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SLC8A3 solute carrier family 8 member A3 [ Homo sapiens (human) ]

Gene ID: 6547, updated on 27-Nov-2024

Summary

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Official Symbol
SLC8A3provided by HGNC
Official Full Name
solute carrier family 8 member A3provided by HGNC
Primary source
HGNC:HGNC:11070
See related
Ensembl:ENSG00000100678 MIM:607991; AllianceGenome:HGNC:11070
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NCX3
Summary
This gene encodes a member of the sodium/calcium exchanger integral membrane protein family. Na+/Ca2+ exchange proteins are involved in maintaining Ca2+ homeostasis in a wide variety of cell types. The protein is regulated by intracellular calcium ions and is found in both the plasma membrane and intracellular organellar membranes, where exchange of Na+ for Ca2+ occurs in an electrogenic manner. Alternative splicing has been observed for this gene and multiple variants have been described. [provided by RefSeq, Aug 2013]
Expression
Biased expression in brain (RPKM 2.0), adrenal (RPKM 0.3) and 4 other tissues See more
Orthologs
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Genomic context

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See SLC8A3 in Genome Data Viewer
Location:
14q24.2
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (70044215..70189405, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (64251720..64396975, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (70510932..70655668, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene ribosomal protein L7a pseudogene 6 Neighboring gene SPARC related modular calcium binding 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:70419797-70420298 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:70445787-70446286 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr14:70454077-70454578 Neighboring gene small nucleolar RNA, C/D box 169 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8650 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr14:70477330-70478529 Neighboring gene Sharpr-MPRA regulatory region 14883 Neighboring gene Sharpr-MPRA regulatory region 1041 Neighboring gene MPRA-validated peak2186 silencer Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:70527273-70528472 Neighboring gene Sharpr-MPRA regulatory region 1623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5884 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5885 Neighboring gene ADAM metallopeptidase domain 20 pseudogene Neighboring gene uncharacterized LOC107984686 Neighboring gene MPRA-validated peak2187 silencer Neighboring gene histone deacetylase complex subunit SAP25-like

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
  • 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. Na(+)-Ca2+ exchanger: physiology and pharmacology. Matsuda T, et al. Jpn J Pharmacol, 1997 May. PMID 9195292
  2. Sodium/calcium exchange: its physiological implications. Blaustein MP, et al. Physiol Rev, 1999 Jul. PMID 10390518
  3. The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms. Gabellini N, et al. Gene, 2002 Sep 18. PMID 12406570
  4. The gene promoter of human Na+/Ca2+ exchanger isoform 3 (SLC8A3) is controlled by cAMP and calcium. Gabellini N, et al. Ann N Y Acad Sci, 2002 Nov. PMID 12502570
  5. Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle. Liu T, et al. Eur J Cell Biol, 2018 Apr. PMID 29526322

See all (42) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Sodium-calcium exchanger-3 regulates pain ""wind-up"": From human psychophysics to spinal mechanisms.
    Title: Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.
  2. The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.
    Title: The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.
  3. These results...suggest that cells can use a dynamic Ca(2+) signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle
    Title: Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle.
  4. Structure-Dynamic Coupling Through Ca(2+)-Binding Regulatory Domains of Mammalian NCX Isoform/Splice Variants
    Title: Structure-Dynamic Coupling Through Ca(2+)-Binding Regulatory Domains of Mammalian NCX Isoform/Splice Variants.
  5. stimulation of NCX3 by PKA occurred through residue S524. This effect may well participate in the fight-or-flight response in skeletal muscle and the long-term potentiation in hippocampus.
    Title: Differential regulation of the Na(+)-Ca(2+) exchanger 3 (NCX3) by protein kinase PKC and PKA.
  6. In the discovery phase, 60 loci not previously associated with rheumatoid arthritis risk showed evidence for association and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level. When combining the discovery and validation cohorts, an intronic SNP in SLC8A3 was found to be associated with ACPA-positive rheumatoid arthritis at a genome-wide level of significance.
    Title: A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-positive rheumatoid arthritis.
  7. Ayloid beta mediates calpain cleavage of NCX3 in Alzheimer's disease brain.
    Title: Calpain cleavage and inactivation of the sodium calcium exchanger-3 occur downstream of Aβ in Alzheimer's disease.
  8. human macrophages and monocytes express NCX1 and NCX3 that operate in a bidirectional manner to restore [Ca(2+)](i) to generate Ca(2+) signals and to induce TNF-alpha production.
    Title: Human macrophages and monocytes express functional Na(+)/Ca (2+) exchangers 1 and 3.
  9. Functional studies, as well as mRNA and protein expression analyses, revealed that NCX1 and NCX3, but not NCX2, were divergently modulated during OPC differentiation into oligodendrocyte.
    Title: New roles of NCX in glial cells: activation of microglia in ischemia and differentiation of oligodendrocytes.
  10. the large cytosolic loop of NCX1, NCX2, and NCX3 is involved in acquisition of immunosuppressive drug specificity
    Title: Immunosuppressive drugs, immunophilins, and functional expression of NCX isoforms.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Genetic variants near PDGFRA are associated with corneal curvature in Australians.
EBI GWAS Catalog
Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
EBI GWAS Catalog
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
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)

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 calcium:sodium antiporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium:sodium antiporter activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables calcium:sodium antiporter activity TAS
Traceable Author Statement
more info
  
enables calmodulin binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium ion import across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in calcium ion transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cell communication IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to hypoxia ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in hematopoietic progenitor cell differentiation IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within intracellular calcium ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in intracellular calcium ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in learning ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within learning or memory ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within long-term synaptic potentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in long-term synaptic potentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in memory ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in mitochondrial calcium ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in mitochondrial calcium ion transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within modulation of excitatory postsynaptic potential ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in monoatomic ion transport TAS
Traceable Author Statement
more info
  
involved_in myelination ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within negative regulation of protein serine/threonine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in oligodendrocyte differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of cardiac conduction TAS
Traceable Author Statement
more info
  
involved_in regulation of skeletal muscle contraction ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in sodium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in sodium ion transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within synapse organization ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in anchoring junction IEA
Inferred from Electronic Annotation
more info
  
is_active_in axon IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in axon ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in axon terminus ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in dendrite ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in dendritic spine IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in mitochondrial outer membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in neuromuscular junction ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in neuronal cell body ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
located_in perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
is_active_in postsynapse IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in postsynaptic density ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in sarcolemma IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in sarcolemma ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in sarcoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in synapse IDA
Inferred from Direct Assay
more info
 PubMed 
located_in synapse ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
sodium/calcium exchanger 3
Names
Na(+)/Ca(2+)-exchange protein 3
sodium/calcium exchanger SLC8A3
solute carrier family 8 (sodium/calcium exchanger), 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.

Genomic

  1. NG_047080.1 RefSeqGene

    Range
    39662..184398
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001130417.3 → NP_001123889.1  sodium/calcium exchanger 3 isoform G

    See identical proteins and their annotated locations for NP_001123889.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (g, also known as NCX3-tN.2) differs in the presence and absence of exons at its 5' end, compared to variant c. These differences result in a distinct 5' UTR and translation initiation at a downstream start codon, and an isoform (G) that is shorter than isoform C.
    Source sequence(s)
    AF510501, AL135747, BC142969, BX098112, DA351808
    Consensus CDS
    CCDS45131.1
    UniProtKB/TrEMBL
    B3KV80
    Related
    ENSP00000216568.7, ENST00000216568.11
    Conserved Domains (1) summary
    cl02522
    Location:10 → 298
    Calx-beta; Calx-beta domain

  2. NM_033262.5 → NP_150287.1  sodium/calcium exchanger 3 isoform A precursor

    See identical proteins and their annotated locations for NP_150287.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) includes an alternate in-frame exon, lacks another alternate in-frame exon and uses an alternate in-frame splice site in the mid coding region, compared to variant c. The encoded isoform (A) is shorter than isoform C.
    Source sequence(s)
    AF510501, AJ304852, AL135747, BX098112
    Consensus CDS
    CCDS9799.1
    UniProtKB/TrEMBL
    A7E240
    Related
    ENSP00000433531.1, ENST00000528359.6
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 925
    caca; sodium/calcium exchanger 1

  3. NM_058240.4 → NP_489479.1  sodium/calcium exchanger 3 isoform B precursor

    See identical proteins and their annotated locations for NP_489479.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) uses an alternate in-frame splice site in the mid coding region, compared to variant c. The encoded isoform (B) is shorter than isoform C.
    Source sequence(s)
    AF510502, AJ304853, AL135747, BX098112
    Consensus CDS
    CCDS53904.1
    UniProtKB/TrEMBL
    A7E240
    Related
    ENSP00000436688.1, ENST00000534137.5
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 924
    caca; sodium/calcium exchanger 1

  4. NM_182932.3 → NP_891977.1  sodium/calcium exchanger 3 isoform D precursor

    See identical proteins and their annotated locations for NP_891977.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (d, also known as NCX3.2), lacks an alternate in-frame exon in the mid coding region, compared to variant c. The encoded isoform (D) is shorter than isoform C.
    Source sequence(s)
    AF510501, AL135747, BX098112
    Consensus CDS
    CCDS9800.1
    UniProtKB/TrEMBL
    A7E240
    Related
    ENSP00000349392.3, ENST00000356921.7
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 921
    caca; sodium/calcium exchanger 1

  5. NM_182936.3 → NP_891981.1  sodium/calcium exchanger 3 isoform F

    See identical proteins and their annotated locations for NP_891981.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (f, also known as NCX3-tN.1) differs in the presence and absence of exons at its 5' end, compared to variant c. These differences result in a distinct 5' UTR and translation initiation at a downstream start codon, and an isoform (F) that is shorter than isoform C.
    Source sequence(s)
    AF510501, AK096553, AL135747, BX098112, DA351808
    Consensus CDS
    CCDS41967.1
    UniProtKB/TrEMBL
    B3KU59
    Related
    ENSP00000377863.2, ENST00000394330.6
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 284
    caca; sodium/calcium exchanger 1

  6. NM_183002.3 → NP_892114.1  sodium/calcium exchanger 3 isoform C precursor

    See identical proteins and their annotated locations for NP_892114.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (c, also known as NCX3.3), encodes the longest isoform (C).
    Source sequence(s)
    AF510502, AL135747, BX098112
    Consensus CDS
    CCDS35498.1
    UniProtKB/Swiss-Prot
    P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2
    UniProtKB/TrEMBL
    A7E240
    Related
    ENSP00000370669.2, ENST00000381269.6
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 927
    caca; sodium/calcium exchanger 1

RNA

  1. NR_104122.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (h) lacks two alternate internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant c, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF510503, AL135747, BX098112
    Related
    ENST00000494208.5

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_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    70044215..70189405 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047431711.1 → XP_047287667.1  sodium/calcium exchanger 3 isoform X4

  2. XM_017021608.2 → XP_016877097.1  sodium/calcium exchanger 3 isoform X3

    UniProtKB/TrEMBL
    A7E240
    Related
    ENSP00000516120.1, ENST00000705391.1
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 921
    caca; sodium/calcium exchanger 1

  3. XM_017021606.2 → XP_016877095.1  sodium/calcium exchanger 3 isoform X1

    UniProtKB/Swiss-Prot
    P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2
    UniProtKB/TrEMBL
    A7E240
    Conserved Domains (1) summary
    TIGR00845
    Location:1 → 927
    caca; sodium/calcium exchanger 1

  4. XM_017021609.2 → XP_016877098.1  sodium/calcium exchanger 3 isoform X4

    UniProtKB/TrEMBL
    A7E240
    Conserved Domains (4) summary
    TIGR00845
    Location:1 → 920
    caca; sodium/calcium exchanger 1
    pfam01699
    Location:746 → 911
    Na_Ca_ex; Sodium/calcium exchanger protein
    pfam03160
    Location:395 → 485
    Calx-beta; Calx-beta domain
    pfam16494
    Location:253 → 374
    Na_Ca_ex_C; C-terminal extension of sodium/calcium exchanger domain

  5. XM_017021607.2 → XP_016877096.1  sodium/calcium exchanger 3 isoform X2

    UniProtKB/TrEMBL
    A7E240
    Conserved Domains (4) summary
    TIGR00845
    Location:1 → 926
    caca; sodium/calcium exchanger 1
    pfam01699
    Location:752 → 917
    Na_Ca_ex; Sodium/calcium exchanger protein
    pfam03160
    Location:395 → 485
    Calx-beta; Calx-beta domain
    pfam16494
    Location:253 → 374
    Na_Ca_ex_C; C-terminal extension of sodium/calcium exchanger domain

  6. XM_006720240.4 → XP_006720303.1  sodium/calcium exchanger 3 isoform X7

    See identical proteins and their annotated locations for XP_006720303.1

    UniProtKB/TrEMBL
    B3KV80
    Conserved Domains (1) summary
    pfam01699
    Location:130 → 295
    Na_Ca_ex; Sodium/calcium exchanger protein

  7. XM_017021611.2 → XP_016877100.1  sodium/calcium exchanger 3 isoform X6

    UniProtKB/TrEMBL
    B3KV80
    Conserved Domains (1) summary
    TIGR00845
    Location:4 → 311
    caca; sodium/calcium exchanger 1

  8. XM_017021610.2 → XP_016877099.1  sodium/calcium exchanger 3 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    64251720..64396975 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054376628.1 → XP_054232603.1  sodium/calcium exchanger 3 isoform X3

  2. XM_054376629.1 → XP_054232604.1  sodium/calcium exchanger 3 isoform X4

  3. XM_054376627.1 → XP_054232602.1  sodium/calcium exchanger 3 isoform X2

  4. XM_054376626.1 → XP_054232601.1  sodium/calcium exchanger 3 isoform X1

    UniProtKB/Swiss-Prot
    P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2

  5. XM_054376630.1 → XP_054232605.1  sodium/calcium exchanger 3 isoform X4

  6. XM_054376632.1 → XP_054232607.1  sodium/calcium exchanger 3 isoform X7

  7. XM_054376631.1 → XP_054232606.1  sodium/calcium exchanger 3 isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_182933.1: Suppressed sequence

    Description
    NM_182933.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P57103.2 GenPept UniProtKB/Swiss-Prot:P57103

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