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

Gene ID: 493, updated on 10-Nov-2018

Summary

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; Vega:OTTHUMG00000035906
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

Genomic context

See ATP2B4 in Genome Data Viewer
Location:
1q32.1
Exon count:
22
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (203626787..203744081)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (203595915..203713209)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371688 Neighboring gene proline and arginine rich end leucine rich repeat protein Neighboring gene opticin Neighboring gene NSA2 ribosome biogenesis homolog (S. cerevisiae) pseudogene Neighboring gene uncharacterized LOC102723543 Neighboring gene long intergenic non-protein coding RNA 260 Neighboring gene small nucleolar RNA, H/ACA box 77 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

Expression

  • 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

Pathways from BioSystems

  • Adrenergic signaling in cardiomyocytes, organism-specific biosystem (from KEGG)
    Adrenergic signaling in cardiomyocytes, organism-specific biosystemCardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, a...
  • Adrenergic signaling in cardiomyocytes, conserved biosystem (from KEGG)
    Adrenergic signaling in cardiomyocytes, conserved biosystemCardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, a...
  • Calcium signaling pathway, organism-specific biosystem (from KEGG)
    Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
  • Calcium signaling pathway, conserved biosystem (from KEGG)
    Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
  • Cardiac conduction, organism-specific biosystem (from REACTOME)
    Cardiac conduction, organism-specific biosystemThe normal sequence of contraction of atria and ventricles of the heart require activation of groups of cardiac cells. The mechanism must elicit rapid changes in heart rate and respond to changes in ...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Ion channel transport, organism-specific biosystem (from REACTOME)
    Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
  • Ion homeostasis, organism-specific biosystem (from REACTOME)
    Ion homeostasis, organism-specific biosystemIon channel homeostasis in relation to cardiac conduction is described in this section (Couette et al. 2006, Bartos et al. 2015).
  • Ion transport by P-type ATPases, organism-specific biosystem (from REACTOME)
    Ion transport by P-type ATPases, organism-specific biosystemThe P-type ATPases (E1-E2 ATPases) are a large group of evolutionarily related ion pumps that are found in bacteria, archaea and eukaryotes. They are referred to as P-type ATPases because they catal...
  • Muscle contraction, organism-specific biosystem (from REACTOME)
    Muscle contraction, organism-specific biosystemIn this module, the processes by which calcium binding triggers actin - myosin interactions and force generation in smooth and striated muscle tissues are annotated.
  • Pancreatic secretion, organism-specific biosystem (from KEGG)
    Pancreatic secretion, organism-specific biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
  • Pancreatic secretion, conserved biosystem (from KEGG)
    Pancreatic secretion, conserved biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
  • Platelet calcium homeostasis, organism-specific biosystem (from REACTOME)
    Platelet calcium homeostasis, organism-specific biosystemCa2+ homeostasis is controlled by processes that elevate or counter the elevation of cytosolic Ca2+. During steady state conditions, cytoplasmic Ca2+ is reduced by the accumulation of Ca2+ in intrac...
  • Platelet homeostasis, organism-specific biosystem (from REACTOME)
    Platelet homeostasis, organism-specific biosystemUnder normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in charact...
  • Reduction of cytosolic Ca++ levels, organism-specific biosystem (from REACTOME)
    Reduction of cytosolic Ca++ levels, organism-specific biosystemDuring steady state conditions, cytoplasmic [Ca2+] is reduced by the accumulation of Ca2+ in intracellular stores and Ca2+ extrusion.
  • Salivary secretion, organism-specific biosystem (from KEGG)
    Salivary secretion, organism-specific biosystemSaliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for e...
  • Salivary secretion, conserved biosystem (from KEGG)
    Salivary secretion, conserved biosystemSaliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for e...
  • Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
    Transmembrane transport of small molecules, organism-specific biosystem
    Transmembrane transport of small molecules
  • cAMP signaling pathway, organism-specific biosystem (from KEGG)
    cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
  • cAMP signaling pathway, conserved biosystem (from KEGG)
    cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
  • cGMP-PKG signaling pathway, organism-specific biosystem (from KEGG)
    cGMP-PKG signaling pathway, organism-specific biosystemCyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated i...
  • cGMP-PKG signaling pathway, conserved biosystem (from KEGG)
    cGMP-PKG signaling pathway, conserved biosystemCyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated i...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp686M088, DKFZp686G08106

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
PDZ domain binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
calcium-transporting ATPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
calcium-transporting ATPase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
calcium-transporting ATPase activity TAS
Traceable Author Statement
more info
 
calmodulin binding IDA
Inferred from Direct Assay
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
nitric-oxide synthase binding IPI
Inferred from Physical Interaction
more info
PubMed 
nitric-oxide synthase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to nitric-oxide synthase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IEA
Inferred from Electronic Annotation
more info
 
protein phosphatase 2B binding IDA
Inferred from Direct Assay
more info
PubMed 
scaffold protein binding ISS
Inferred from Sequence or Structural Similarity
more info
 
contributes_to sodium channel regulator activity ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
ATP hydrolysis coupled cation transmembrane transport IEA
Inferred from Electronic Annotation
more info
 
calcium ion export IEA
Inferred from Electronic Annotation
more info
 
calcium ion import across plasma membrane IC
Inferred by Curator
more info
PubMed 
calcium ion transmembrane import into cytosol IC
Inferred by Curator
more info
PubMed 
calcium ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular calcium ion homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular calcium ion homeostasis IC
Inferred by Curator
more info
PubMed 
cellular calcium ion homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
cellular calcium ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to epinephrine stimulus IDA
Inferred from Direct Assay
more info
PubMed 
flagellated sperm motility ISS
Inferred from Sequence or Structural Similarity
more info
 
hippocampus development IEA
Inferred from Electronic Annotation
more info
 
ion transmembrane transport TAS
Traceable Author Statement
more info
 
negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of arginine catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of calcineurin-NFAT signaling cascade IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cardiac muscle hypertrophy in response to stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of citrulline biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of nitric oxide biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of nitric oxide mediated signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of nitric-oxide synthase activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of peptidyl-cysteine S-nitrosylation NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of the force of heart contraction IDA
Inferred from Direct Assay
more info
PubMed 
neural retina development IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cAMP-dependent protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cardiac conduction TAS
Traceable Author Statement
more info
 
regulation of cell cycle G1/S phase transition IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cytosolic calcium ion concentration IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of sodium ion transmembrane transport IC
Inferred by Curator
more info
PubMed 
regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to hydrostatic pressure IMP
Inferred from Mutant Phenotype
more info
PubMed 
spermatogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
T-tubule IDA
Inferred from Direct Assay
more info
PubMed 
Z disc IDA
Inferred from Direct Assay
more info
PubMed 
basolateral plasma membrane IEA
Inferred from Electronic Annotation
more info
 
caveola TAS
Traceable Author Statement
more info
PubMed 
glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of presynaptic active zone membrane IEA
Inferred from Electronic Annotation
more info
 
membrane HDA PubMed 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
neuron projection IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
protein-containing complex ISS
Inferred from Sequence or Structural Similarity
more info
 
sperm flagellum ISS
Inferred from Sequence or Structural Similarity
more info
 
sperm principal piece IEA
Inferred from Electronic Annotation
more info
 

General protein information

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_001675.3

NCBI Reference Sequences (RefSeq)

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
    5001..122295
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001001396.2NP_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, BX537444, DN997129, M83363
    Consensus CDS
    CCDS30977.1
    UniProtKB/Swiss-Prot
    P23634
    Related
    ENSP00000356187.3, ENST00000367218.7
    Conserved Domains (7) summary
    TIGR01517
    Location:201052
    ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
    pfam00122
    Location:153454
    E1-E2_ATPase; E1-E2 ATPase
    pfam00689
    Location:8681049
    Cation_ATPase_C; Cation transporting ATPase, C-terminus
    pfam00690
    Location:47111
    Cation_ATPase_N; Cation transporter/ATPase, N-terminus
    pfam12424
    Location:10891151
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    pfam12710
    Location:655794
    HAD; haloacid dehalogenase-like hydrolase
    pfam13246
    Location:515604
    Cation_ATPase; Cation transport ATPase (P-type)
  2. NM_001365783.1NP_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
    Conserved Domains (2) summary
    pfam12424
    Location:10891150
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    cl27747
    Location:201052
    E1-E2_ATPase; E1-E2 ATPase
  3. NM_001365784.1NP_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
    Conserved Domains (2) summary
    pfam12424
    Location:10891150
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    cl27747
    Location:201052
    E1-E2_ATPase; E1-E2 ATPase
  4. NM_001684.4NP_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, BX537444, DN997129, M25874
    Consensus CDS
    CCDS1440.1
    UniProtKB/Swiss-Prot
    P23634
    UniProtKB/TrEMBL
    A0A024R968
    Related
    ENSP00000350310.5, OTTHUMP00000034088, ENST00000357681.9, OTTHUMT00000087462
    Conserved Domains (7) summary
    TIGR01517
    Location:201052
    ATPase-IIB_Ca; plasma-membrane calcium-translocating P-type ATPase
    pfam00122
    Location:153454
    E1-E2_ATPase; E1-E2 ATPase
    pfam00689
    Location:8681049
    Cation_ATPase_C; Cation transporting ATPase, C-terminus
    pfam00690
    Location:47111
    Cation_ATPase_N; Cation transporter/ATPase, N-terminus
    pfam12424
    Location:10891136
    ATP_Ca_trans_C; Plasma membrane calcium transporter ATPase C terminal
    pfam12710
    Location:655794
    HAD; haloacid dehalogenase-like hydrolase
    pfam13246
    Location:515604
    Cation_ATPase; Cation transport ATPase (P-type)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 Primary Assembly

    Range
    203626787..203744081
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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