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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). The 3-D structure has been solved at 3.6 Å resolution by cryoEM (Zhou et al. 2020). As for its bacterial homologs, hCNT3 presents a trimeric architecture with additional N-terminal transmembrane helices to stabilize the conserved central domains. The conserved binding sites for the substrate and sodium ions unravel the selective nucleoside transport and distinct coupling mechanism (Zhou et al. 2020).

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:

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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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