ATP2B4 (ATPase plasma membrane Ca2+ transporting 4)

Gene

• Entrez ID: 493
• Gene name: ATPase plasma membrane Ca2+ transporting 4
• Gene symbol: ATP2B4
• Synonyms: ATP2B2, MXRA1, PMCA4, PMCA4b, PMCA4x
• Chromosome: 1
• Chromosome location: 1q32.1
• 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017163	hsa-miR-335-5p	Microarray	18185580
MIRT023603	hsa-miR-1-3p	Proteomics	18668040
MIRT030786	hsa-miR-21-5p	Microarray	18591254
MIRT038088	hsa-miR-423-5p	CLASH	23622248
MIRT061739	hsa-miR-32-5p	HITS-CLIP	22473208
MIRT061740	hsa-miR-92a-3p	HITS-CLIP	22473208
MIRT061743	hsa-miR-92b-3p	HITS-CLIP	22473208
MIRT061744	hsa-miR-1277-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT061748	hsa-miR-5011-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT183578	hsa-miR-190a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT441149	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT496377	hsa-miR-6806-5p	PAR-CLIP	22291592
MIRT496378	hsa-miR-4290	PAR-CLIP	22291592
MIRT496379	hsa-miR-488-5p	PAR-CLIP	22291592
MIRT496380	hsa-miR-4747-3p	PAR-CLIP	22291592
MIRT559365	hsa-miR-6083	PAR-CLIP	21572407
MIRT712572	hsa-miR-642a-5p	HITS-CLIP	19536157
MIRT712573	hsa-miR-452-3p	HITS-CLIP	19536157
MIRT712574	hsa-miR-7106-3p	HITS-CLIP	19536157
MIRT712575	hsa-miR-6886-3p	HITS-CLIP	19536157
MIRT712576	hsa-miR-938	HITS-CLIP	19536157
MIRT712577	hsa-miR-18a-3p	HITS-CLIP	19536157
MIRT712578	hsa-miR-7113-3p	HITS-CLIP	19536157
MIRT712579	hsa-miR-6734-3p	HITS-CLIP	19536157
MIRT712580	hsa-miR-6891-3p	HITS-CLIP	19536157
MIRT712581	hsa-miR-6072	HITS-CLIP	19536157
MIRT712582	hsa-miR-6752-3p	HITS-CLIP	19536157

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003407	Process	Neural retina development	IEA
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IBA	21873635
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IMP	8530416
GO:0005515	Function	Protein binding	IPI	17242280, 17689535, 22084111, 25906147
GO:0005516	Function	Calmodulin binding	IDA	8530416
GO:0005524	Function	ATP binding	IEA
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Component	Integral component of plasma membrane	NAS	15955804
GO:0005901	Component	Caveola	TAS	11591728
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IMP	19287093
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0006874	Process	Cellular calcium ion homeostasis	IC	8530416
GO:0006874	Process	Cellular calcium ion homeostasis	IDA	19278978, 25798335
GO:0006874	Process	Cellular calcium ion homeostasis	ISS
GO:0007283	Process	Spermatogenesis	IEA
GO:0010629	Process	Negative regulation of gene expression	IDA	25147342
GO:0010751	Process	Negative regulation of nitric oxide mediated signal transduction	IDA	19278978
GO:0014832	Process	Urinary bladder smooth muscle contraction	ISS
GO:0015085	Function	Calcium ion transmembrane transporter activity	IDA	23549614
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IDA	8530416, 23549614, 25147342
GO:0016323	Component	Basolateral plasma membrane	IEA
GO:0016525	Process	Negative regulation of angiogenesis	IDA	25147342
GO:0017080	Function	Sodium channel regulator activity	ISS
GO:0019829	Function	ATPase-coupled cation transmembrane transporter activity	IBA	21873635
GO:0019901	Function	Protein kinase binding	IEA
GO:0021766	Process	Hippocampus development	IEA
GO:0030018	Component	Z disc	IDA	19287093
GO:0030165	Function	PDZ domain binding	IBA	21873635
GO:0030315	Component	T-tubule	IDA	19287093
GO:0030317	Process	Flagellated sperm motility	ISS
GO:0030346	Function	Protein phosphatase 2B binding	IDA	19287093
GO:0030346	Function	Protein phosphatase 2B binding	IMP	25147342
GO:0030346	Function	Protein phosphatase 2B binding	IPI	15955804
GO:0032991	Component	Protein-containing complex	ISS
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	IDA	19278978
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0036126	Component	Sperm flagellum	ISS
GO:0036487	Function	Nitric-oxide synthase inhibitor activity	IDA	11591728, 17242280
GO:0043005	Component	Neuron projection	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0043537	Process	Negative regulation of blood vessel endothelial cell migration	IDA	25147342
GO:0045019	Process	Negative regulation of nitric oxide biosynthetic process	IDA	11591728, 19278978
GO:0045121	Component	Membrane raft	IC	23549614
GO:0046872	Function	Metal ion binding	IEA
GO:0048306	Function	Calcium-dependent protein binding	IPI	23549614
GO:0050998	Function	Nitric-oxide synthase binding	IPI	11591728, 23549614
GO:0051001	Process	Negative regulation of nitric-oxide synthase activity	IDA	11591728, 17242280, 19278978, 19287093
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0051599	Process	Response to hydrostatic pressure	IMP	19287093
GO:0070588	Process	Calcium ion transmembrane transport	IMP	8530416
GO:0070885	Process	Negative regulation of calcineurin-NFAT signaling cascade	IDA	19287093, 25147342
GO:0070885	Process	Negative regulation of calcineurin-NFAT signaling cascade	IMP	15955804
GO:0071872	Process	Cellular response to epinephrine stimulus	IDA	19278978
GO:0097110	Function	Scaffold protein binding	ISS
GO:0097228	Component	Sperm principal piece	IEA
GO:0097553	Process	Calcium ion transmembrane import into cytosol	IC	8530416
GO:0098703	Process	Calcium ion import across plasma membrane	IC	8530416
GO:0098736	Process	Negative regulation of the force of heart contraction	IDA	17242280
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099059	Component	Integral component of presynaptic active zone membrane	IEA
GO:0140199	Process	Negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process	IDA	17242280
GO:0150104	Process	Transport across blood-brain barrier	NAS	30280653
GO:1900082	Process	Negative regulation of arginine catabolic process	IDA	19278978
GO:1901660	Process	Calcium ion export	IDA	25798335
GO:1902083	Process	Negative regulation of peptidyl-cysteine S-nitrosylation	NAS	18591664
GO:1902305	Process	Regulation of sodium ion transmembrane transport	IC	18591664
GO:1902548	Process	Negative regulation of cellular response to vascular endothelial growth factor stimulus	IDA	25147342
GO:1902806	Process	Regulation of cell cycle G1/S phase transition	IMP	24448801
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	IDA	15955804
GO:1903243	Process	Negative regulation of cardiac muscle hypertrophy in response to stress	IMP	19287093
GO:1903249	Process	Negative regulation of citrulline biosynthetic process	IDA	19278978
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1905145	Process	Cellular response to acetylcholine	ISS
GO:2000481	Process	Positive regulation of cAMP-dependent protein kinase activity	IDA	19278978

Other IDs

• MIM: 108732
• HGNC: 817
• e!Ensembl: ENSG00000058668

Protein

• UniProt ID: P23634
• Protein name: Plasma membrane calcium-transporting ATPase 4 (PMCA4) (EC 7.2.2.10) (Matrix-remodeling-associated protein 1) (Plasma membrane calcium ATPase isoform 4) (Plasma membrane calcium pump isoform 4)
• Protein function: Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell (PubMed:8530416). By regulating sperm cell calcium homeostasis, may play a role in sperm motility (By similarity).
• PDB: 1CFF, 2KNE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00690	Cation_ATPase_N	46 → 116	Cation transporter/ATPase, N-terminus	Domain
  PF00122	E1-E2_ATPase	185 → 301		Family
  PF00122	E1-E2_ATPase	335 → 443		Family
  PF13246	Cation_ATPase	508 → 604		Family
  PF00702	Hydrolase	633 → 797		Domain
  PF00689	Cation_ATPase_C	867 → 1049	Cation transporting ATPase, C-terminus	Family
  PF12424	ATP_Ca_trans_C	1089 → 1125	Plasma membrane calcium transporter ATPase C terminal	Family
  PF12424	ATP_Ca_trans_C	1126 → 1171	Plasma membrane calcium transporter ATPase C terminal	Family

• Sequence:

  MTNPSDRVLPANSMAESREGDFGCTVMELRKLMELRSRDALTQINVHYGGVQNLCSRLKT
  SPVEGLSGNPADLEKRRQVFGHNVIPPKKPKTFLELVWEALQDVTLIILEIAAIISLVLS
  FYRPAGEENELCGQVATTPEDENEAQAGWIEGAAILFSVIIVVLVTAFNDWSKEKQFRGL
  QCRIEQEQKFSIIRNGQLIQLPVAEIVVGDIAQVKYGDLLPADGILIQGNDLKIDESSLT
  GESDHVKKSLDKDPMLLSGTHVMEGSGRMVVTAVGVNSQTGIILTLLGVNEDDEGEKKKK
  GKKQGVPENRNKAKTQDGVALEIQPLNSQEGIDNEEKDKKAVKVPKKEKSVLQGKLTRLA
  VQIGKAGLLMSALTVFILILYFVIDNFVINRRPWLPECTPIYIQYFVKFFIIGITVLVVA
  VPEGLPLAVTISLAYSVKKMMKDNNLVRHLDACETMGNATAICSDKTGTLTMNRMTVVQA
  YIGGIHYRQIPSPDVFLPKVLDLIVNGISINSAYTSKILPPEKEGGLPRQVGNKTECALL
  GFVTDLKQDYQAVRNEVPEEKLYKVYTFNSVRKSMSTVIRNPNGGFRMYSKGASEIILRK
  CNRILDRKGEAVPFKNKDRDDMVRTVIEPMACDGLRTICIAYRDFDDTEPSWDNENEILT
  ELTCIAVVGIEDPVRPEVPDAIAKCKQAGITVRMVTGDNINTARAIATKCGILTPGDDFL
  CLEGKEFNRLIRNEKGEVEQEKLDKIWPKLRVLARSSPTDKHTLVKGIIDSTVGEHRQVV
  AVTGDGTNDGPALKKADVGFAMGIAGTDVAKEASDIILTDDNFTSIVKAVMWGRNVYDSI
  SKFLQFQLTVNVVAVIVAFTGACITQDSPLKAVQMLWVNLIMDTFASLALATEPPTESLL
  KRRPYGRNKPLISRTMMKNILGHAFYQLIVIFILVFAGEKFFDIDSGRKAPLHSPPSQHY
  TIVFNTFVLMQLFNEINSRKIHGEKNVFSGIYRNIIFCSVVLGTFICQIFIVEFGGKPFS
  CTSLSLSQWLWCLFIGIGELLWGQFISAIPTRSLKFLKEAGHGTTKEEITKDAEGLDEID
  HAEMELRRGQILWFRGLNRIQTQIDVINTFQTGASFKGVLRRQNMGQHLDVKLVPSSSYI
  KVVKAFHSSLHESIQKPYNQKSIHSFMTHPEFAIEEELPRTPLLDEEEEENPDKASKFGT
  RVLLLDGEVTPYANTNNNAVDCNQVQLPQSDSSLQSLETSV

• Sequence length: 1241