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2.A.41.2.6
Broad-specificity nucleoside:Na+, H+ and Li+ symporter, hCNT3 (Slc28a3) transports a broad range of both purine and pyrimidine nucleosides as well as anticancer and antiviral nucleoside drugs, but guanosine, 3'azido-3-deoxythymidine and 2',3'-dideoxycytidine, which are substrates with Na+, are not substrates with H+. Both of the two cation-binding sites can apparently bind Na+, but only one can bind H+, and the Na+ and H+ forms transport different ranges of substrates. (Note: Cnt1 and Cnt2 are Na+-specific.) (Smith et al., 2005).  (Na+/nucleoside = 2; Na+ + H+/nucleoside = 2; H+/nucleoside = 1).  The matricellular protein, cysteine-rich angiogenic inducer 61 (CYR61), negatively regulates synthesis of the nucleoside transporters hENT1 and hCNT3, both of which transport the anti-cancer agent, gemcitabine (Hesler et al. 2016). Also probably transports gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin and 3-deazauridine. Modeling revealed mobility of selected binding site and homotrimer interface residues (Latek 2017).

Accession Number:Q9ERH8
Protein Name:CNT3 aka SLC28A3
Length:703
Molecular Weight:78310.00
Species:Homo sapiens (Human) [10090]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Nucleosides, Na+, H+, Li+

Cross database links:

Genevestigator: Q9ERH8
eggNOG: roNOG07002
HEGENOM: HBG713614
RefSeq: NP_071712.3   
Entrez Gene ID: 114304   
Pfam: PF07670    PF07662    PF01773   
KEGG: mmu:114304   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0001882 F:nucleoside binding
GO:0015390 F:purine-specific nucleoside:sodium symporter...
GO:0015389 F:pyrimidine- and adenine-specific:sodium sym...
GO:0015860 P:purine nucleoside transport
GO:0015864 P:pyrimidine nucleoside transport

References (3)

[1] “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).”  Ritzel M.W.L.et.al.   11032837
[2] “The transcriptional landscape of the mammalian genome.”  Carninci P.et.al.   16141072
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSRADPGKNS EPSESKMSLE LRPTAPSDLG RSNEAFQDED LERQNTPGNS TVRNRVVQSG 
61:	EQGHAKQDDR QITIEQEPLG NKEDPEDDSE DEHQKGFLER KYDTICEFCR KHRVVLRSTI 
121:	WAVLLTGFLA LVIAACAINF HRALPLFVIT LVTIFFVIWD HLMAKYEQRI DDFLSPGRRL 
181:	LDRHWFWLKW VVWSSLILAI ILWLSLDTAK LGQQNLVSFG GLIMYLILLF LFSKHPTRVY 
241:	WRPVFWGIGL QFLLGLLILR TRPGFVAFDW MGRQVQTFLG YTDTGARFVF GEKYTDHFFA 
301:	FKILPIVVFF STVMSMLYYL GLMQWIIRKV GWLMLVTMGS SPIESVVAAG NIFIGQTESP 
361:	LLVQPYLPHV TKSELHTIMT AGFATIAGSV LGAYISFGVS STHLLTASVM SAPAALAVAK 
421:	LFWPETEKPK ITLKSAMKME NGDSRNLLEA ASQGASSSIP LVANIAANLI AFLALLSFVN 
481:	SALSWFGSMF NYPELSFELI CSYIFMPFSF MMGVDWQDSF MVAKLIGYKT FFNEFVAYDH 
541:	LSKLINLRKA AGPKFVNGVQ QYMSIRSETI ATYALCGFAN FGSLGIVIGG LTSIAPSRKR 
601:	DIASGAMRAL IAGTIACFMT ACIAGILSDT PVDINCHHVL ENGRVLSNTT EVVSCCQNLF 
661:	NSTVAKGPND VVPGGNFSLY ALKSCCNLLK PPTLNCNWIP NKL