O43868 (S28A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/nucleoside cotransporter 2

Alternative name(s):
Concentrative nucleoside transporter 2
Short name=CNT 2
Short name=hCNT2
Na(+)/nucleoside cotransporter 2
Sodium-coupled nucleoside transporter 2
Sodium/purine nucleoside co-transporter
Short name=SPNT
Solute carrier family 28 member 2

Gene names

Name:	SLC28A2
Synonyms:	CNT2

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	658 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Sodium-dependent and purine-selective transporter. Exhibits the transport characteristics of the nucleoside transport system cif or N1 subtype (N1/cif) (selective for purine nucleosides and uridine). Plays a critical role in specific uptake and salvage of purine nucleosides in kidney and other tissues.
Enzyme regulation	Inhibited by formycin B.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in heart and skeletal muscle followed by liver, kidney, intestine, pancreas, placenta and brain. Weak expression in lung.
Sequence similarities	Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family. [View classification]

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleobase-containing compound metabolic process Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	nucleoside binding Inferred from electronic annotation. Source: InterPro nucleoside:sodium symporter activity Inferred from electronic annotation. Source: InterPro purine nucleoside transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 658	658	Sodium/nucleoside cotransporter 2		PRO_0000070450
Regions
	Transmembrane	80 – 100	21	Helical; Potential
	Transmembrane	104 – 123	20	Helical; Potential
	Transmembrane	148 – 166	19	Helical; Potential
	Transmembrane	172 – 192	21	Helical; Potential
	Transmembrane	200 – 220	21	Helical; Potential
	Transmembrane	233 – 253	21	Helical; Potential
	Transmembrane	260 – 280	21	Helical; Potential
	Transmembrane	295 – 314	20	Helical; Potential
	Transmembrane	336 – 355	20	Helical; Potential
	Transmembrane	362 – 381	20	Helical; Potential
	Transmembrane	423 – 443	21	Helical; Potential
	Transmembrane	454 – 474	21	Helical; Potential
	Transmembrane	529 – 549	21	Helical; Potential
	Transmembrane	567 – 587	21	Helical; Potential
Natural variations
	Natural variant	12	1	L → P. Ref.7		VAR_036817
	Natural variant	22	1	P → L. Ref.6 Ref.7 Corresponds to variant rs11854484 [ dbSNP | Ensembl ].		VAR_024639
	Natural variant	75	1	S → R. Ref.2 Ref.6 Ref.7 Corresponds to variant rs1060896 [ dbSNP | Ensembl ].		VAR_024640
	Natural variant	142	1	R → H. Ref.7		VAR_036818
	Natural variant	163	1	L → W. Ref.6 Ref.7 Corresponds to variant rs2271437 [ dbSNP | Ensembl ].		VAR_022001
	Natural variant	172	1	E → D. Ref.7		VAR_036819
	Natural variant	245	1	S → T. Ref.6 Corresponds to variant rs10519020 [ dbSNP | Ensembl ].		VAR_024641
	Natural variant	355	1	F → S. Ref.6 Corresponds to variant rs17215633 [ dbSNP | Ensembl ].		VAR_024642
	Natural variant	385	1	E → K. Ref.7		VAR_036820
	Natural variant	462	1	L → F. Ref.6		VAR_024643
	Natural variant	509	1	G → E. Corresponds to variant rs9635306 [ dbSNP | Ensembl ].		VAR_028724
	Natural variant	612	1	M → T. Ref.7		VAR_036821

Sequences

	Sequence		Length	Mass (Da)
	O43868 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 273545EE75E0D663	FASTA	658	71,926
	10 20 30 40 50 60 MEKASGRQSI ALSTVETGTV NPGLELMEKE VEPEGSKRTD AQGHSLGDGL GPSTYQRRSR 70 80 90 100 110 120 WPFSKARSFC KTHASLFKKI LLGLLCLAYA AYLLAACILN FQRALALFVI TCLVIFVLVH 130 140 150 160 170 180 SFLKKLLGKK LTRCLKPFEN SRLRLWTKWV FAGVSLVGLI LWLALDTAQR PEQLIPFAGI 190 200 210 220 230 240 CMFILILFAC SKHHSAVSWR TVFSGLGLQF VFGILVIRTD LGYTVFQWLG EQVQIFLNYT 250 260 270 280 290 300 VAGSSFVFGD TLVKDVFAFQ ALPIIIFFGC VVSILYYLGL VQWVVQKVAW FLQITMGTTA 310 320 330 340 350 360 TETLAVAGNI FVGMTEAPLL IRPYLGDMTL SEIHAVMTGG FATISGTVLG AFIAFGVDAS 370 380 390 400 410 420 SLISASVMAA PCALASSKLA YPEVEESKFK SEEGVKLPRG KERNVLEAAS NGAVDAIGLA 430 440 450 460 470 480 TNVAANLIAF LAVLAFINAA LSWLGELVDI QGLTFQVICS YLLRPMVFMM GVEWTDCPMV 490 500 510 520 530 540 AEMVGIKFFI NEFVAYQQLS QYKNKRLSGM EEWIEGEKQW ISVRAEIITT FSLCGFANLS 550 560 570 580 590 600 SIGITLGGLT SIVPHRKSDL SKVVVRALFT GACVSLISAC MAGILYVPRG AEADCVSFPN 610 620 630 640 650 TSFTNRTYET YMCCRGLFQS TSLNGTNPPS FSGPWEDKEF SAMALTNCCG FYNNTVCA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Na+-dependent purine nucleoside transporter from human kidney: cloning and functional characterization." Wang J., Su S.-F., Dresser M.J., Schaner M.E., Washington C.B., Giacomini K.M. Am. J. Physiol. 273:F1058-F1065(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine." Ritzel M.W.L., Yao S.Y.M., Ng A.M.L., Mackey J.R., Cass C.E., Young J.D. Mol. Membr. Biol. 15:203-211(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-75. Tissue: Small intestine.
[3]	"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: Small intestine.
[4]	"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.
[5]	"Identification of amino acid residues responsible for the pyrimidine and purine nucleoside specificities of human concentrative Na(+) nucleoside cotransporters hCNT1 and hCNT2." Loewen S.K., Ng A.M.L., Yao S.Y.M., Cass C.E., Baldwin S.A., Young J.D. J. Biol. Chem. 274:24475-24484(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[6]	"Genetic analysis and functional characterization of polymorphisms in the human concentrative nucleoside transporter, CNT2." Owen R.P., Gray J.H., Taylor T.R., Carlson E.J., Huang C.C., Kawamoto M., Johns S.J., Stryke D., Ferrin T.E., Giacomini K.M. Pharmacogenet. Genomics 15:83-90(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LEU-22; ARG-75; TRP-163; THR-245; SER-355 AND PHE-462.
[7]	"Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians." Li L., Tan C.M.F., Koo S.H., Chong K.T., Lee E.J.D. Pharmacogenet. Genomics 17:783-786(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PRO-12; LEU-22; ARG-75; HIS-142; TRP-163; ASP-172; LYS-385 AND THR-612.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U84392 mRNA. Translation: AAC51930.1. AF036109 mRNA. Translation: AAB88539.1. AK291974 mRNA. Translation: BAF84663.1. BC093737 mRNA. Translation: AAH93737.1.
IPI	IPI00014561.
RefSeq	NP_004203.2. NM_004212.3.
UniGene	Hs.367833.
3D structure databases
ProteinModelPortal	O43868.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000315006.
Protein family/group databases
TCDB	2.A.41.2.4. concentrative nucleoside transporter (CNT) family.
PTM databases
PhosphoSite	O43868.
Proteomic databases
PaxDb	O43868.
PRIDE	O43868.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000347644; ENSP00000315006; ENSG00000137860.
GeneID	9153.
KEGG	hsa:9153.
UCSC	uc001zva.2. human.
Organism-specific databases
CTD	9153.
GeneCards	GC15P045544.
HGNC	HGNC:11002. SLC28A2.
MIM	606208. gene.
neXtProt	NX_O43868.
PharmGKB	PA386.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1972.
HOGENOM	HOG000267658.
HOVERGEN	HBG054073.
InParanoid	O43868.
KO	K11536.
OMA	IMQWIIR.
OrthoDB	EOG4V170B.
PhylomeDB	O43868.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O43868.
Bgee	O43868.
CleanEx	HS_SLC28A2.
Genevestigator	O43868.
GermOnline	ENSG00000137860. Homo sapiens.
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	O43868.
ChEMBL	CHEMBL5780.
GenomeRNAi	9153.
NextBio	34339.
SOURCE	Search...

Entry information

Entry name

S28A2_HUMAN

Accession

Primary (citable) accession number: O43868
Secondary accession number(s): A8K7F9, O43239, Q52LZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	October 17, 2006
Last modified:	April 3, 2013
This is version 116 of the entry and version 2 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.