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Protein

Sodium/nucleoside cotransporter 1

Gene

SLC28A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine). It also transports the antiviral pyrimidine nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immunodeficiency syndrome (AIDS). It has the following selective inhibition: adenosine, thymidine, cytidine, uridine >> guanosine, inosine.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processTransport

Enzyme and pathway databases

ReactomeiR-HSA-83936 Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane

Protein family/group databases

TCDBi2.A.41.2.3 the concentrative nucleoside transporter (cnt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/nucleoside cotransporter 1
Alternative name(s):
Concentrative nucleoside transporter 1
Short name:
CNT 1
Short name:
hCNT1
Na(+)/nucleoside cotransporter 1
Sodium-coupled nucleoside transporter 1
Solute carrier family 28 member 1
Gene namesi
Name:SLC28A1
Synonyms:CNT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000156222.11
HGNCiHGNC:11001 SLC28A1
MIMi606207 gene
neXtProtiNX_O00337

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 80CytoplasmicSequence analysisAdd BLAST80
Transmembranei81 – 104HelicalSequence analysisAdd BLAST24
Topological domaini105 – 109ExtracellularSequence analysis5
Transmembranei110 – 128HelicalSequence analysisAdd BLAST19
Topological domaini129 – 147CytoplasmicSequence analysisAdd BLAST19
Transmembranei148 – 167HelicalSequence analysisAdd BLAST20
Topological domaini168 – 178ExtracellularSequence analysisAdd BLAST11
Transmembranei179 – 195HelicalSequence analysisAdd BLAST17
Topological domaini196 – 201CytoplasmicSequence analysis6
Transmembranei202 – 222HelicalSequence analysisAdd BLAST21
Topological domaini223 – 261ExtracellularSequence analysisAdd BLAST39
Transmembranei262 – 283HelicalSequence analysisAdd BLAST22
Topological domaini284 – 294CytoplasmicSequence analysisAdd BLAST11
Transmembranei295 – 318HelicalSequence analysisAdd BLAST24
Topological domaini319 – 337ExtracellularSequence analysisAdd BLAST19
Transmembranei338 – 360HelicalSequence analysisAdd BLAST23
Topological domaini361 – 366CytoplasmicSequence analysis6
Transmembranei367 – 386HelicalSequence analysisAdd BLAST20
Topological domaini387 – 423ExtracellularSequence analysisAdd BLAST37
Transmembranei424 – 446HelicalSequence analysisAdd BLAST23
Topological domaini447 – 457CytoplasmicSequence analysisAdd BLAST11
Transmembranei458 – 479HelicalSequence analysisAdd BLAST22
Topological domaini480 – 534ExtracellularSequence analysisAdd BLAST55
Transmembranei535 – 558HelicalSequence analysisAdd BLAST24
Topological domaini559 – 569CytoplasmicSequence analysisAdd BLAST11
Transmembranei570 – 592HelicalSequence analysisAdd BLAST23
Topological domaini593 – 649ExtracellularSequence analysisAdd BLAST57

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi318S → G: Enables transport of purine nucleosides. 1 Publication1
Mutagenesisi319Q → M: Increases transport of purine nucleosides; when associated with Gly-319. 1 Publication1
Mutagenesisi352S → T: Produces a full purine-type transporter; when associated with Gly-319 and Met-320. 1 Publication1

Organism-specific databases

DisGeNETi9154
OpenTargetsiENSG00000156222
PharmGKBiPA387

Chemistry databases

ChEMBLiCHEMBL5551
DrugBankiDB00441 Gemcitabine
DB00649 Stavudine
DB00495 Zidovudine

Polymorphism and mutation databases

BioMutaiSLC28A1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000704461 – 649Sodium/nucleoside cotransporter 1Add BLAST649

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi605N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi643N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO00337
PaxDbiO00337
PeptideAtlasiO00337
PRIDEiO00337
ProteomicsDBi47852
47853 [O00337-2]

PTM databases

iPTMnetiO00337
PhosphoSitePlusiO00337

Expressioni

Tissue specificityi

Expressed in kidney.

Gene expression databases

BgeeiENSG00000156222 Expressed in 79 organ(s), highest expression level in right lobe of liver
CleanExiHS_SLC28A1
ExpressionAtlasiO00337 baseline and differential
GenevisibleiO00337 HS

Organism-specific databases

HPAiHPA019551

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000286749

Chemistry databases

BindingDBiO00337

Structurei

3D structure databases

ProteinModelPortaliO00337
SMRiO00337
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi609 – 612Poly-Ser4

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3747 Eukaryota
COG1972 LUCA
GeneTreeiENSGT00390000016025
HOVERGENiHBG054073
InParanoidiO00337
KOiK11536
OMAiHRWIVQT
OrthoDBiEOG091G05D5
PhylomeDBiO00337
TreeFamiTF314131

Family and domain databases

InterProiView protein in InterPro
IPR008276 C_nuclsd_transpt
IPR018270 C_nuclsd_transpt_met_bac
IPR030212 CNT1/CNT2
IPR011657 CNT_C_dom
IPR002668 CNT_N_dom
IPR011642 Gate_dom
PANTHERiPTHR10590 PTHR10590, 1 hit
PTHR10590:SF16 PTHR10590:SF16, 1 hit
PfamiView protein in Pfam
PF07670 Gate, 1 hit
PF07662 Nucleos_tra2_C, 1 hit
PF01773 Nucleos_tra2_N, 1 hit
TIGRFAMsiTIGR00804 nupC, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O00337-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MENDPSRRRE SISLTPVAKG LENMGADFLE SLEEGQLPRS DLSPAEIRSS
60 70 80 90 100
WSEAAPKPFS RWRNLQPALR ARSFCREHMQ LFRWIGTGLL CTGLSAFLLV
110 120 130 140 150
ACLLDFQRAL ALFVLTCVVL TFLGHRLLKR LLGPKLRRFL KPQGHPRLLL
160 170 180 190 200
WFKRGLALAA FLGLVLWLSL DTSQRPEQLV SFAGICVFVA LLFACSKHHC
210 220 230 240 250
AVSWRAVSWG LGLQFVLGLL VIRTEPGFIA FEWLGEQIRI FLSYTKAGSS
260 270 280 290 300
FVFGEALVKD VFAFQVLPII VFFSCVISVL YHVGLMQWVI LKIAWLMQVT
310 320 330 340 350
MGTTATETLS VAGNIFVSQT EAPLLIRPYL ADMTLSEVHV VMTGGYATIA
360 370 380 390 400
GSLLGAYISF GIDATSLIAA SVMAAPCALA LSKLVYPEVE ESKFRREEGV
410 420 430 440 450
KLTYGDAQNL IEAASTGAAI SVKVVANIAA NLIAFLAVLD FINAALSWLG
460 470 480 490 500
DMVDIQGLSF QLICSYILRP VAFLMGVAWE DCPVVAELLG IKLFLNEFVA
510 520 530 540 550
YQDLSKYKQR RLAGAEEWVG DRKQWISVRA EVLTTFALCG FANFSSIGIM
560 570 580 590 600
LGGLTSMVPQ RKSDFSQIVL RALFTGACVS LVNACMAGIL YMPRGAEVDC
610 620 630 640
MSLLNTTLSS SSFEIYQCCR EAFQSVNPEF SPEALDNCCR FYNHTICAQ
Length:649
Mass (Da):71,584
Last modified:May 5, 2009 - v2
Checksum:i42E952443B46B102
GO
Isoform 2 (identifier: O00337-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     155-175: GLALAAFLGLVLWLSLDTSQR → DPRPWSKEGPNQYLPQITWTV
     176-649: Missing.

Show »
Length:175
Mass (Da):20,180
Checksum:i34C7DD93D84F60EE
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7Z3L6B7Z3L6_HUMAN
cDNA FLJ58165, highly similar to So...
SLC28A1
483Annotation score:

Polymorphismi

Three variant forms of isoform 1 (A, B and C) are expressed in the kidney. All three variant forms have similar nucleoside transport activity.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00949934E → G in allele A. 2 Publications1
Natural variantiVAR_009500140L → LV in allele A. 2 Publications1
Natural variantiVAR_009501189V → I in allele A. 2 PublicationsCorresponds to variant dbSNP:rs2290272Ensembl.1
Natural variantiVAR_057194190A → S. Corresponds to variant dbSNP:rs45523532Ensembl.1
Natural variantiVAR_057195237Q → K. Corresponds to variant dbSNP:rs8187758Ensembl.1
Natural variantiVAR_009502409N → S in allele B. 1 Publication1
Natural variantiVAR_057196510R → C1 PublicationCorresponds to variant dbSNP:rs2242047Ensembl.1
Natural variantiVAR_009503521D → N in alleles B and C. 2 PublicationsCorresponds to variant dbSNP:rs2242046Ensembl.1
Natural variantiVAR_061802546S → P. Corresponds to variant dbSNP:rs45584739Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037221155 – 175GLALA…DTSQR → DPRPWSKEGPNQYLPQITWT V in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_037222176 – 649Missing in isoform 2. 1 PublicationAdd BLAST474

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62966 mRNA Translation: AAB53837.1
U62967 mRNA Translation: AAB53838.1
U62968 mRNA Translation: AAB53839.1
AF187978
, AF187969, AF187970, AF187971, AF187972, AF187973, AF187974, AF187975, AF187976, AF187977 Genomic DNA Translation: AAF15353.1
AK291997 mRNA Translation: BAF84686.1
AC087468 Genomic DNA No translation available.
AC103741 Genomic DNA No translation available.
BC029788 mRNA Translation: AAH29788.1
BC039898 mRNA Translation: AAH39898.1
BC126204 mRNA Translation: AAI26205.1
BC126206 mRNA Translation: AAI26207.1
CCDSiCCDS10334.1 [O00337-1]
CCDS10335.1 [O00337-2]
RefSeqiNP_001274691.1, NM_001287762.1 [O00337-1]
NP_004204.3, NM_004213.4 [O00337-1]
NP_964014.1, NM_201651.2 [O00337-2]
UniGeneiHs.459187

Genome annotation databases

EnsembliENST00000286749; ENSP00000286749; ENSG00000156222 [O00337-1]
ENST00000338602; ENSP00000341629; ENSG00000156222 [O00337-2]
ENST00000394573; ENSP00000378074; ENSG00000156222 [O00337-1]
GeneIDi9154
KEGGihsa:9154
UCSCiuc002blf.5 human [O00337-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U62966 mRNA Translation: AAB53837.1
U62967 mRNA Translation: AAB53838.1
U62968 mRNA Translation: AAB53839.1
AF187978
, AF187969, AF187970, AF187971, AF187972, AF187973, AF187974, AF187975, AF187976, AF187977 Genomic DNA Translation: AAF15353.1
AK291997 mRNA Translation: BAF84686.1
AC087468 Genomic DNA No translation available.
AC103741 Genomic DNA No translation available.
BC029788 mRNA Translation: AAH29788.1
BC039898 mRNA Translation: AAH39898.1
BC126204 mRNA Translation: AAI26205.1
BC126206 mRNA Translation: AAI26207.1
CCDSiCCDS10334.1 [O00337-1]
CCDS10335.1 [O00337-2]
RefSeqiNP_001274691.1, NM_001287762.1 [O00337-1]
NP_004204.3, NM_004213.4 [O00337-1]
NP_964014.1, NM_201651.2 [O00337-2]
UniGeneiHs.459187

3D structure databases

ProteinModelPortaliO00337
SMRiO00337
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000286749

Chemistry databases

BindingDBiO00337
ChEMBLiCHEMBL5551
DrugBankiDB00441 Gemcitabine
DB00649 Stavudine
DB00495 Zidovudine

Protein family/group databases

TCDBi2.A.41.2.3 the concentrative nucleoside transporter (cnt) family

PTM databases

iPTMnetiO00337
PhosphoSitePlusiO00337

Polymorphism and mutation databases

BioMutaiSLC28A1

Proteomic databases

EPDiO00337
PaxDbiO00337
PeptideAtlasiO00337
PRIDEiO00337
ProteomicsDBi47852
47853 [O00337-2]

Protocols and materials databases

DNASUi9154
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286749; ENSP00000286749; ENSG00000156222 [O00337-1]
ENST00000338602; ENSP00000341629; ENSG00000156222 [O00337-2]
ENST00000394573; ENSP00000378074; ENSG00000156222 [O00337-1]
GeneIDi9154
KEGGihsa:9154
UCSCiuc002blf.5 human [O00337-1]

Organism-specific databases

CTDi9154
DisGeNETi9154
EuPathDBiHostDB:ENSG00000156222.11
GeneCardsiSLC28A1
HGNCiHGNC:11001 SLC28A1
HPAiHPA019551
MIMi606207 gene
neXtProtiNX_O00337
OpenTargetsiENSG00000156222
PharmGKBiPA387
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3747 Eukaryota
COG1972 LUCA
GeneTreeiENSGT00390000016025
HOVERGENiHBG054073
InParanoidiO00337
KOiK11536
OMAiHRWIVQT
OrthoDBiEOG091G05D5
PhylomeDBiO00337
TreeFamiTF314131

Enzyme and pathway databases

ReactomeiR-HSA-83936 Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane

Miscellaneous databases

ChiTaRSiSLC28A1 human
GeneWikiiConcentrative_nucleoside_transporter_1
GenomeRNAii9154
PROiPR:O00337
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156222 Expressed in 79 organ(s), highest expression level in right lobe of liver
CleanExiHS_SLC28A1
ExpressionAtlasiO00337 baseline and differential
GenevisibleiO00337 HS

Family and domain databases

InterProiView protein in InterPro
IPR008276 C_nuclsd_transpt
IPR018270 C_nuclsd_transpt_met_bac
IPR030212 CNT1/CNT2
IPR011657 CNT_C_dom
IPR002668 CNT_N_dom
IPR011642 Gate_dom
PANTHERiPTHR10590 PTHR10590, 1 hit
PTHR10590:SF16 PTHR10590:SF16, 1 hit
PfamiView protein in Pfam
PF07670 Gate, 1 hit
PF07662 Nucleos_tra2_C, 1 hit
PF01773 Nucleos_tra2_N, 1 hit
TIGRFAMsiTIGR00804 nupC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiS28A1_HUMAN
AccessioniPrimary (citable) accession number: O00337
Secondary accession number(s): A0AV42
, A8K7I2, O00335, O00336, Q5U5S6, Q5U648, Q9UEZ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 5, 2009
Last modified: November 7, 2018
This is version 156 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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