Q9HAS3 (S28A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 28 member 3

Alternative name(s):
Concentrative Na(+)-nucleoside cotransporter 3
Short name=CNT 3
Short name=hCNT3

Gene names

Name:	SLC28A3
Synonyms:	CNT3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	691 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.1 Ref.7 Ref.8
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Expressed in pancreas, bone marrow, trachea, mammary gland, liver, prostate, and regions of intestine, brain, lung, placenta, testis, kidney, and heart. Ref.1
Induction	Up-regulated by phorbol myristate acetate (PMA) in HL-60 cells. Ref.1
Sequence similarities	Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family. [View classification]
Biophysicochemical properties	Kinetic parameters: KM=21.6 µM for uridine Ref.1 Ref.6 KM=15.4 µM for cytidine KM=21.2 µM for thymidine KM=15.1 µM for adenosine KM=43 µM for guanosine KM=52.5 µM for inosine Vmax=25.8 pmol/min/mg enzyme for uridine uptake Vmax=32.8 pmol/min/mg enzyme for cytidine uptake Vmax=24.2 pmol/min/mg enzyme for thymidine uptake Vmax=30.4 pmol/min/mg enzyme for adenosine uptake Vmax=51.4 pmol/min/mg enzyme for guanosine uptake Vmax=44.8 pmol/min/mg enzyme for inosine uptake

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	pyrimidine nucleoside transport Inferred from electronic annotation. Source: Compara transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	nucleoside binding Inferred from electronic annotation. Source: InterPro purine-specific nucleoside:sodium symporter activity Inferred from electronic annotation. Source: Compara pyrimidine- and adenine-specific:sodium symporter activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 691	691	Solute carrier family 28 member 3		PRO_0000324146
Regions
	Topological domain	1 – 102	102	Cytoplasmic Potential
	Transmembrane	103 – 123	21	Helical; Potential
	Topological domain	124 – 127	4	Extracellular Potential
	Transmembrane	128 – 148	21	Helical; Potential
	Topological domain	149 – 170	22	Cytoplasmic Potential
	Transmembrane	171 – 191	21	Helical; Potential
	Topological domain	192 – 200	9	Extracellular Potential
	Transmembrane	201 – 221	21	Helical; Potential
	Topological domain	222 – 223	2	Cytoplasmic Potential
	Transmembrane	224 – 244	21	Helical; Potential
	Topological domain	245 – 287	43	Extracellular Potential
	Transmembrane	288 – 308	21	Helical; Potential
	Topological domain	309 – 314	6	Cytoplasmic Potential
	Transmembrane	315 – 335	21	Helical; Potential
	Topological domain	336 – 361	26	Extracellular Potential
	Transmembrane	362 – 382	21	Helical; Potential
	Topological domain	383 – 388	6	Cytoplasmic Potential
	Transmembrane	389 – 409	21	Helical; Potential
	Topological domain	410 – 443	34	Extracellular Potential
	Transmembrane	444 – 464	21	Helical; Potential
	Topological domain	465 – 479	15	Cytoplasmic Potential
	Transmembrane	480 – 500	21	Helical; Potential
	Topological domain	501 – 553	53	Extracellular Potential
	Transmembrane	554 – 574	21	Helical; Potential
	Topological domain	575 – 593	19	Cytoplasmic Potential
	Transmembrane	594 – 614	21	Helical; Potential
	Topological domain	615 – 691	77	Extracellular Potential
Natural variations
	Natural variant	4	1	R → K. Ref.9		VAR_039665
	Natural variant	5	1	S → N. Ref.6 Ref.9 Corresponds to variant rs11568403 [ dbSNP | Ensembl ].		VAR_039666
	Natural variant	62	1	D → H. Ref.9 Corresponds to variant rs45621433 [ dbSNP | Ensembl ].		VAR_039667
	Natural variant	67	1	R → K. Ref.9		VAR_039668
	Natural variant	113	1	Y → C. Ref.9 Corresponds to variant rs10868138 [ dbSNP | Ensembl ].		VAR_039669
	Natural variant	131	1	L → F. Ref.6		VAR_039670
	Natural variant	221	1	P → Q. Corresponds to variant rs11140503 [ dbSNP | Ensembl ].		VAR_039671
	Natural variant	328	1	I → V. Ref.9 Corresponds to variant rs11568418 [ dbSNP | Ensembl ].		VAR_039672
	Natural variant	349	1	R → Q. Ref.9 Corresponds to variant rs45525131 [ dbSNP | Ensembl ].		VAR_039673
	Natural variant	367	1	G → R Reduced transport of inosine and thymidine. Ref.9		VAR_039674
	Natural variant	418	1	L → I. Ref.9		VAR_039675
	Natural variant	513	1	Y → F. Ref.6 Corresponds to variant rs56350726 [ dbSNP | Ensembl ].		VAR_039676
	Natural variant	585	1	R → H. Ref.9		VAR_039677
	Natural variant	602	1	C → R Lower concentrative capacity and altered sodium binding capacity. Ref.10		VAR_039678
Experimental info
	Sequence conflict	628	1	A → S in BAF85538. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9HAS3 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 80FD14518A8BFA61	FASTA	691	76,930
	10 20 30 40 50 60 MELRSTAAPR AEGYSNVGFQ NEENFLENEN TSGNNSIRSR AVQSREHTNT KQDEEQVTVE 70 80 90 100 110 120 QDSPRNREHM EDDDEEMQQK GCLERRYDTV CGFCRKHKTT LRHIIWGILL AGYLVMVISA 130 140 150 160 170 180 CVLNFHRALP LFVITVAAIF FVVWDHLMAK YEHRIDEMLS PGRRLLNSHW FWLKWVIWSS 190 200 210 220 230 240 LVLAVIFWLA FDTAKLGQQQ LVSFGGLIMY IVLLFLFSKY PTRVYWRPVL WGIGLQFLLG 250 260 270 280 290 300 LLILRTDPGF IAFDWLGRQV QTFLEYTDAG ASFVFGEKYK DHFFAFKVLP IVVFFSTVMS 310 320 330 340 350 360 MLYYLGLMQW IIRKVGWIML VTTGSSPIES VVASGNIFVG QTESPLLVRP YLPYITKSEL 370 380 390 400 410 420 HAIMTAGFST IAGSVLGAYI SFGVPSSHLL TASVMSAPAS LAAAKLFWPE TEKPKITLKN 430 440 450 460 470 480 AMKMESGDSG NLLEAATQGA SSSISLVANI AVNLIAFLAL LSFMNSALSW FGNMFDYPQL 490 500 510 520 530 540 SFELICSYIF MPFSFMMGVE WQDSFMVARL IGYKTFFNEF VAYEHLSKWI HLRKEGGPKF 550 560 570 580 590 600 VNGVQQYISI RSEIIATYAL CGFANIGSLG IVIGGLTSMA PSRKRDIASG AVRALIAGTV 610 620 630 640 650 660 ACFMTACIAG ILSSTPVDIN CHHVLENAFN STFPGNTTKV IACCQSLLSS TVAKGPGEVI 670 680 690 PGGNHSLYSL KGCCTLLNPS TFNCNGISNT F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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., Ng A.M.L., Yao S.Y.M., Graham K., Loewen S.K., Smith K.M., Ritzel R.G., Mowles D.A., Carpenter P., Chen X.-Z., Karpinski E., Hyde R.J., Baldwin S.A., Cass C.E., Young J.D. J. Biol. Chem. 276:2914-2927(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[6]	"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." Damaraju S., Zhang J., Visser F., Tackaberry T., Dufour J., Smith K.M., Slugoski M., Ritzel M.W.L., Baldwin S.A., Young J.D., Cass C.E. Pharmacogenet. Genomics 15:173-182(2005) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS ASN-5; PHE-131 AND PHE-513.
[7]	"Electrophysiological characterization and modeling of the structure activity relationship of the human concentrative nucleoside transporter 3 (hCNT3)." Hu H., Endres C.J., Chang C., Umapathy N.S., Lee E.-W., Fei Y.-J., Itagaki S., Swaan P.W., Ganapathy V., Unadkat J.D. Mol. Pharmacol. 69:1542-1553(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters." Yamamoto T., Kuniki K., Takekuma Y., Hirano T., Iseki K., Sugawara M. Eur. J. Pharmacol. 557:1-8(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3)." Badagnani I., Chan W., Castro R.A., Brett C.M., Huang C.C., Stryke D., Kawamoto M., Johns S.J., Ferrin T.E., Carlson E.J., Burchard E.G., Giacomini K.M. Pharmacogenomics J. 5:157-165(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-4; ASN-5; HIS-62; LYS-67; CYS-113; VAL-328; GLN-349; ARG-367; ILE-418 AND HIS-585, CHARACTERIZATION OF VARIANT ARG-367.
[10]	"Functional characterization of a nucleoside-derived drug transporter variant (hCNT3C602R) showing altered sodium-binding capacity." Errasti-Murugarren E., Cano-Soldado P., Pastor-Anglada M., Casado F.J. Mol. Pharmacol. 73:379-386(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-602, CHARACTERIZATION OF VARIANT ARG-602.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF305210 mRNA. Translation: AAG22551.1. AK292849 mRNA. Translation: BAF85538.1. AL356134, AL353787 Genomic DNA. Translation: CAH73162.1. AL353787, AL356134 Genomic DNA. Translation: CAI16332.1. BC093821 mRNA. Translation: AAH93821.1. BC093823 mRNA. Translation: AAH93823.1. CH471089 Genomic DNA. Translation: EAW62686.1.
IPI	IPI00005485.
RefSeq	NP_001186562.1. NM_001199633.1. NP_071410.1. NM_022127.2.
UniGene	Hs.535966.
3D structure databases
ProteinModelPortal	Q9HAS3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000365413.
PTM databases
PhosphoSite	Q9HAS3.
Polymorphism databases
DMDM	74752767.
Proteomic databases
PaxDb	Q9HAS3.
PRIDE	Q9HAS3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376238; ENSP00000365413; ENSG00000197506.
GeneID	64078.
KEGG	hsa:64078.
UCSC	uc004anu.2. human.
Organism-specific databases
CTD	64078.
GeneCards	GC09M086890.
HGNC	HGNC:16484. SLC28A3.
HPA	HPA023311. HPA024729.
MIM	608269. gene.
neXtProt	NX_Q9HAS3.
PharmGKB	PA426.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1972.
HOGENOM	HOG000267658.
HOVERGEN	HBG054073.
InParanoid	Q9HAS3.
KO	K11536.
OMA	TRVYWRP.
OrthoDB	EOG4VT5X8.
PhylomeDB	Q9HAS3.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9HAS3.
Bgee	Q9HAS3.
CleanEx	HS_SLC28A3.
Genevestigator	Q9HAS3.
Family and domain databases
InterPro	IPR008276. C_nuclsd_transpt. IPR018270. C_nuclsd_transpt_met_bac. IPR011657. Nucleos_tra2_C. IPR011642. Nucleoside_recog_Gate. IPR002668. Nuclsd_transpt2. [Graphical view]
PANTHER	PTHR10590. PTHR10590. 1 hit.
Pfam	PF07670. Gate. 1 hit. PF07662. Nucleos_tra2_C. 1 hit. PF01773. Nucleos_tra2_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR00804. nupC. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q9HAS3.
ChEMBL	CHEMBL5707.
GenomeRNAi	64078.
NextBio	65862.
SOURCE	Search...

Entry information

Entry name

S28A3_HUMAN

Accession

Primary (citable) accession number: Q9HAS3
Secondary accession number(s): A8K9Y4, B1AML0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	March 1, 2001
Last modified:	April 3, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.