ATP2B3 (ATPase plasma membrane Ca2+ transporting 3)

Gene

• Entrez ID: 492
• Gene name: ATPase plasma membrane Ca2+ transporting 3
• Gene symbol: ATP2B3
• Synonyms: CFAP39, CLA2, OPCA, PMCA3, PMCA3a, SCAX1
• Chromosome: X
• Chromosome location: Xq28
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs150989590	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, non coding transcript variant, coding sequence variant
rs368215361	C>G,T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs397514619	G>A	Likely-pathogenic, pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs724160009	GCTGGT>-	Pathogenic	Non coding transcript variant, inframe deletion, coding sequence variant
rs724160011	CTGGTC>-	Pathogenic	Non coding transcript variant, inframe deletion, coding sequence variant
rs724160012	TCGTGG>-	Pathogenic	Non coding transcript variant, inframe deletion, coding sequence variant
rs782596945	G>A,T	Pathogenic	Synonymous variant, genic downstream transcript variant, missense variant, 3 prime UTR variant, coding sequence variant, non coding transcript variant
rs1603040061	C>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT645896	hsa-miR-5193	HITS-CLIP	23824327
MIRT645897	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT645895	hsa-miR-877-3p	HITS-CLIP	23824327
MIRT645894	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT645893	hsa-miR-3909	HITS-CLIP	23824327
MIRT645892	hsa-miR-6852-3p	HITS-CLIP	23824327
MIRT645891	hsa-miR-4691-5p	HITS-CLIP	23824327
MIRT645889	hsa-miR-6792-3p	HITS-CLIP	23824327
MIRT645890	hsa-miR-6749-3p	HITS-CLIP	23824327
MIRT645888	hsa-miR-6881-3p	HITS-CLIP	23824327
MIRT645887	hsa-miR-676-3p	HITS-CLIP	23824327
MIRT645886	hsa-miR-670-3p	HITS-CLIP	23824327
MIRT645885	hsa-miR-1238-3p	HITS-CLIP	23824327
MIRT645884	hsa-miR-2355-3p	HITS-CLIP	23824327
MIRT645896	hsa-miR-5193	HITS-CLIP	23824327
MIRT645897	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT645895	hsa-miR-877-3p	HITS-CLIP	23824327
MIRT645894	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT645893	hsa-miR-3909	HITS-CLIP	23824327
MIRT645892	hsa-miR-6852-3p	HITS-CLIP	23824327
MIRT645891	hsa-miR-4691-5p	HITS-CLIP	23824327
MIRT645889	hsa-miR-6792-3p	HITS-CLIP	23824327
MIRT645890	hsa-miR-6749-3p	HITS-CLIP	23824327
MIRT645888	hsa-miR-6881-3p	HITS-CLIP	23824327
MIRT645887	hsa-miR-676-3p	HITS-CLIP	23824327
MIRT645886	hsa-miR-670-3p	HITS-CLIP	23824327
MIRT645885	hsa-miR-1238-3p	HITS-CLIP	23824327
MIRT645884	hsa-miR-2355-3p	HITS-CLIP	23824327
MIRT807664	hsa-miR-3144-3p	CLIP-seq
MIRT807665	hsa-miR-3187-3p	CLIP-seq
MIRT807666	hsa-miR-4435	CLIP-seq
MIRT807667	hsa-miR-455-5p	CLIP-seq
MIRT807668	hsa-miR-4643	CLIP-seq
MIRT807669	hsa-miR-4701-5p	CLIP-seq
MIRT807670	hsa-miR-4733-3p	CLIP-seq
MIRT807671	hsa-miR-548s	CLIP-seq
MIRT807672	hsa-miR-588	CLIP-seq
MIRT807673	hsa-miR-764	CLIP-seq
MIRT807674	hsa-miR-875-5p	CLIP-seq
MIRT807675	hsa-miR-296-5p	CLIP-seq
MIRT807676	hsa-miR-3918	CLIP-seq
MIRT2177846	hsa-miR-105	CLIP-seq
MIRT2177847	hsa-miR-1266	CLIP-seq
MIRT2177848	hsa-miR-3667-3p	CLIP-seq
MIRT2177849	hsa-miR-3682-5p	CLIP-seq
MIRT2177850	hsa-miR-4279	CLIP-seq
MIRT2177851	hsa-miR-4518	CLIP-seq
MIRT807667	hsa-miR-455-5p	CLIP-seq
MIRT2177852	hsa-miR-4659a-3p	CLIP-seq
MIRT2177853	hsa-miR-4659b-3p	CLIP-seq
MIRT2177854	hsa-miR-4778-3p	CLIP-seq
MIRT2177855	hsa-miR-767-3p	CLIP-seq
MIRT2177856	hsa-miR-942	CLIP-seq
MIRT2384618	hsa-miR-3121-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IBA	21873635
GO:0005515	Function	Protein binding	IPI	18029012
GO:0005516	Function	Calmodulin binding	IEA
GO:0005524	Function	ATP binding	IEA
GO:0005886	Component	Plasma membrane	IDA	18029012
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0015085	Function	Calcium ion transmembrane transporter activity	IDA	18029012
GO:0019829	Function	ATPase-coupled cation transmembrane transporter activity	IBA	21873635
GO:0030165	Function	PDZ domain binding	IBA	21873635
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0046872	Function	Metal ion binding	IEA
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IDA	18029012
GO:0098793	Component	Presynapse	IEA
GO:0098978	Component	Glutamatergic synapse	IDA	18029012
GO:0098978	Component	Glutamatergic synapse	IMP	18029012
GO:0098982	Component	GABA-ergic synapse	IDA	18029012
GO:0098982	Component	GABA-ergic synapse	IMP	18029012
GO:0099509	Process	Regulation of presynaptic cytosolic calcium ion concentration	IEA
GO:1903561	Component	Extracellular vesicle	HDA	24769233
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1905056	Function	Calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration	IDA	18029012
GO:1905056	Function	Calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration	IMP	18029012
GO:1990034	Process	Calcium ion export across plasma membrane	IDA	18029012

Other IDs

• MIM: 300014
• HGNC: 816
• e!Ensembl: ENSG00000067842

Protein

• UniProt ID: Q16720
• Protein name: Plasma membrane calcium-transporting ATPase 3 (PMCA3) (EC 7.2.2.10) (Plasma membrane calcium ATPase isoform 3) (Plasma membrane calcium pump isoform 3)
• Protein function: ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels at the presynaptic terminals (PubMed:18029012, PubMed:22912398, PubMed:25953895, PubMed:27035656). Uses ATP as an energy source to transport cytosolic Ca
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00690	Cation_ATPase_N	51 → 121	Cation transporter/ATPase, N-terminus	Domain
  PF00122	E1-E2_ATPase	190 → 306		Family
  PF00122	E1-E2_ATPase	341 → 451		Family
  PF13246	Cation_ATPase	516 → 612		Family
  PF00689	Cation_ATPase_C	876 → 1058	Cation transporting ATPase, C-terminus	Family
  PF12424	ATP_Ca_trans_C	1100 → 1146	Plasma membrane calcium transporter ATPase C terminal	Family

• Sequence:

  MGDMANSSIEFHPKPQQQRDVPQAGGFGCTLAELRTLMELRGAEALQKIEEAYGDVSGLC
  RRLKTSPTEGLADNTNDLEKRRQIYGQNFIPPKQPKTFLQLVWEALQDVTLIILEVAAIV
  SLGLSFYAPPGEESEACGNVSGGAEDEGEAEAGWIEGAAILLSVICVVLVTAFNDWSKEK
  QFRGLQSRIEQEQKFTVIRNGQLLQVPVAALVVGDIAQVKYGDLLPADGVLIQANDLKID
  ESSLTGESDHVRKSADKDPMLLSGTHVMEGSGRMVVTAVGVNSQTGIIFTLLGAGGEEEE
  KKDKKGKQQDGAMESSQTKAKKQDGAVAMEMQPLKSAEGGEMEEREKKKANAPKKEKSVL
  QGKLTKLAVQIGKAGLVMSAITVIILVLYFVIETFVVEGRTWLAECTPVYVQYFVKFFII
  GVTVLVVAVPEGLPLAVTISLAYSVKKMMKDNNLVRHLDACETMGNATAICSDKTGTLTT
  NRMTVVQSYLGDTHYKEIPAPSALTPKILDLLVHAISINSAYTTKILPPEKEGALPRQVG
  NKTECALLGFVLDLKRDFQPVREQIPEDKLYKVYTFNSVRKSMSTVIRMPDGGFRLFSKG
  ASEILLKKCTNILNSNGELRGFRPRDRDDMVRKIIEPMACDGLRTICIAYRDFSAGQEPD
  WDNENEVVGDLTCIAVVGIEDPVRPEVPEAIRKCQRAGITVRMVTGDNINTARAIAAKCG
  IIQPGEDFLCLEGKEFNRRIRNEKGEIEQERLDKVWPKLRVLARSSPTDKHTLVKGIIDS
  TTGEQRQVVAVTGDGTNDGPALKKADVGFAMGIAGTDVAKEASDIILTDDNFTSIVKAVM
  WGRNVYDSISKFLQFQLTVNVVAVIVAFTGACITQDSPLKAVQMLWVNLIMDTFASLALA
  TEPPTESLLLRKPYGRDKPLISRTMMKNILGHAVYQLAIIFTLLFVGELFFDIDSGRNAP
  LHSPPSEHYTIIFNTFVMMQLFNEINARKIHGERNVFDGIFSNPIFCTIVLGTFGIQIVI
  VQFGGKPFSCSPLSTEQWLWCLFVGVGELVWGQVIATIPTSQLKCLKEAGHGPGKDEMTD
  EELAEGEEEIDHAERELRRGQILWFRGLNRIQTQIRVVKAFRSSLYEGLEKPESKTSIHN
  FMATPEFLINDYTHNIPLIDDTDVDENEERLRAPPPPSPNQNNNAIDSGIYLTTHVTKSA
  TSSVFSSSPGSPLHSVETSL

• Sequence length: 1220

Pathways

KEGG:

Calcium signaling pathway
cGMP-PKG signaling pathway
cAMP signaling pathway
Adrenergic signaling in cardiomyocytes
Aldosterone synthesis and secretion
Endocrine and other factor-regulated calcium reabsorption
Salivary secretion
Pancreatic secretion
Mineral absorption

Reactome:

Reduction of cytosolic Ca++ levels
Ion homeostasis
Ion transport by P-type ATPases

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Hyperaldosteronism	NON RARE IN EUROPE: Aldosterone-producing adenoma, Hyperaldosteronism	rs28934586, rs104894068, rs387906778, rs386352319, rs587777437, rs587777438, rs587777439, rs786205050, rs771507094, rs1085307938, rs1553853557, rs1553856214, rs1293789661, rs1553857113, rs758379595	23416519
Aldosterone-producing adrenal cortex adenoma	Aldosterone-Producing Adrenal Cortex Adenoma	rs724160008, rs11540945, rs724160010, rs724160009, rs724160011, rs724160012
Cerebellar ataxia, x-linked	X-linked non progressive cerebellar ataxia	rs397514619, rs782596945
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Hypertension	Hypertensive disease	rs13306026, rs13333226	23416519
Hypotonia	Neonatal Hypotonia	rs141138948, rs397517172, rs869312824, rs1583169151
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896
Spinocerebellar ataxia, x-linked	SPINOCEREBELLAR ATAXIA, X-LINKED 1	rs797044558	22912398

Unknown
Disease name	Disease term	dbSNP ID	References
Adenoma	Adenoma, Adenoma, Basal Cell, Follicular adenoma, Adenoma, Microcystic, Adenoma, Monomorphic, Adenoma, Trabecular		23416519
Cerebellar atrophy	Cerebellar atrophy
Cerebellar hypoplasia	Cerebellar Hypoplasia
Conn syndrome	Conn Syndrome		23416519
Dysarthria	Dysarthria
Motor delay	Clumsiness - motor delay
Oropharyngeal dysphagia	Oropharyngeal Dysphagia
Papillary adenoma	Papillary adenoma		23416519
Strabismus	Strabismus