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Protein

Solute carrier family 28 member 3

Gene

SLC28A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Kineticsi

  1. KM=21.6 µM for uridine2 Publications
  2. KM=15.4 µM for cytidine2 Publications
  3. KM=21.2 µM for thymidine2 Publications
  4. KM=15.1 µM for adenosine2 Publications
  5. KM=43 µM for guanosine2 Publications
  6. KM=52.5 µM for inosine2 Publications
  1. Vmax=25.8 pmol/min/mg enzyme for uridine uptake2 Publications
  2. Vmax=32.8 pmol/min/mg enzyme for cytidine uptake2 Publications
  3. Vmax=24.2 pmol/min/mg enzyme for thymidine uptake2 Publications
  4. Vmax=30.4 pmol/min/mg enzyme for adenosine uptake2 Publications
  5. Vmax=51.4 pmol/min/mg enzyme for guanosine uptake2 Publications
  6. Vmax=44.8 pmol/min/mg enzyme for inosine uptake2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:G66-31706-MONOMER.
ReactomeiR-HSA-83936. Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.

Protein family/group databases

TCDBi2.A.41.2.8. the concentrative nucleoside transporter (cnt) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 28 member 3
Alternative name(s):
Concentrative Na(+)-nucleoside cotransporter 3
Short name:
CNT 3
Short name:
hCNT3
Gene namesi
Name:SLC28A3
Synonyms:CNT3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:16484. SLC28A3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 102CytoplasmicSequence analysisAdd BLAST102
Transmembranei103 – 123HelicalSequence analysisAdd BLAST21
Topological domaini124 – 127ExtracellularSequence analysis4
Transmembranei128 – 148HelicalSequence analysisAdd BLAST21
Topological domaini149 – 170CytoplasmicSequence analysisAdd BLAST22
Transmembranei171 – 191HelicalSequence analysisAdd BLAST21
Topological domaini192 – 200ExtracellularSequence analysis9
Transmembranei201 – 221HelicalSequence analysisAdd BLAST21
Topological domaini222 – 223CytoplasmicSequence analysis2
Transmembranei224 – 244HelicalSequence analysisAdd BLAST21
Topological domaini245 – 287ExtracellularSequence analysisAdd BLAST43
Transmembranei288 – 308HelicalSequence analysisAdd BLAST21
Topological domaini309 – 314CytoplasmicSequence analysis6
Transmembranei315 – 335HelicalSequence analysisAdd BLAST21
Topological domaini336 – 361ExtracellularSequence analysisAdd BLAST26
Transmembranei362 – 382HelicalSequence analysisAdd BLAST21
Topological domaini383 – 388CytoplasmicSequence analysis6
Transmembranei389 – 409HelicalSequence analysisAdd BLAST21
Topological domaini410 – 443ExtracellularSequence analysisAdd BLAST34
Transmembranei444 – 464HelicalSequence analysisAdd BLAST21
Topological domaini465 – 479CytoplasmicSequence analysisAdd BLAST15
Transmembranei480 – 500HelicalSequence analysisAdd BLAST21
Topological domaini501 – 553ExtracellularSequence analysisAdd BLAST53
Transmembranei554 – 574HelicalSequence analysisAdd BLAST21
Topological domaini575 – 593CytoplasmicSequence analysisAdd BLAST19
Transmembranei594 – 614HelicalSequence analysisAdd BLAST21
Topological domaini615 – 691ExtracellularSequence analysisAdd BLAST77

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi64078.
OpenTargetsiENSG00000197506.
PharmGKBiPA426.

Chemistry databases

ChEMBLiCHEMBL5707.
DrugBankiDB00640. Adenosine.
DB00242. Cladribine.
DB01073. Fludarabine.
DB00441. Gemcitabine.
DB01033. Mercaptopurine.
DB00811. Ribavirin.
GuidetoPHARMACOLOGYi1116.

Polymorphism and mutation databases

BioMutaiSLC28A3.
DMDMi74752767.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003241461 – 691Solute carrier family 28 member 3Add BLAST691

Proteomic databases

EPDiQ9HAS3.
PaxDbiQ9HAS3.
PeptideAtlasiQ9HAS3.
PRIDEiQ9HAS3.

PTM databases

iPTMnetiQ9HAS3.
PhosphoSitePlusiQ9HAS3.

Expressioni

Tissue specificityi

Expressed in pancreas, bone marrow, trachea, mammary gland, liver, prostate, and regions of intestine, brain, lung, placenta, testis, kidney, and heart.1 Publication

Inductioni

Up-regulated by phorbol myristate acetate (PMA) in HL-60 cells.1 Publication

Gene expression databases

BgeeiENSG00000197506.
CleanExiHS_SLC28A3.
GenevisibleiQ9HAS3. HS.

Organism-specific databases

HPAiHPA023311.
HPA024729.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000365413.

Chemistry databases

BindingDBiQ9HAS3.

Structurei

3D structure databases

ProteinModelPortaliQ9HAS3.
SMRiQ9HAS3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3747. Eukaryota.
COG1972. LUCA.
GeneTreeiENSGT00390000016025.
HOGENOMiHOG000267658.
HOVERGENiHBG054073.
InParanoidiQ9HAS3.
KOiK11536.
OMAiGCCTLLN.
OrthoDBiEOG091G05D5.
PhylomeDBiQ9HAS3.
TreeFamiTF314131.

Family and domain databases

InterProiIPR008276. C_nuclsd_transpt.
IPR018270. C_nuclsd_transpt_met_bac.
IPR030211. CNT3.
IPR011657. CNT_C_dom.
IPR002668. CNT_N_dom.
IPR011642. Gate_dom.
[Graphical view]
PANTHERiPTHR10590. PTHR10590. 1 hit.
PTHR10590:SF18. PTHR10590:SF18. 1 hit.
PfamiPF07670. Gate. 1 hit.
PF07662. Nucleos_tra2_C. 1 hit.
PF01773. Nucleos_tra2_N. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00804. nupC. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9HAS3-1) [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
MELRSTAAPR AEGYSNVGFQ NEENFLENEN TSGNNSIRSR AVQSREHTNT
60 70 80 90 100
KQDEEQVTVE QDSPRNREHM EDDDEEMQQK GCLERRYDTV CGFCRKHKTT
110 120 130 140 150
LRHIIWGILL AGYLVMVISA CVLNFHRALP LFVITVAAIF FVVWDHLMAK
160 170 180 190 200
YEHRIDEMLS PGRRLLNSHW FWLKWVIWSS LVLAVIFWLA FDTAKLGQQQ
210 220 230 240 250
LVSFGGLIMY IVLLFLFSKY PTRVYWRPVL WGIGLQFLLG LLILRTDPGF
260 270 280 290 300
IAFDWLGRQV QTFLEYTDAG ASFVFGEKYK DHFFAFKVLP IVVFFSTVMS
310 320 330 340 350
MLYYLGLMQW IIRKVGWIML VTTGSSPIES VVASGNIFVG QTESPLLVRP
360 370 380 390 400
YLPYITKSEL HAIMTAGFST IAGSVLGAYI SFGVPSSHLL TASVMSAPAS
410 420 430 440 450
LAAAKLFWPE TEKPKITLKN AMKMESGDSG NLLEAATQGA SSSISLVANI
460 470 480 490 500
AVNLIAFLAL LSFMNSALSW FGNMFDYPQL SFELICSYIF MPFSFMMGVE
510 520 530 540 550
WQDSFMVARL IGYKTFFNEF VAYEHLSKWI HLRKEGGPKF VNGVQQYISI
560 570 580 590 600
RSEIIATYAL CGFANIGSLG IVIGGLTSMA PSRKRDIASG AVRALIAGTV
610 620 630 640 650
ACFMTACIAG ILSSTPVDIN CHHVLENAFN STFPGNTTKV IACCQSLLSS
660 670 680 690
TVAKGPGEVI PGGNHSLYSL KGCCTLLNPS TFNCNGISNT F
Length:691
Mass (Da):76,930
Last modified:March 1, 2001 - v1
Checksum:i80FD14518A8BFA61
GO
Isoform 2 (identifier: Q9HAS3-2) [UniParc]FASTAAdd to basket
Also known as: hCNT3ins

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.

Note: Exhibits a shorter half-life than isoform 1, degraded via a proteasome-dependent pathway.
Show »
Length:622
Mass (Da):69,027
Checksum:i8C9CB6F47D0AC0C0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti251I → V in BAG36748 (PubMed:14702039).Curated1
Sequence conflicti293V → I in BAG36748 (PubMed:14702039).Curated1
Sequence conflicti505F → L in BAG65240 (PubMed:14702039).Curated1
Sequence conflicti628A → S in BAF85538 (PubMed:14702039).Curated1
Sequence conflicti639K → E in BAG36748 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0396654R → K.1 PublicationCorresponds to variant rs11568401dbSNPEnsembl.1
Natural variantiVAR_0396665S → N.2 PublicationsCorresponds to variant rs11568403dbSNPEnsembl.1
Natural variantiVAR_03966762D → H.1 PublicationCorresponds to variant rs45621433dbSNPEnsembl.1
Natural variantiVAR_03966867R → K.1 PublicationCorresponds to variant rs11568411dbSNPEnsembl.1
Natural variantiVAR_039669113Y → C.2 PublicationsCorresponds to variant rs10868138dbSNPEnsembl.1
Natural variantiVAR_039670131L → F.1 Publication1
Natural variantiVAR_039671221P → Q.Corresponds to variant rs11140503dbSNPEnsembl.1
Natural variantiVAR_039672328I → V.1 PublicationCorresponds to variant rs11568418dbSNPEnsembl.1
Natural variantiVAR_039673349R → Q.1 PublicationCorresponds to variant rs45525131dbSNPEnsembl.1
Natural variantiVAR_070606366A → T.1 PublicationCorresponds to variant rs140138960dbSNPEnsembl.1
Natural variantiVAR_039674367G → R Reduced transport of inosine and thymidine. 1 PublicationCorresponds to variant rs11568388dbSNPEnsembl.1
Natural variantiVAR_039675418L → I.1 PublicationCorresponds to variant rs11568405dbSNPEnsembl.1
Natural variantiVAR_039676513Y → F.2 PublicationsCorresponds to variant rs56350726dbSNPEnsembl.1
Natural variantiVAR_039677585R → H.1 PublicationCorresponds to variant rs11568398dbSNPEnsembl.1
Natural variantiVAR_039678602C → R Lower concentrative capacity and altered sodium binding capacity. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0538481 – 69Missing in isoform 2. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305210 mRNA. Translation: AAG22551.1.
AK292849 mRNA. Translation: BAF85538.1.
AK304406 mRNA. Translation: BAG65240.1.
AK314039 mRNA. Translation: BAG36748.1.
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.
CCDSiCCDS6670.1. [Q9HAS3-1]
RefSeqiNP_001186562.1. NM_001199633.1. [Q9HAS3-1]
NP_071410.1. NM_022127.2. [Q9HAS3-1]
UniGeneiHs.535966.

Genome annotation databases

EnsembliENST00000376238; ENSP00000365413; ENSG00000197506. [Q9HAS3-1]
GeneIDi64078.
KEGGihsa:64078.
UCSCiuc010mpz.4. human. [Q9HAS3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305210 mRNA. Translation: AAG22551.1.
AK292849 mRNA. Translation: BAF85538.1.
AK304406 mRNA. Translation: BAG65240.1.
AK314039 mRNA. Translation: BAG36748.1.
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.
CCDSiCCDS6670.1. [Q9HAS3-1]
RefSeqiNP_001186562.1. NM_001199633.1. [Q9HAS3-1]
NP_071410.1. NM_022127.2. [Q9HAS3-1]
UniGeneiHs.535966.

3D structure databases

ProteinModelPortaliQ9HAS3.
SMRiQ9HAS3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000365413.

Chemistry databases

BindingDBiQ9HAS3.
ChEMBLiCHEMBL5707.
DrugBankiDB00640. Adenosine.
DB00242. Cladribine.
DB01073. Fludarabine.
DB00441. Gemcitabine.
DB01033. Mercaptopurine.
DB00811. Ribavirin.
GuidetoPHARMACOLOGYi1116.

Protein family/group databases

TCDBi2.A.41.2.8. the concentrative nucleoside transporter (cnt) family.

PTM databases

iPTMnetiQ9HAS3.
PhosphoSitePlusiQ9HAS3.

Polymorphism and mutation databases

BioMutaiSLC28A3.
DMDMi74752767.

Proteomic databases

EPDiQ9HAS3.
PaxDbiQ9HAS3.
PeptideAtlasiQ9HAS3.
PRIDEiQ9HAS3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376238; ENSP00000365413; ENSG00000197506. [Q9HAS3-1]
GeneIDi64078.
KEGGihsa:64078.
UCSCiuc010mpz.4. human. [Q9HAS3-1]

Organism-specific databases

CTDi64078.
DisGeNETi64078.
GeneCardsiSLC28A3.
HGNCiHGNC:16484. SLC28A3.
HPAiHPA023311.
HPA024729.
MIMi608269. gene.
neXtProtiNX_Q9HAS3.
OpenTargetsiENSG00000197506.
PharmGKBiPA426.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3747. Eukaryota.
COG1972. LUCA.
GeneTreeiENSGT00390000016025.
HOGENOMiHOG000267658.
HOVERGENiHBG054073.
InParanoidiQ9HAS3.
KOiK11536.
OMAiGCCTLLN.
OrthoDBiEOG091G05D5.
PhylomeDBiQ9HAS3.
TreeFamiTF314131.

Enzyme and pathway databases

BioCyciZFISH:G66-31706-MONOMER.
ReactomeiR-HSA-83936. Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.

Miscellaneous databases

ChiTaRSiSLC28A3. human.
GenomeRNAii64078.
PROiQ9HAS3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197506.
CleanExiHS_SLC28A3.
GenevisibleiQ9HAS3. HS.

Family and domain databases

InterProiIPR008276. C_nuclsd_transpt.
IPR018270. C_nuclsd_transpt_met_bac.
IPR030211. CNT3.
IPR011657. CNT_C_dom.
IPR002668. CNT_N_dom.
IPR011642. Gate_dom.
[Graphical view]
PANTHERiPTHR10590. PTHR10590. 1 hit.
PTHR10590:SF18. PTHR10590:SF18. 1 hit.
PfamiPF07670. Gate. 1 hit.
PF07662. Nucleos_tra2_C. 1 hit.
PF01773. Nucleos_tra2_N. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00804. nupC. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiS28A3_HUMAN
AccessioniPrimary (citable) accession number: Q9HAS3
Secondary accession number(s): A8K9Y4
, B1AML0, B2RA51, B4E2S8, F5GYE3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 130 of the entry and version 1 of the sequence. [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. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.