRKEGGPKF
VNGVQQYISIRSEIIATYALCGFANIGSLGIVIGGLTSMAPSRKRDIASGAVRALIAGTV
ACFMTACIAGILSSTPVDINCHHVLENAFNSTFPGNTTKVIACCQSLLSSTVAKGPGEVI
PGGNHSLYSLKGCCTLLNPSTFNCNGISNTF
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9HAS3
UniProtKB/Swiss-Prot Entry Name S28A3_HUMAN
PDB IDs Not Available
GenBank Gene ID AF305210
GeneCard ID SLC28A3
GenAtlas ID SLC28A3
HGNC ID HGNC:16484
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [PubMed:15164053 ]
  4. Ritzel MW, Ng AM, Yao SY, Graham K, Loewen SK, Smith KM, Ritzel RG, Mowles DA, Carpenter P, Chen XZ, Karpinski E, Hyde RJ, Baldwin SA, Cass CE, Young JD: Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J Biol Chem. 2001 Jan 26;276(4):2914-27. Epub 2000 Oct 13. [PubMed:11032837 ]
  5. Damaraju S, Zhang J, Visser F, Tackaberry T, Dufour J, Smith KM, Slugoski M, Ritzel MW, Baldwin SA, Young JD, Cass CE: Identification and functional characterization of variants in human concentrative nucleoside transporter 3, hCNT3 (SLC28A3), arising from single nucleotide polymorphisms in coding regions of the hCNT3 gene. Pharmacogenet Genomics. 2005 Mar;15(3):173-82. [PubMed:15861042 ]
  6. Hu H, Endres CJ, Chang C, Umapathy NS, Lee EW, Fei YJ, Itagaki S, Swaan PW, Ganapathy V, Unadkat JD: Electrophysiological characterization and modeling of the structure activity relationship of the human concentrative nucleoside transporter 3 (hCNT3). Mol Pharmacol. 2006 May;69(5):1542-53. Epub 2006 Jan 30. [PubMed:16446384 ]
  7. Yamamoto T, Kuniki K, Takekuma Y, Hirano T, Iseki K, Sugawara M: Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters. Eur J Pharmacol. 2007 Feb 14;557(1):1-8. Epub 2006 Nov 3. [PubMed:17140564 ]
  8. Badagnani I, Chan W, Castro RA, Brett CM, Huang CC, Stryke D, Kawamoto M, Johns SJ, Ferrin TE, Carlson EJ, Burchard EG, Giacomini KM: Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3). Pharmacogenomics J. 2005;5(3):157-65. [PubMed:15738947 ]
  9. Errasti-Murugarren E, Cano-Soldado P, Pastor-Anglada M, Casado FJ: Functional characterization of a nucleoside-derived drug transporter variant (hCNT3C602R) showing altered sodium-binding capacity. Mol Pharmacol. 2008 Feb;73(2):379-86. Epub 2007 Nov 9. [PubMed:17993510 ]