Gene description for ATP2B4
Gene name ATPase, Ca++ transporting, plasma membrane 4
Gene symbol ATP2B4
Other names/aliases ATP2B2
MXRA1
PMCA4
PMCA4b
PMCA4x
Species Homo sapiens
 Database cross references - ATP2B4
ExoCarta ExoCarta_493
Entrez Gene 493
HGNC 817
MIM 108732
UniProt P23634  
 ATP2B4 identified in exosomes derived from the following tissue/cell type
Bladder cancer cells 20224111    
Colorectal cancer cells 23161513    
Colorectal cancer cells 23161513    
Colorectal cancer cells 23161513    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Mesenchymal stem cells Unpublished / Not applicable
Neuroblastoma cells 25944692    
Ovarian cancer cells 23333927    
Ovarian cancer cells 23333927    
Platelets 25332113    
Platelets 25332113    
Platelets 25332113    
Prostate cancer cells 25844599    
Thymus 23844026    
 Gene ontology annotations for ATP2B4
Molecular Function
    sodium channel regulator activity GO:0017080 ISS
    calcium-transporting ATPase activity GO:0005388 IMP
    protein binding GO:0005515 IPI
    calmodulin binding GO:0005516 IDA
    metal ion binding GO:0046872 IEA
    ATP binding GO:0005524 IEA
    nitric-oxide synthase inhibitor activity GO:0036487 IDA
    nitric-oxide synthase binding GO:0050998 IPI
    protein phosphatase 2B binding GO:0030346 IDA
    scaffold protein binding GO:0097110 ISS
Biological Process
    negative regulation of peptidyl-cysteine S-nitrosylation GO:1902083 NAS
    negative regulation of calcineurin-NFAT signaling cascade GO:0070885 IDA
    ion transmembrane transport GO:0034220 TAS
    transmembrane transport GO:0055085 TAS
    regulation of sodium ion transmembrane transport GO:1902305 IC
    cellular calcium ion homeostasis GO:0006874 IDA
    regulation of cell cycle G1/S phase transition GO:1902806 IMP
    negative regulation of nitric oxide biosynthetic process GO:0045019 IDA
    response to hydrostatic pressure GO:0051599 IMP
    negative regulation of arginine catabolic process GO:1900082 IDA
    calcium ion import across plasma membrane GO:0098703 IC
    metabolic process GO:0008152 IEA
    regulation of transcription from RNA polymerase II promoter GO:0006357 IMP
    blood coagulation GO:0007596 TAS
    positive regulation of cAMP-dependent protein kinase activity GO:2000481 IDA
    negative regulation of adrenergic receptor signaling pathway involved in heart process GO:1901205 IDA
    negative regulation of nitric oxide mediated signal transduction GO:0010751 IDA
    positive regulation of peptidyl-serine phosphorylation GO:0033138 IDA
    cellular response to epinephrine stimulus GO:0071872 IDA
    calcium ion transmembrane import into cytosol GO:0097553 IC
    negative regulation of the force of heart contraction GO:0098736 IDA
    negative regulation of cardiac muscle hypertrophy in response to stress GO:1903243 IMP
    negative regulation of citrulline biosynthetic process GO:1903249 IDA
    calcium ion transmembrane transport GO:0070588 IMP
    negative regulation of nitric-oxide synthase activity GO:0051001 IDA
Subcellular Localization
    Z disc GO:0030018 IDA
    integral component of plasma membrane GO:0005887 TAS
    T-tubule GO:0030315 IDA
    membrane GO:0016020 IDA
    protein complex GO:0043234 ISS
    plasma membrane GO:0005886 TAS
    caveola GO:0005901 TAS
 Experiment description of studies that identified ATP2B4 in exosomes
1
Experiment ID 76
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|GAPDH|HSP90
EV Cytosolic markers
✔
CD81|CD9|CD63|LAMP1|MHCI
EV Membrane markers
✔
HSP90B1
EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 20224111    
Organism Homo sapiens
Experiment description Proteomics analysis of bladder cancer exosomes.
Authors Welton JL, Khanna S, Giles PJ, Brennan P, Brewis IA, Staffurth J, Mason MD, Clayton A.
Journal name MCP
Publication year 2010
Sample Bladder cancer cells
Sample name HT1376
Isolation/purification methods Differential centrifugation
Sucrose density gradient
Flotation density 1.10-1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry [MALDI TOF/TOF]
Western blotting
FACS
2
Experiment ID 207
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|HSP70
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name DKO-1
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
3
Experiment ID 208
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|HSP70
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name Dks-8
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
4
Experiment ID 209
ISEV standards
✘ EV Biophysical techniques
✔
TSG101|HSP70
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name DLD-1
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
5
Experiment ID 255
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name G1
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
6
Experiment ID 256
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name 501mel
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
7
Experiment ID 257
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name Daju
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
8
Experiment ID 258
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1|CD81
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name SKMEL28
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
9
Experiment ID 259
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name A375M
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
10
Experiment ID 260
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1|CD81
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name 1205Lu
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
11
Experiment ID 126
ISEV standards
✘ EV Biophysical techniques
✔
GAPDH
EV Cytosolic markers
✘ EV Membrane markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry [LTQ-FT Ultra]
PubMed ID Unpublished / Not applicable
Organism Homo sapiens
Experiment description Mesenchymal Stem Cell Exosomes: The Future MSC-based Therapy?
Authors Ruenn Chai Lai, Ronne Wee Yeh Yeo, Soon Sim Tan, Bin Zhang, Yijun Yin, Newman Siu Kwan Sze, Andre Choo, and Sai Kiang Lim
Journal name Mesenchymal Stem Cell Therapy
Publication year 2011
Sample Mesenchymal stem cells
Sample name huES9.E1
Isolation/purification methods HPLC
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Antobody array
Mass spectrometry
12
Experiment ID 224
ISEV standards
✔
EM|AFM
EV Biophysical techniques
✔
Alix|TSG101
EV Cytosolic markers
✔
CD63|CD81
EV Membrane markers
✔
GOLGA2
EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25944692    
Organism Homo sapiens
Experiment description Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes
Authors Keerthikumar S, Gangoda L, Liem M, Fonseka P, Atukorala I, Ozcitti C, Mechler A, Adda CG, Ang CS, Mathivanan S
Journal name Oncotarget
Publication year 2015
Sample Neuroblastoma cells
Sample name SH-SY5Y
Isolation/purification methods Differential centrifugation
Ultracentrifugation
OptiPrep density gradient
Flotation density 1.10 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
Western blotting
13
Experiment ID 211
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix
EV Cytosolic markers
✔
EpCAM|TFRC
EV Membrane markers
✔
cytochrome c|GOLGA2
EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23333927    
Organism Homo sapiens
Experiment description Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Authors Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K.
Journal name J Proteomics
Publication year 2013
Sample Ovarian cancer cells
Sample name IGROV1
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Sucrose density gradient
Flotation density 1.09-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
14
Experiment ID 212
ISEV standards
✔
CEM
EV Biophysical techniques
✔
TSG101|Alix
EV Cytosolic markers
✔
EpCAM|TFRC
EV Membrane markers
✔
Cytochrome C|GOLGA2
EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23333927    
Organism Homo sapiens
Experiment description Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Authors Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K.
Journal name J Proteomics
Publication year 2013
Sample Ovarian cancer cells
Sample name OVCAR-3
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Sucrose density gradient
Flotation density 1.09-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
15
Experiment ID 231
ISEV standards
✘ EV Biophysical techniques
✔
Alix
EV Cytosolic markers
✔
CD63|CD9
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25332113    
Organism Homo sapiens
Experiment description Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors Pienimaeki-Roemer A, Kuhlmann K, Bottcher A, Konovalova T, Black A, Orso E, Liebisch G, Ahrens M, Eisenacher M, Meyer HE, Schmitz G.
Journal name Transfusion
Publication year 2015
Sample Platelets
Sample name PL-Exs - Rep 1
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Optiprep density gradient
Flotation density 1.12-1.15 g/mL
Molecules identified in the study Protein
Lipids
Methods used in the study Western blotting
Mass spectrometry
16
Experiment ID 232
ISEV standards
✘ EV Biophysical techniques
✘ EV Cytosolic markers
✘ EV Membrane markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25332113    
Organism Homo sapiens
Experiment description Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors Pienimaeki-Roemer A, Kuhlmann K, Bottcher A, Konovalova T, Black A, Orso E, Liebisch G, Ahrens M, Eisenacher M, Meyer HE, Schmitz G.
Journal name Transfusion
Publication year 2015
Sample Platelets
Sample name PL-Exs - Rep 2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Optiprep density gradient
Flotation density 1.12-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
17
Experiment ID 233
ISEV standards
✘ EV Biophysical techniques
✘ EV Cytosolic markers
✘ EV Membrane markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25332113    
Organism Homo sapiens
Experiment description Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors Pienimaeki-Roemer A, Kuhlmann K, Bottcher A, Konovalova T, Black A, Orso E, Liebisch G, Ahrens M, Eisenacher M, Meyer HE, Schmitz G.
Journal name Transfusion
Publication year 2015
Sample Platelets
Sample name PL-Exs - Rep 3
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Optiprep density gradient
Flotation density 1.12-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
18
Experiment ID 275
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix|RAB5A
EV Cytosolic markers
✔
CD9|CD82|CD63|CD81
EV Membrane markers
✔
AIF
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25844599    
Organism Homo sapiens
Experiment description Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.
Authors Kharaziha P, Chioureas D, Rutishauser D, Baltatzis G, Lennartsson L, Fonseca P, Azimi A, Hultenby K, Zubarev R, Ullen A, Yachnin J, Nilsson S, Panaretakis T.
Journal name Oncotarget
Publication year 2015
Sample Prostate cancer cells
Sample name DU145 - Docetaxel sensitive
Isolation/purification methods Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.12-1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry/Flow cytometry/Western blotting
19
Experiment ID 217
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
CD81|CD9|CD63
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23844026    
Organism Homo sapiens
Experiment description Characterization of human thymic exosomes.
Authors Skogberg G, Gudmundsdottir J, van der Post S, Sandstrom K, Bruhn S, Benson M, Mincheva-Nilsson L, Baranov V, Telemo E, Ekwall O.
Journal name PLoS One
Publication year 2013
Sample Thymus
Sample name Normal-Thymus
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
 Protein-protein interactions for ATP2B4
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 DLG1 1739
Invitro Homo sapiens
Reconstituted Complex Homo sapiens
2 DLG4  
Invitro Homo sapiens
3 DLG2 1740
Invitro Homo sapiens
Invivo Homo sapiens
4 DLG3 1741
Invitro Homo sapiens
Invivo Homo sapiens
Two-hybrid Homo sapiens
5 CASK 8573
Reconstituted Complex Homo sapiens
Co-fractionation Homo sapiens
View the network image/svg+xml
 Pathways in which ATP2B4 is involved
PathwayEvidenceSource
Ion transport by P-type ATPases TAS Reactome
Reduction of cytosolic Ca++ levels TAS Reactome





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