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

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; 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: mouse all
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Genomic context

Location:: 1q32.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (203626832..203744081)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (202890048..203007281)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (203595960..203713209)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ATP2B4 regulatory genetic variants are associated with mild malaria.
Title: ATP2B4 regulatory genetic variants are associated with mild malaria.
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.
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.
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.
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.
Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4(+) T-Cell Compartments.
Title: Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4(+) T-Cell Compartments.
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.
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.
CircATP2B4 promotes hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells via the miR-223/ATR axis.
Title: CircATP2B4 promotes hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells via the miR-223/ATR axis.
Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism.
Title: Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism.

Submit: New GeneRIF Correction See all GeneRIFs (67)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-76189 (e-PCR)
- UniSTS:60416

RH64645 (e-PCR)
- UniSTS:50450

D1S387 (e-PCR)
- UniSTS:5145

RH63844 (e-PCR)
- UniSTS:32820

SHGC-76187 (e-PCR)
- UniSTS:40760

RH64618 (e-PCR)
- UniSTS:32646

SHGC-76196 (e-PCR)
- UniSTS:40587

G19696 (e-PCR)
- UniSTS:35497

A001V38 (e-PCR)
- UniSTS:35498

SHGC-56960 (e-PCR)
- UniSTS:23229

D1S510 (e-PCR), detects polymorphism
- UniSTS:3008

D1S2376 (e-PCR)
- UniSTS:46530

D1S510 (e-PCR), detects polymorphism
- UniSTS:78548

AL034138 (e-PCR)
- UniSTS:93909

SHGC-12393 (e-PCR)
- UniSTS:53756

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 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	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 more info	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

EC 7.2.2.10

NP_001352712.1

EC 7.2.2.10

NP_001352713.1

EC 7.2.2.10

NP_001675.3

EC 7.2.2.10

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

NG_029589.1 RefSeqGene

Range

5046..122295

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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)
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
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
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