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    SLC28A3 solute carrier family 28 member 3 [ Homo sapiens (human) ]

    Gene ID: 64078, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SLC28A3provided by HGNC
    Official Full Name
    solute carrier family 28 member 3provided by HGNC
    Primary source
    HGNC:HGNC:16484
    See related
    Ensembl:ENSG00000197506 MIM:608269; AllianceGenome:HGNC:16484
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CNT3
    Summary
    Nucleoside transporters, such as SLC28A3, regulate multiple cellular processes, including neurotransmission, vascular tone, adenosine concentration in the vicinity of cell surface receptors, and transport and metabolism of nucleoside drugs. SLC28A3 shows broad specificity for pyrimidine and purine nucleosides (Ritzel et al., 2001 [PubMed 11032837]).[supplied by OMIM, Mar 2008]
    Expression
    Biased expression in gall bladder (RPKM 4.2), bone marrow (RPKM 3.2) and 11 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SLC28A3 in Genome Data Viewer
    Location:
    9q21.32-q21.33
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (84275457..84368727, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (96425798..96519059, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (86890372..86983642, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:86595393-86595900 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:86595901-86596409 Neighboring gene heterogeneous nuclear ribonucleoprotein K Neighboring gene uncharacterized LOC101927575 Neighboring gene RecQ mediated genome instability 1 Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 33 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:86766071-86767007 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:86787894-86788403 Neighboring gene Sharpr-MPRA regulatory region 11289 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19983 Neighboring gene NANOG hESC enhancer GRCh37_chr9:86891619-86892170 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:86892303-86893502 Neighboring gene SLC28A3 regulatory antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28502 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28504 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr9:86916903-86918102 Neighboring gene SLC28A3 intron nontranscribed chromatin-defined enhancer Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:86991346-86991846 Neighboring gene uncharacterized LOC102724036 Neighboring gene uncharacterized LOC124902192 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19984 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr9:87127109-87128308 Neighboring gene NANOG hESC enhancer GRCh37_chr9:87185076-87185832 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_108369 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28505 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19985 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28507 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28508 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:87323096-87324014 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28510 Neighboring gene neurotrophic receptor tyrosine kinase 2 Neighboring gene uncharacterized LOC124902193

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Allosteric and transport modulation of human concentrative nucleoside transporter 3 at the atomic scale. Duan H, et al. Phys Chem Chem Phys, 2021 Nov 17. PMID 34751688
    2. Substituted cysteine accessibility method analysis of human concentrative nucleoside transporter hCNT3 reveals a novel discontinuous region of functional importance within the CNT family motif (G/A)XKX3NEFVA(Y/M/F). Slugoski MD, et al. J Biol Chem, 2009 Jun 19. PMID 19380585, Free PMC Article
    3. Conserved glutamate residues Glu-343 and Glu-519 provide mechanistic insights into cation/nucleoside cotransport by human concentrative nucleoside transporter hCNT3. Slugoski MD, et al. J Biol Chem, 2009 Jun 19. PMID 19380587, Free PMC Article
    4. A splice variant of the SLC28A3 gene encodes a novel human concentrative nucleoside transporter-3 (hCNT3) protein localized in the endoplasmic reticulum. Errasti-Murugarren E, et al. FASEB J, 2009 Jan. PMID 18827020
    5. A conformationally mobile cysteine residue (Cys-561) modulates Na+ and H+ activation of human CNT3. Slugoski MD, et al. J Biol Chem, 2008 Sep 5. PMID 18621735, Free PMC Article

    See all (56) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Role of RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 Single-nucleotide Polymorphisms in the Doxorubicin-induced Cardiotoxicity in Solid Childhood Tumors.
      Title: The Role of RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 Single-nucleotide Polymorphisms in the Doxorubicin-induced Cardiotoxicity in Solid Childhood Tumors.
    2. Gene-Gene Interactions of Gemcitabine Metabolizing-Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine-Induced Hematological Toxicity.
      Title: Gene-Gene Interactions of Gemcitabine Metabolizing-Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine-Induced Hematological Toxicity.
    3. Allosteric and transport modulation of human concentrative nucleoside transporter 3 at the atomic scale.
      Title: Allosteric and transport modulation of human concentrative nucleoside transporter 3 at the atomic scale.
    4. Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters.
      Title: Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters.
    5. Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients.
      Title: Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients.
    6. Cryo-EM structure of the human concentrative nucleoside transporter CNT3.
      Title: Cryo-EM structure of the human concentrative nucleoside transporter CNT3.
    7. human CNT3 homology models generated validate previously published PCMBS SCAM data, and confirm an elevator-type mechanism of membrane transport
      Title: Inward- and outward-facing homology modeling of human concentrative nucleoside transporter 3 (hCNT3) predicts an elevator-type transport mechanism.
    8. De novo structure prediction of three N-terminal transmembrane helices of the human concentrative nucleoside transporter 3 (hCNT3) homotrimer belonging to the solute carrier 28 family of transporters (SLC28) using Rosetta program and its Broker protocol.
      Title: Rosetta Broker for membrane protein structure prediction: concentrative nucleoside transporter 3 and corticotropin-releasing factor receptor 1 test cases.
    9. CYR61 negatively regulates the nucleoside transporters hENT1 and hCNT3 in pancreatic ductal adenocarcinoma.
      Title: TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3.
    10. Data suggest that CNT3 forms a homotrimer in solution and membrane-bound inside cells; the quaternary structure creates an aqueous basin that significantly shortens the substrate translocation distance.
      Title: Human Concentrative Nucleoside Transporter 3 (hCNT3, SLC28A3) Forms a Cyclic Homotrimer.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women's Health Initiative SHARe Study.
    EBI GWAS Catalog
    Genome-wide association of lipid-lowering response to statins in combined study populations.
    EBI GWAS Catalog
    Genome-wide association study (GWAS) for molar-incisor hypomineralization (MIH).
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables nucleoside:sodium symporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables purine nucleobase transmembrane transporter activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables purine-specific nucleoside:sodium symporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables pyrimidine- and adenosine-specific:sodium symporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables uridine transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in nucleoside transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in purine nucleobase transmembrane transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in purine nucleoside transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in pyrimidine nucleobase transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pyrimidine nucleoside transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in pyrimidine-containing compound transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sodium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in uridine transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in xenobiotic metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in xenobiotic transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in brush border membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    solute carrier family 28 member 3
    Names
    concentrative Na(+)-nucleoside cotransporter 3
    concentrative Na+-nucleoside cotransporter
    solute carrier family 28 (concentrative nucleoside transporter), member 3
    solute carrier family 28 (sodium-coupled nucleoside transporter), member 3

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001199633.2 → NP_001186562.1  solute carrier family 28 member 3

      See identical proteins and their annotated locations for NP_001186562.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 both encode the same protein.
      Source sequence(s)
      AA643687, AF305210, AK022042, AK314039, AL356134
      Consensus CDS
      CCDS6670.1
      UniProtKB/Swiss-Prot
      A8K9Y4, B1AML0, B2RA51, B4E2S8, F5GYE3, Q9HAS3
      Related
      ENSP00000365413.4, ENST00000376238.5
      Conserved Domains (4) summary
      TIGR00804
      Location:201 → 612
      nupC; nucleoside transporter
      pfam01773
      Location:206 → 275
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07662
      Location:388 → 612
      Nucleos_tra2_C; Na+ dependent nucleoside transporter C-terminus
      pfam07670
      Location:287 → 383
      Gate; Nucleoside recognition

    2. NM_022127.3 → NP_071410.1  solute carrier family 28 member 3

      See identical proteins and their annotated locations for NP_071410.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same protein.
      Source sequence(s)
      AA643687, AF305210, AK022042, AL353787, AL356134
      Consensus CDS
      CCDS6670.1
      UniProtKB/Swiss-Prot
      A8K9Y4, B1AML0, B2RA51, B4E2S8, F5GYE3, Q9HAS3
      Conserved Domains (4) summary
      TIGR00804
      Location:201 → 612
      nupC; nucleoside transporter
      pfam01773
      Location:206 → 275
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07662
      Location:388 → 612
      Nucleos_tra2_C; Na+ dependent nucleoside transporter C-terminus
      pfam07670
      Location:287 → 383
      Gate; Nucleoside recognition

    RNA

    1. NR_037638.3 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) includes an alternate exon in the coding region compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA643687, AF305210, AK022042, AK304406, AL353787, AL356134

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      84275457..84368727 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011518907.3 → XP_011517209.1  solute carrier family 28 member 3 isoform X2

      Conserved Domains (4) summary
      TIGR00804
      Location:118 → 529
      nupC; nucleoside transporter
      pfam01773
      Location:123 → 192
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07662
      Location:305 → 529
      Nucleos_tra2_C; Na+ dependent nucleoside transporter C-terminus
      pfam07670
      Location:204 → 300
      Gate; Nucleoside recognition

    2. XM_011518906.3 → XP_011517208.1  solute carrier family 28 member 3 isoform X1

      See identical proteins and their annotated locations for XP_011517208.1

      Conserved Domains (4) summary
      TIGR00804
      Location:229 → 640
      nupC; nucleoside transporter
      pfam01773
      Location:234 → 303
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07662
      Location:416 → 640
      Nucleos_tra2_C; Na+ dependent nucleoside transporter C-terminus
      pfam07670
      Location:315 → 411
      Gate; Nucleoside recognition

    3. XM_011518905.3 → XP_011517207.1  solute carrier family 28 member 3 isoform X1

      See identical proteins and their annotated locations for XP_011517207.1

      Conserved Domains (4) summary
      TIGR00804
      Location:229 → 640
      nupC; nucleoside transporter
      pfam01773
      Location:234 → 303
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07662
      Location:416 → 640
      Nucleos_tra2_C; Na+ dependent nucleoside transporter C-terminus
      pfam07670
      Location:315 → 411
      Gate; Nucleoside recognition

    4. XM_011518908.3 → XP_011517210.1  solute carrier family 28 member 3 isoform X4

      Conserved Domains (4) summary
      TIGR00804
      Location:11 → 399
      nupC; nucleoside transporter
      pfam01773
      Location:13 → 62
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07662
      Location:175 → 399
      Nucleos_tra2_C; Na+ dependent nucleoside transporter C-terminus
      pfam07670
      Location:74 → 170
      Gate; Nucleoside recognition

    5. XM_047423712.1 → XP_047279668.1  solute carrier family 28 member 3 isoform X3

    6. XM_011518910.3 → XP_011517212.1  solute carrier family 28 member 3 isoform X5

      See identical proteins and their annotated locations for XP_011517212.1

      Conserved Domains (2) summary
      pfam01773
      Location:234 → 303
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07670
      Location:315 → 370
      Gate; Nucleoside recognition

    7. XM_011518909.3 → XP_011517211.1  solute carrier family 28 member 3 isoform X5

      See identical proteins and their annotated locations for XP_011517211.1

      Conserved Domains (2) summary
      pfam01773
      Location:234 → 303
      Nucleos_tra2_N; Na+ dependent nucleoside transporter N-terminus
      pfam07670
      Location:315 → 370
      Gate; Nucleoside recognition

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      96425798..96519059 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054363509.1 → XP_054219484.1  solute carrier family 28 member 3 isoform X2

    2. XM_054363508.1 → XP_054219483.1  solute carrier family 28 member 3 isoform X1

    3. XM_054363507.1 → XP_054219482.1  solute carrier family 28 member 3 isoform X1

    4. XM_054363511.1 → XP_054219486.1  solute carrier family 28 member 3 isoform X4

    5. XM_054363510.1 → XP_054219485.1  solute carrier family 28 member 3 isoform X3

    6. XM_054363513.1 → XP_054219488.1  solute carrier family 28 member 3 isoform X5

    7. XM_054363512.1 → XP_054219487.1  solute carrier family 28 member 3 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HAS3.1 GenPept UniProtKB/Swiss-Prot:Q9HAS3

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