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Protein

Equilibrative nucleoside transporter 3

Gene

SLC29A3

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

Functioni

Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). Mediates transport of adenine, adenosine and uridine, as well as several nucleoside analog drugs, such as anticancer and antiviral agents, including cladribine, cordycepin, tubercidin and AZT. Does not transport hypoxanthine.1 Publication

Kineticsi

  1. KM=1.86 mM for adenosine1 Publication
  2. KM=2.02 mM for uridine1 Publication

    pH dependencei

    Optimum pH is 5.5 for adenosine uptake.1 Publication

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Biological processi

    Transport

    Enzyme and pathway databases

    BioCyciZFISH:G66-33817-MONOMER.
    ReactomeiR-HSA-83936. Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.

    Protein family/group databases

    TCDBi2.A.57.1.6. the equilibrative nucleoside transporter (ent) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Equilibrative nucleoside transporter 3
    Short name:
    hENT3
    Alternative name(s):
    Solute carrier family 29 member 3
    Gene namesi
    Name:SLC29A3
    Synonyms:ENT3
    ORF Names:UNQ717/PRO1380
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:23096. SLC29A3.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 53CytoplasmicSequence analysisAdd BLAST53
    Transmembranei54 – 74HelicalSequence analysisAdd BLAST21
    Topological domaini75 – 105ExtracellularSequence analysisAdd BLAST31
    Transmembranei106 – 126HelicalSequence analysisAdd BLAST21
    Topological domaini127 – 134CytoplasmicSequence analysis8
    Transmembranei135 – 155HelicalSequence analysisAdd BLAST21
    Topological domaini156 – 162ExtracellularSequence analysis7
    Transmembranei163 – 183HelicalSequence analysisAdd BLAST21
    Topological domaini184 – 199CytoplasmicSequence analysisAdd BLAST16
    Transmembranei200 – 220HelicalSequence analysisAdd BLAST21
    Topological domaini221 – 230ExtracellularSequence analysis10
    Transmembranei231 – 251HelicalSequence analysisAdd BLAST21
    Topological domaini252 – 305CytoplasmicSequence analysisAdd BLAST54
    Transmembranei306 – 326HelicalSequence analysisAdd BLAST21
    Topological domaini327 – 337ExtracellularSequence analysisAdd BLAST11
    Transmembranei338 – 358HelicalSequence analysisAdd BLAST21
    Topological domaini359 – 377CytoplasmicSequence analysisAdd BLAST19
    Transmembranei378 – 398HelicalSequence analysisAdd BLAST21
    Topological domaini399 – 415ExtracellularSequence analysisAdd BLAST17
    Transmembranei416 – 436HelicalSequence analysisAdd BLAST21
    Topological domaini437 – 454CytoplasmicSequence analysisAdd BLAST18
    Transmembranei455 – 475HelicalSequence analysisAdd BLAST21

    GO - Cellular componenti

    • integral component of membrane Source: UniProtKB-KW
    • late endosome membrane Source: UniProtKB-SubCell
    • lysosomal membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Endosome, Lysosome, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Histiocytosis-lymphadenopathy plus syndrome (HLAS)8 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA syndrome characterized by the combination of features from 2 or more of four histiocytic disorders, originally thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC features include joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes. SHML causes lymph node enlargement in children frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. H syndrome is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss is found in about half of patients. PHID is characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome.
    See also OMIM:602782
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_067801116M → R in HLAS; partially retained in the endoplasmic reticulum; results in reduced nucleoside transport. 2 PublicationsCorresponds to variant rs267607057dbSNPEnsembl.1
    Natural variantiVAR_067802134R → C in HLAS. 1 Publication1
    Natural variantiVAR_067804184S → R in HLAS. 1 Publication1
    Natural variantiVAR_067806363R → Q in HLAS. 2 PublicationsCorresponds to variant rs387907066dbSNPEnsembl.1
    Natural variantiVAR_067807363R → W in HLAS. 1 PublicationCorresponds to variant rs387907067dbSNPEnsembl.1
    Natural variantiVAR_057884427G → S in HLAS; almost total loss of nucleoside transport. 3 PublicationsCorresponds to variant rs121912583dbSNPEnsembl.1
    Natural variantiVAR_057885437G → R in HLAS; results in reduced nucleoside transport. 7 PublicationsCorresponds to variant rs121912584dbSNPEnsembl.1
    Natural variantiVAR_067809449T → R in HLAS; results in reduced nucleoside transport. 2 PublicationsCorresponds to variant rs267607058dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi31L → A: Localization at the cell surface; when associated with A-32. 1 Publication1
    Mutagenesisi32L → A: Localization at the cell surface; when associated with A-31. 1 Publication1
    Mutagenesisi427G → A, F, Y or T: Results in impaired nucleoside transport. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi55315.
    MalaCardsiSLC29A3.
    MIMi602782. phenotype.
    OpenTargetsiENSG00000198246.
    Orphaneti1782. Dysosteosclerosis.
    168569. H syndrome.
    PharmGKBiPA134950750.

    Polymorphism and mutation databases

    BioMutaiSLC29A3.
    DMDMi313104188.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002093431 – 475Equilibrative nucleoside transporter 3Add BLAST475

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei21PhosphoserineBy similarity1
    Modified residuei23PhosphoserineCombined sources1
    Glycosylationi84N-linked (GlcNAc...)Sequence analysis1

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    EPDiQ9BZD2.
    MaxQBiQ9BZD2.
    PaxDbiQ9BZD2.
    PeptideAtlasiQ9BZD2.
    PRIDEiQ9BZD2.

    PTM databases

    iPTMnetiQ9BZD2.
    PhosphoSitePlusiQ9BZD2.

    Expressioni

    Tissue specificityi

    Widely expressed in both adult and fetal tissues. Highest levels in placenta, uterus, ovary, spleen, lymph node and bone marrow. Lowest levels in brain and heart.1 Publication

    Gene expression databases

    BgeeiENSG00000198246.
    CleanExiHS_SLC29A3.
    GenevisibleiQ9BZD2. HS.

    Organism-specific databases

    HPAiHPA054976.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000362285.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BZD2.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1479. Eukaryota.
    ENOG410Y3MT. LUCA.
    GeneTreeiENSGT00390000002232.
    HOVERGENiHBG108444.
    InParanoidiQ9BZD2.
    KOiK15014.
    OMAiYYMRPVL.
    OrthoDBiEOG091G09WB.
    PhylomeDBiQ9BZD2.
    TreeFamiTF313950.

    Family and domain databases

    InterProiIPR030193. ENT3.
    IPR002259. Eqnu_transpt.
    [Graphical view]
    PANTHERiPTHR10332. PTHR10332. 1 hit.
    PTHR10332:SF17. PTHR10332:SF17. 1 hit.
    PfamiPF01733. Nucleoside_tran. 1 hit.
    [Graphical view]
    PIRSFiPIRSF016379. ENT. 1 hit.
    PRINTSiPR01130. DERENTRNSPRT.

    Sequences (2)i

    Sequence statusi: Complete.

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

    Isoform 1 (identifier: Q9BZD2-1) [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
    MAVVSEDDFQ HSSNSTYRTT SSSLRADQEA LLEKLLDRPP PGLQRPEDRF
    60 70 80 90 100
    CGTYIIFFSL GIGSLLPWNF FITAKEYWMF KLRNSSSPAT GEDPEGSDIL
    110 120 130 140 150
    NYFESYLAVA STVPSMLCLV ANFLLVNRVA VHIRVLASLT VILAIFMVIT
    160 170 180 190 200
    ALVKVDTSSW TRGFFAVTIV CMVILSGAST VFSSSIYGMT GSFPMRNSQA
    210 220 230 240 250
    LISGGAMGGT VSAVASLVDL AASSDVRNSA LAFFLTATVF LVLCMGLYLL
    260 270 280 290 300
    LSRLEYARYY MRPVLAAHVF SGEEELPQDS LSAPSVASRF IDSHTPPLRP
    310 320 330 340 350
    ILKKTASLGF CVTYVFFITS LIYPAICTNI ESLNKGSGSL WTTKFFIPLT
    360 370 380 390 400
    TFLLYNFADL CGRQLTAWIQ VPGPNSKALP GFVLLRTCLI PLFVLCNYQP
    410 420 430 440 450
    RVHLKTVVFQ SDVYPALLSS LLGLSNGYLS TLALLYGPKI VPRELAEATG
    460 470
    VVMSFYVCLG LTLGSACSTL LVHLI
    Length:475
    Mass (Da):51,815
    Last modified:November 30, 2010 - v3
    Checksum:iDBF0918ECA6D5A70
    GO
    Isoform 2 (identifier: Q9BZD2-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-146: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:329
    Mass (Da):35,502
    Checksum:iA06B3DCAB26EB536
    GO

    Sequence cautioni

    The sequence BAA92041 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti32L → P in BAG37097 (PubMed:14702039).Curated1
    Sequence conflicti112T → A in BAA92041 (PubMed:14702039).Curated1
    Sequence conflicti306A → S in BAG65311 (PubMed:14702039).Curated1
    Sequence conflicti370Q → R in BAA92041 (PubMed:14702039).Curated1
    Sequence conflicti453M → I in BAG65311 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_01866218R → G.1 PublicationCorresponds to variant rs2277257dbSNPEnsembl.1
    Natural variantiVAR_067801116M → R in HLAS; partially retained in the endoplasmic reticulum; results in reduced nucleoside transport. 2 PublicationsCorresponds to variant rs267607057dbSNPEnsembl.1
    Natural variantiVAR_067802134R → C in HLAS. 1 Publication1
    Natural variantiVAR_018663158S → F.4 PublicationsCorresponds to variant rs780668dbSNPEnsembl.1
    Natural variantiVAR_067803163G → V.1 PublicationCorresponds to variant rs143557881dbSNPEnsembl.1
    Natural variantiVAR_067804184S → R in HLAS. 1 Publication1
    Natural variantiVAR_018664239V → I.5 PublicationsCorresponds to variant rs2252996dbSNPEnsembl.1
    Natural variantiVAR_067805281L → P.1 PublicationCorresponds to variant rs79737301dbSNPEnsembl.1
    Natural variantiVAR_018665326I → V.5 PublicationsCorresponds to variant rs2487068dbSNPEnsembl.1
    Natural variantiVAR_067806363R → Q in HLAS. 2 PublicationsCorresponds to variant rs387907066dbSNPEnsembl.1
    Natural variantiVAR_067807363R → W in HLAS. 1 PublicationCorresponds to variant rs387907067dbSNPEnsembl.1
    Natural variantiVAR_067808407V → M.1 PublicationCorresponds to variant rs144517514dbSNPEnsembl.1
    Natural variantiVAR_057884427G → S in HLAS; almost total loss of nucleoside transport. 3 PublicationsCorresponds to variant rs121912583dbSNPEnsembl.1
    Natural variantiVAR_057885437G → R in HLAS; results in reduced nucleoside transport. 7 PublicationsCorresponds to variant rs121912584dbSNPEnsembl.1
    Natural variantiVAR_067809449T → R in HLAS; results in reduced nucleoside transport. 2 PublicationsCorresponds to variant rs267607058dbSNPEnsembl.1
    Natural variantiVAR_018666452V → E.Corresponds to variant rs999940dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0374361 – 146Missing in isoform 2. 1 PublicationAdd BLAST146

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF326987 mRNA. Translation: AAK00958.1.
    BK000392 Genomic DNA. Translation: DAA00364.1.
    AY288928 mRNA. Translation: AAP41133.1.
    AY358686 mRNA. Translation: AAQ89049.1.
    AK002022 mRNA. Translation: BAA92041.1. Different initiation.
    AK314497 mRNA. Translation: BAG37097.1.
    AK304503 mRNA. Translation: BAG65311.1.
    AK316152 mRNA. Translation: BAH14523.1.
    AL359183, AL359384 Genomic DNA. Translation: CAI13424.1.
    AL359384, AL359183 Genomic DNA. Translation: CAI16088.1.
    BC000223 mRNA. Translation: AAH00223.1.
    BC041575 mRNA. Translation: AAH41575.1.
    BC120996 mRNA. Translation: AAI20997.1.
    BC120997 mRNA. Translation: AAI20998.1.
    CCDSiCCDS7310.1. [Q9BZD2-1]
    RefSeqiNP_001167569.1. NM_001174098.1.
    NP_060814.4. NM_018344.5. [Q9BZD2-1]
    XP_016871866.1. XM_017016377.1. [Q9BZD2-2]
    UniGeneiHs.438419.

    Genome annotation databases

    EnsembliENST00000373189; ENSP00000362285; ENSG00000198246. [Q9BZD2-1]
    GeneIDi55315.
    KEGGihsa:55315.
    UCSCiuc001jrr.5. human. [Q9BZD2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF326987 mRNA. Translation: AAK00958.1.
    BK000392 Genomic DNA. Translation: DAA00364.1.
    AY288928 mRNA. Translation: AAP41133.1.
    AY358686 mRNA. Translation: AAQ89049.1.
    AK002022 mRNA. Translation: BAA92041.1. Different initiation.
    AK314497 mRNA. Translation: BAG37097.1.
    AK304503 mRNA. Translation: BAG65311.1.
    AK316152 mRNA. Translation: BAH14523.1.
    AL359183, AL359384 Genomic DNA. Translation: CAI13424.1.
    AL359384, AL359183 Genomic DNA. Translation: CAI16088.1.
    BC000223 mRNA. Translation: AAH00223.1.
    BC041575 mRNA. Translation: AAH41575.1.
    BC120996 mRNA. Translation: AAI20997.1.
    BC120997 mRNA. Translation: AAI20998.1.
    CCDSiCCDS7310.1. [Q9BZD2-1]
    RefSeqiNP_001167569.1. NM_001174098.1.
    NP_060814.4. NM_018344.5. [Q9BZD2-1]
    XP_016871866.1. XM_017016377.1. [Q9BZD2-2]
    UniGeneiHs.438419.

    3D structure databases

    ProteinModelPortaliQ9BZD2.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000362285.

    Protein family/group databases

    TCDBi2.A.57.1.6. the equilibrative nucleoside transporter (ent) family.

    PTM databases

    iPTMnetiQ9BZD2.
    PhosphoSitePlusiQ9BZD2.

    Polymorphism and mutation databases

    BioMutaiSLC29A3.
    DMDMi313104188.

    Proteomic databases

    EPDiQ9BZD2.
    MaxQBiQ9BZD2.
    PaxDbiQ9BZD2.
    PeptideAtlasiQ9BZD2.
    PRIDEiQ9BZD2.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000373189; ENSP00000362285; ENSG00000198246. [Q9BZD2-1]
    GeneIDi55315.
    KEGGihsa:55315.
    UCSCiuc001jrr.5. human. [Q9BZD2-1]

    Organism-specific databases

    CTDi55315.
    DisGeNETi55315.
    GeneCardsiSLC29A3.
    H-InvDBHIX0008903.
    HGNCiHGNC:23096. SLC29A3.
    HPAiHPA054976.
    MalaCardsiSLC29A3.
    MIMi602782. phenotype.
    612373. gene.
    neXtProtiNX_Q9BZD2.
    OpenTargetsiENSG00000198246.
    Orphaneti1782. Dysosteosclerosis.
    168569. H syndrome.
    PharmGKBiPA134950750.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1479. Eukaryota.
    ENOG410Y3MT. LUCA.
    GeneTreeiENSGT00390000002232.
    HOVERGENiHBG108444.
    InParanoidiQ9BZD2.
    KOiK15014.
    OMAiYYMRPVL.
    OrthoDBiEOG091G09WB.
    PhylomeDBiQ9BZD2.
    TreeFamiTF313950.

    Enzyme and pathway databases

    BioCyciZFISH:G66-33817-MONOMER.
    ReactomeiR-HSA-83936. Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.

    Miscellaneous databases

    ChiTaRSiSLC29A3. human.
    GenomeRNAii55315.
    PROiQ9BZD2.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000198246.
    CleanExiHS_SLC29A3.
    GenevisibleiQ9BZD2. HS.

    Family and domain databases

    InterProiIPR030193. ENT3.
    IPR002259. Eqnu_transpt.
    [Graphical view]
    PANTHERiPTHR10332. PTHR10332. 1 hit.
    PTHR10332:SF17. PTHR10332:SF17. 1 hit.
    PfamiPF01733. Nucleoside_tran. 1 hit.
    [Graphical view]
    PIRSFiPIRSF016379. ENT. 1 hit.
    PRINTSiPR01130. DERENTRNSPRT.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiS29A3_HUMAN
    AccessioniPrimary (citable) accession number: Q9BZD2
    Secondary accession number(s): B2RB50
    , B4E2Z9, B7ZA37, Q0VAM9, Q5T465, Q7RTT8, Q8IVZ0, Q9BWI2, Q9NUS9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 24, 2004
    Last sequence update: November 30, 2010
    Last modified: November 30, 2016
    This is version 129 of the entry and version 3 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 10
      Human chromosome 10: 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.