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    ATP2B3 ATPase plasma membrane Ca2+ transporting 3 [ Homo sapiens (human) ]

    Gene ID: 492, updated on 11-Apr-2024

    Summary

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    Official Symbol
    ATP2B3provided by HGNC
    Official Full Name
    ATPase plasma membrane Ca2+ transporting 3provided by HGNC
    Primary source
    HGNC:HGNC:816
    See related
    Ensembl:ENSG00000067842 MIM:300014; AllianceGenome:HGNC:816
    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
    CLA2; OPCA; PMCA3; SCAX1; CFAP39; PMCA3a
    Summary
    The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 3. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in brain (RPKM 3.7) and adrenal (RPKM 2.1) See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    Xq28
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (153517642..153582929)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (151791198..151856492)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (152783100..152848387)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene HAUS augmin like complex subunit 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:152753877-152754691 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:152756808-152757380 Neighboring gene extracellular matrix protein X-linked, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30035 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30036 Neighboring gene biglycan Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:152809330-152810182 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:152825847-152826631 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:152831014-152831626 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21064 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21065 Neighboring gene uncharacterized LOC105373383 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21066 Neighboring gene cyclin Q

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. The ataxia-linked E1081Q mutation affects the sub-plasma membrane Ca(2+)-microdomains by tuning PMCA3 activity. Vallese F, et al. Cell Death Dis, 2022 Oct 7. PMID 36207321, Free PMC Article
    2. A novel PMCA3 mutation in an ataxic patient with hypomorphic phosphomannomutase 2 (PMM2) heterozygote mutations: Biochemical characterization of the pump defect. Vicario M, et al. Biochim Biophys Acta Mol Basis Dis, 2017 Dec. PMID 28807751
    3. Cellular Pathophysiology of an Adrenal Adenoma-Associated Mutant of the Plasma Membrane Ca(2+)-ATPase ATP2B3. Tauber P, et al. Endocrinology, 2016 Jun. PMID 27035656
    4. Mutation of plasma membrane Ca2+ ATPase isoform 3 in a family with X-linked congenital cerebellar ataxia impairs Ca2+ homeostasis. Zanni G, et al. Proc Natl Acad Sci U S A, 2012 Sep 4. PMID 22912398, Free PMC Article
    5. Placental calcium transporter (PMCA3) gene expression predicts intrauterine bone mineral accrual. Martin R, et al. Bone, 2007 May. PMID 17336174

    See all (51) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The ataxia-linked E1081Q mutation affects the sub-plasma membrane Ca(2+)-microdomains by tuning PMCA3 activity.
      Title: The ataxia-linked E1081Q mutation affects the sub-plasma membrane Ca(2+)-microdomains by tuning PMCA3 activity.
    2. Authors report a novel PMCA3 mutation (G733R substitution) in the catalytic P-domain of the pump in a patient affected by non-progressive ataxia, muscular hypotonia, dysmetria and nystagmus.
      Title: A novel PMCA3 mutation in an ataxic patient with hypomorphic phosphomannomutase 2 (PMM2) heterozygote mutations: Biochemical characterization of the pump defect.
    3. The ataxia related G1107D mutation of the PMCA 3 impairs its calcium pumping function. The mutation affects the interplay of calmodulin with its binding domain on the pump, decreasing its stimulation.
      Title: The ataxia related G1107D mutation of the plasma membrane Ca(2+) ATPase isoform 3 affects its interplay with calmodulin and the autoinhibition process.
    4. In summary, the APA-associated ATP2B3(Leu425_Val426del) mutant promotes aldosterone production by at least 2 different mechanisms: 1) a reduced Ca(2+) export due to the loss of the physiological pump function; and 2) an increased Ca(2+) influx due to opening of depolarization-activated Ca(2+) channels as well as a possible Ca(2+) leak through the mutated pump.
      Title: Cellular Pathophysiology of an Adrenal Adenoma-Associated Mutant of the Plasma Membrane Ca(2+)-ATPase ATP2B3.
    5. Mutations in ATP2B3 gene is associated with aldosterone-producing adenomas.
      Title: Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.
    6. Different mutations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D) are found in different aldosterone-producing nodules from the same adrenal, suggesting that somatic mutations are independent events triggered by mechanisms that remain to be identified.
      Title: Different Somatic Mutations in Multinodular Adrenals With Aldosterone-Producing Adenoma.
    7. Novel PMCA3 missense mutation co-occurring with a heterozygous mutation in LAMA1 impaired cellular Ca2+ homeostasis in patients with Cerebellar Ataxia.
      Title: A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.
    8. Somatic mutations found in KCNJ5, ATP1A1, and ATP2B3 appear to be the driving forces for a higher aldosterone production and proliferations of glomerulosa cells.
      Title: Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas.
    9. ATP2B3 mutations are present in aldosterone-producineg adenomas that result in an increase in CYP11B2 gene expression and may account for the dysregulated aldosterone production in a subset of patients with sporadic primary aldosteronism.
      Title: Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas.
    10. Somatic mutations in ATP2B3 gene leads to aldosterone-producing adenomas and secondary hypertension.
      Title: Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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

    Associated conditions

    Description Tests
    X-linked progressive cerebellar ataxia
    MedGen: C0796205 OMIM: 302500 GeneReviews: Not available
    		Compare labs

    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 ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables P-type calcium transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables P-type calcium transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables PDZ domain binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 export across plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in monoatomic ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of cardiac conduction TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of cytosolic calcium ion concentration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of cytosolic calcium ion concentration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of presynaptic cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in GABA-ergic synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in GABA-ergic synapse IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    is_active_in GABA-ergic synapse NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular vesicle HDA PubMed 
    is_active_in glutamatergic synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in glutamatergic synapse IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    is_active_in glutamatergic synapse NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in intracellular membrane-bounded organelle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in parallel fiber ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in parallel fiber to Purkinje cell synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in presynaptic membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    plasma membrane calcium-transporting ATPase 3
    Names
    ATPase, Ca++ transporting, plasma membrane 3
    cilia and flagella associated protein 39
    plasma membrane calcium ATPase
    plasma membrane calcium pump
    NP_001001344.1
    NP_001375289.1
    NP_001375290.1
    NP_001375291.1
    NP_001397637.1
    NP_068768.2
    XP_005274746.1
    XP_005274748.1
    XP_011529479.1
    XP_016885042.1
    XP_024308154.1
    XP_047298097.1
    XP_047298098.1
    XP_054183106.1
    XP_054183107.1
    XP_054183108.1
    XP_054183109.1
    XP_054183110.1
    XP_054183111.1

    NCBI Reference Sequences (RefSeq)

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    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_015896.2 RefSeqGene

      Range
      5002..70289
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001001344.3 → NP_001001344.1  plasma membrane calcium-transporting ATPase 3 isoform 3b

      See identical proteins and their annotated locations for NP_001001344.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region, which leads to a frameshift, compared to variant 1. The resulting isoform (3b) contains a longer and distinct C-terminus compared to isoform 3a. Variants 2 and 4 encode the same isoform.
      Source sequence(s)
      AF274858, U82695
      Consensus CDS
      CCDS35440.1
      UniProtKB/Swiss-Prot
      B7WNR8, B7WNY5, Q12995, Q16720, Q16858
      Related
      ENSP00000263519.4, ENST00000263519.5
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1146
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    2. NM_001388360.1 → NP_001375289.1  plasma membrane calcium-transporting ATPase 3 isoform 3a

      Status: REVIEWED

      Description
      Transcript Variant: Variants 1 and 3 encode the same isoform (3a).
      Source sequence(s)
      AF274858, U82695
      Consensus CDS
      CCDS14722.1
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1145
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    3. NM_001388361.1 → NP_001375290.1  plasma membrane calcium-transporting ATPase 3 isoform 3b

      Status: REVIEWED

      Description
      Transcript Variant: Variants 2 and 4 encode the same isoform (3b).
      Source sequence(s)
      AF274858, U82695
      Consensus CDS
      CCDS35440.1
      UniProtKB/Swiss-Prot
      B7WNR8, B7WNY5, Q12995, Q16720, Q16858
      Related
      ENSP00000343886.2, ENST00000349466.6
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1146
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    4. NM_001388362.1 → NP_001375291.1  plasma membrane calcium-transporting ATPase 3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AF274858, U82695
      Related
      ENST00000684004.1
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1114
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    5. NM_001410708.1 → NP_001397637.1  plasma membrane calcium-transporting ATPase 3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AF274858, U82695
      Consensus CDS
      CCDS94697.1

    6. NM_021949.4 → NP_068768.2  plasma membrane calcium-transporting ATPase 3 isoform 3a

      See identical proteins and their annotated locations for NP_068768.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript, but encodes the shortest isoform (3a). Variants 1 and 3 encode the same isoform.
      Source sequence(s)
      AF274858, U82695
      Consensus CDS
      CCDS14722.1
      UniProtKB/Swiss-Prot
      Q16720
      Related
      ENSP00000352062.3, ENST00000359149.9
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1145
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      153517642..153582929
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005274689.4 → XP_005274746.1  plasma membrane calcium-transporting ATPase 3 isoform X2

      UniProtKB/TrEMBL
      A0A994J5M1
      Related
      ENSP00000516173.1, ENST00000496610.2
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1175
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    2. XM_024452386.2 → XP_024308154.1  plasma membrane calcium-transporting ATPase 3 isoform X6

      Related
      ENSP00000359205.1, ENST00000370186.5
      Conserved Domains (2) summary
      pfam12424
      Location:1086 → 1131
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
      cl27747
      Location:27 → 1047
      E1-E2_ATPase; E1-E2 ATPase

    3. XM_005274691.4 → XP_005274748.1  plasma membrane calcium-transporting ATPase 3 isoform X4

      See identical proteins and their annotated locations for XP_005274748.1

      UniProtKB/Swiss-Prot
      Q16720
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1047
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1086 → 1132
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    4. XM_047442141.1 → XP_047298097.1  plasma membrane calcium-transporting ATPase 3 isoform X5

      Related
      ENSP00000516174.1, ENST00000705862.1
      Conserved Domains (2) summary
      TIGR01517
      Location:27 → 1061
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam12424
      Location:1100 → 1140
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

    5. XM_011531177.3 → XP_011529479.1  plasma membrane calcium-transporting ATPase 3 isoform X3

      Conserved Domains (7) summary
      TIGR01517
      Location:27 → 1047
      ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
      pfam00122
      Location:164 → 448
      E1-E2_ATPase; E1-E2 ATPase
      pfam00689
      Location:863 → 1041
      Cation_ATPase_C; Cation transporting ATPase, C-terminus
      pfam00690
      Location:51 → 121
      Cation_ATPase_N; Cation transporter/ATPase, N-terminus
      pfam12424
      Location:1086 → 1100
      ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
      pfam12710
      Location:670 → 789
      HAD; haloacid dehalogenase-like hydrolase
      pfam13246
      Location:509 → 598
      Cation_ATPase; Cation transport ATPase (P-type)

    6. XM_047442142.1 → XP_047298098.1  plasma membrane calcium-transporting ATPase 3 isoform X7

      Related
      ENSP00000377425.1, ENST00000393842.5

    7. XM_017029553.2 → XP_016885042.1  plasma membrane calcium-transporting ATPase 3 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      151791198..151856492
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327132.1 → XP_054183107.1  plasma membrane calcium-transporting ATPase 3 isoform X2

      UniProtKB/TrEMBL
      A0A994J5M1

    2. XM_054327135.1 → XP_054183110.1  plasma membrane calcium-transporting ATPase 3 isoform X6

    3. XM_054327134.1 → XP_054183109.1  plasma membrane calcium-transporting ATPase 3 isoform X4

    4. XM_054327133.1 → XP_054183108.1  plasma membrane calcium-transporting ATPase 3 isoform X3

    5. XM_054327136.1 → XP_054183111.1  plasma membrane calcium-transporting ATPase 3 isoform X7

    6. XM_054327131.1 → XP_054183106.1  plasma membrane calcium-transporting ATPase 3 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16720.3 GenPept UniProtKB/Swiss-Prot:Q16720

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