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ATP2B4 ATPase plasma membrane Ca2+ transporting 4 [ Homo sapiens (human) ]

Gene ID: 493, updated on 2-Nov-2024

Summary

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Official Symbol
ATP2B4provided by HGNC
Official Full Name
ATPase plasma membrane Ca2+ transporting 4provided by HGNC
Primary source
HGNC:HGNC:817
See related
Ensembl:ENSG00000058668 MIM:108732; AllianceGenome:HGNC:817
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
MXRA1; PMCA4; ATP2B2; PMCA4b; PMCA4x
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 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in endometrium (RPKM 66.6), fat (RPKM 45.1) and 23 other tissues See more
Orthologs
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Genomic context

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See ATP2B4 in Genome Data Viewer
Location:
1q32.1
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (203626832..203744081)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (202890048..203007281)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (203595960..203713209)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371688 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:203473836-203474011 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:203480878-203481618 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:203481606-203482805 Neighboring gene uncharacterized LOC124904488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203486279-203487110 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203487943-203488774 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203488775-203489607 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203491273-203492103 Neighboring gene opticin Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203525277-203526201 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:203526215-203526792 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203541106-203541988 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1721 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:203569376-203569876 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:203569877-203570377 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:203594954-203595828 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:203595829-203596701 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1722 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1723 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:203598915-203599601 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1724 Neighboring gene NSA2 pseudogene 1 Neighboring gene uncharacterized LOC102723543 Neighboring gene long intergenic non-protein coding RNA 260 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:203722055-203722656 Neighboring gene small nucleolar RNA, H/ACA box 77 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2354 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2355 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:203741871-203742446 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2356 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2357 Neighboring gene uncharacterized LOC128031836 Neighboring gene lymphocyte transmembrane adaptor 1 Neighboring gene zinc finger CCCH-type containing 11A Neighboring gene zinc finger BED-type containing 6

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. Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism. Hattangady NG, et al. Horm Cancer, 2020 Feb. PMID 32002807, Free PMC Article
  2. Loss of autoinhibition of the plasma membrane Ca(2+) pump by substitution of aspartic 170 by asparagin. A ctivation of plasma membrane calcium ATPase 4 without disruption of the interaction between the catalytic core and the C-terminal regulatory domain. Bredeston LM, et al. J Biol Chem, 2004 Oct 1. PMID 15292209
  3. Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative quantification of polytopic membrane proteins. Calcagno AM, et al. BMC Mol Biol, 2006 Sep 17. PMID 16978418, Free PMC Article
  4. Plasma membrane Ca(2+) -ATPase associates with CLP36, alpha-actinin and actin in human platelets. Bozulic LD, et al. Thromb Haemost, 2007 Apr. PMID 17393022
  5. Platelet PMCA- and SERCA-type Ca2+ -ATPase expression in diabetes: a novel signature of abnormal megakaryocytopoiesis. Chaabane C, et al. J Thromb Haemost, 2007 Oct. PMID 17883705

See all (163) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Mammalian cysteine-rich secretory proteins interact with plasma membrane Ca[2+] exporter PMCA4b.
    Title: Mammalian cysteine-rich secretory proteins interact with plasma membrane Ca(2+) exporter PMCA4b.
  2. ATP2B4 is an essential gene for epidermal growth factor-induced macropinocytosis in A431 cells.
    Title: ATP2B4 is an essential gene for epidermal growth factor-induced macropinocytosis in A431 cells.
  3. ATP2B4 regulatory genetic variants are associated with mild malaria.
    Title: ATP2B4 regulatory genetic variants are associated with mild malaria.
  4. Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults.
    Title: Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults.
  5. Identification of ATP2B4 Regulatory Element Containing Functional Genetic Variants Associated with Severe Malaria.
    Title: Identification of ATP2B4 Regulatory Element Containing Functional Genetic Variants Associated with Severe Malaria.
  6. Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation.
    Title: Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation.
  7. Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip.
    Title: Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip.
  8. Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4(+) T-Cell Compartments.
    Title: Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4(+) T-Cell Compartments.
  9. P38 MAPK Promotes Migration and Metastatic Activity of BRAF Mutant Melanoma Cells by Inducing Degradation of PMCA4b.
    Title: P38 MAPK Promotes Migration and Metastatic Activity of BRAF Mutant Melanoma Cells by Inducing Degradation of PMCA4b.
  10. The calcium pump PMCA4 prevents epithelial-mesenchymal transition by inhibiting NFATc1-ZEB1 pathway in gastric cancer.
    Title: The calcium pump PMCA4 prevents epithelial-mesenchymal transition by inhibiting NFATc1-ZEB1 pathway in gastric cancer.
Submit: New GeneRIF Correction See all GeneRIFs (69)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic variants associated with breast size also influence breast cancer risk.
EBI GWAS Catalog
Genome-wide association study indicates two novel resistance loci for severe malaria.
EBI GWAS Catalog
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
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

Clone Names

  • DKFZp686M088, DKFZp686G08106

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 IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables P-type calcium transporter activity TAS
Traceable Author Statement
more info
  
enables calcium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables calmodulin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables nitric-oxide synthase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables nitric-oxide synthase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IEA
Inferred from Electronic Annotation
more info
  
enables protein phosphatase 2B binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein phosphatase 2B binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein phosphatase 2B binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables scaffold protein binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables sodium channel regulator activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in calcium ion export IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in calcium ion import across plasma membrane IC
Inferred by Curator
more info
 PubMed 
involved_in calcium ion transmembrane import into cytosol IC
Inferred by Curator
more info
 PubMed 
involved_in calcium ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to acetylcholine ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to epinephrine stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in flagellated sperm motility ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in hippocampus development IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular calcium ion homeostasis IC
Inferred by Curator
more info
 PubMed 
involved_in intracellular calcium ion homeostasis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in intracellular calcium ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in monoatomic ion transmembrane transport TAS
Traceable Author Statement
more info
  
involved_in negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of angiogenesis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of arginine catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of blood vessel endothelial cell migration IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of calcineurin-NFAT signaling cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of calcineurin-NFAT signaling cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cardiac muscle hypertrophy in response to stress IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cellular response to vascular endothelial growth factor stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of citrulline biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of gene expression IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of nitric oxide biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of nitric-oxide synthase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of peptidyl-cysteine S-nitrosylation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of the force of heart contraction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in neural retina development IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_negative_effect nitric oxide-cGMP-mediated signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of protein localization to plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cardiac conduction TAS
Traceable Author Statement
more info
  
involved_in regulation of cell cycle G1/S phase transition IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of cytosolic calcium ion concentration IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of sodium ion transmembrane transport IC
Inferred by Curator
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to hydrostatic pressure IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in spermatogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in transport across blood-brain barrier NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in urinary bladder smooth muscle contraction ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in T-tubule IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Z disc IDA
Inferred from Direct Assay
more info
 PubMed 
located_in basolateral plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in caveola TAS
Traceable Author Statement
more info
 PubMed 
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in intracellular membrane-bounded organelle IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane HDA PubMed 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane raft IDA
Inferred from Direct Assay
more info
 PubMed 
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
  
located_in plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in presynaptic active zone membrane IEA
Inferred from Electronic Annotation
more info
  
part_of protein-containing complex ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in sperm flagellum ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in sperm principal piece IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
plasma membrane calcium-transporting ATPase 4
Names
ATPase, Ca++ transporting, plasma membrane 4
matrix-remodeling-associated protein 1
sarcolemmal calcium pump
NP_001001396.1
NP_001352712.1
NP_001352713.1
NP_001675.3

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_029589.1 RefSeqGene

    Range
    5046..122295
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001001396.3 → NP_001001396.1  plasma membrane calcium-transporting ATPase 4 isoform 4a

    See identical proteins and their annotated locations for NP_001001396.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the shorter isoform (4a).
    Source sequence(s)
    AC114402, AL706212, AW888226, BF985985, DN997129, M83363
    Consensus CDS
    CCDS30977.1
    UniProtKB/TrEMBL
    A7E2D8
    Related
    ENSP00000340930.2, ENST00000341360.7
    Conserved Domains (7) summary
    TIGR01517
    Location:20 → 1052
    ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
    pfam00122
    Location:153 → 454
    E1-E2_ATPase; E1-E2 ATPase
    pfam00689
    Location:868 → 1049
    Cation_ATPase_C; Cation transporting ATPase, C-terminus
    pfam00690
    Location:47 → 111
    Cation_ATPase_N; Cation transporter/ATPase, N-terminus
    pfam12424
    Location:1089 → 1151
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    pfam12710
    Location:655 → 794
    HAD; haloacid dehalogenase-like hydrolase
    pfam13246
    Location:515 → 604
    Cation_ATPase; Cation transport ATPase (P-type)

  2. NM_001365783.2 → NP_001352712.1  plasma membrane calcium-transporting ATPase 4 isoform 4c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), as well as variant 4, encodes isoform 4c.
    Source sequence(s)
    AC114402, AL513343
    UniProtKB/TrEMBL
    A7E2D8
    Conserved Domains (2) summary
    pfam12424
    Location:1089 → 1150
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    cl27747
    Location:20 → 1052
    E1-E2_ATPase; E1-E2 ATPase

  3. NM_001365784.2 → NP_001352713.1  plasma membrane calcium-transporting ATPase 4 isoform 4c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variant 3, encodes isoform 4c.
    Source sequence(s)
    AC114402, AL513343
    UniProtKB/TrEMBL
    A7E2D8
    Conserved Domains (2) summary
    pfam12424
    Location:1089 → 1150
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    cl27747
    Location:20 → 1052
    E1-E2_ATPase; E1-E2 ATPase

  4. NM_001684.5 → NP_001675.3  plasma membrane calcium-transporting ATPase 4 isoform 4b

    See identical proteins and their annotated locations for NP_001675.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate coding exon compared to variant 1, that causes a frameshift. The resulting isoform (4b) has a longer and distinct C-terminus compared to isoform 4a.
    Source sequence(s)
    AC114402, AL706212, AW888226, BF985985, DN997129, M25874
    Consensus CDS
    CCDS1440.1
    UniProtKB/TrEMBL
    Q68DH9
    Related
    ENSP00000350310.5, ENST00000357681.10
    Conserved Domains (2) summary
    TIGR01517
    Location:20 → 1052
    ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
    pfam12424
    Location:1089 → 1135
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    203626832..203744081
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    202890048..203007281
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P23634.2 GenPept UniProtKB/Swiss-Prot:P23634

Gene LinkOut

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