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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

ATP2A2 Gene

protein-coding GIFtS: 70
GCID: GC12P110719

ATPase, Ca++ transporting, cardiac muscle, slow twitch 2

(Previous symbols: ATP2B, DAR)

Explore 50 diseases affiliated with
ATP2A2 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
ATPase, Ca++ Transporting, Cardiac Muscle, Slow Twitch 2¹ ²		SR Ca(2+)-ATPase 2² ³
ATP2B¹ ² ³ ⁵		EC 3.6.3.8³ ⁸
SERCA2¹ ² ³		DD²
DAR¹ ² ⁵		ATPase, Ca++ Dependent, Slow-Twitch, Cardiac Muscle-2²
Calcium Pump 2² ³		Cardiac Ca2+ ATPase²
Calcium-Transporting ATPase Sarcoplasmic Reticulum Type, Slow Twitch Skeletal Muscle Isoform² ³		Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2²
Endoplasmic Reticulum Class 1/2 Ca(2+) ATPase² ³		EC 3.6.3⁸

External Ids:	HGNC: 812¹	Entrez Gene: 488²	Ensembl: ENSG00000174437⁷	OMIM: 108740⁵	UniProtKB: P16615³

Export aliases for ATP2A2 gene to outside databases

Previous GC identifers: GC12P109794 GC12P110566 GC12P109182 GC12P107737

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for ATP2A2:

This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or

endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of

calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the

contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis,

an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal

keratinization. Alternative splicing results in multiple transcript variants encoding different isoforms. (provided by

RefSeq, Oct 2008)

UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615

Function: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium

from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the

contraction/relaxation cycle

summary for ATP2A2:

Ca2+-ATPases function to maintain a low cytoplasmic conentration of Ca2+ ions. They are high affinity, low

capacitance transporters and compliment the actions of the low affinity, high capacitance Na+/Ca2+

exchanger. Ca2+-ATPases are P-type ATPases and there are two varients; a plasma membrane-bound Ca2+-ATPase

(PMCA) and a sacroplasmic reticulum Ca2+-ATPase (SERCA). PMCA exists as a dimer within the plasma membrane

of a wide variety of cell types and, using the energy released from ATP hydrolysis, transports Ca2+ ions out

of the cell against the concentration gradient. SERCA is located in the sarcoplasmic reticulum (SR) of

muscle cells and transports Ca2+ ions from the cytoplasm into the SR lumen during muscle relaxation. PMCA

transports one Ca2+ ion per ATP molecule hydrolyzed, whilst SERCA can transport two. PMCAs are regulated by

calmodulin and the phospholipid composition of the surrounding plasma membrane. Furthermore, PMCA can be

phosphorylated by PKA, PKC, Src and FAK at specific residues to influence activity. So far, only one human

pathology has been linked to PMCA defects; deafness. However, SERCA defects have been implicated in a wide

array of pathologies including heart failure, sperm motility defects, cataract formation, carcinogenesis,

diabetes, and cardiac hypertension and hypertrophy.

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_009775.17

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the ATP2A2 gene promoter:
Sp1 STAT3
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ATP2A2 promoter sequence

Search SABiosciences Chromatin IP Primers for ATP2A2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ATP2A2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q24.11 Ensembl cytogenetic band: 12q24.11 HGNC cytogenetic band: 12q24.11

ATP2A2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ATP2A2 gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12P110719: view genomic region (about GC identifiers)

Start:	110,718,561 bp from pter	End:	110,788,898 bp from pter
Size:	70,338 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615 (See protein sequence)

Recommended Name: Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Size: 1042 amino acids; 114757 Da

Subunit: Associated with phospholamban (PLN) (By similarity). Isoform 1 interacts with TRAM2 (via C-terminus).

Interacts with HAX1. Interacts with S100A8 and S100A9 (By similarity)

Subcellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein. Sarcoplasmic reticulum membrane;

Multi-pass membrane protein

Sequence caution: Sequence=BAG57266.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

Secondary accessions: A6NDN7 B4DF05 P16614 Q86VJ2

Alternative splicing: 5 isoforms: P16615-1 P16615-2 P16615-3 P16615-4 P16615-5 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ATP2A2: NX_P16615

Post-translational modifications:

Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P16615

4/69 DME Specific Peptides for ATP2A2 (P16615) (see all 69)

VPGDIVE

AICRRIG

TGSTYAP

HKSKIVE

ATP2A2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001672.1 NP_733765.1

ENSEMBL proteins:

ENSP00000447406 ENSP00000311186 ENSP00000366913 ENSP00000440045 ENSP00000449454

ENSP00000448296 ENSP00000450407 ENSP00000378872

Reactome Protein details: P16615
Human Recombinant Protein Products:

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	Browse recombinant and purified proteins available from Enzo Life Sciences
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	Novus Biologicals ATP2A2 Protein Novus Biologicals ATP2A2 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for ATP2A2

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005624	membrane fraction	--	--
GO:0005789	endoplasmic reticulum membrane	TAS	--
GO:0005792	microsome	--	--
GO:0005887	integral to plasma membrane	TAS	2844796
GO:0016020	membrane	TAS	2844796

ATP2A2 for ontologies About GeneDecksing

ATP2A2 Antibody Products:

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	Cell Signaling Technology (CST) Antibodies for ATP2A2 (SERCA2)
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	GenScript Custom Superior Antibodies Services for ATP2A2
	Novus Biologicals ATP2A2 Antibodies
	Abcam antibodies for ATP2A2
	Uscn Antibodies for ATP2A2
	ThermoFisher Antibody for ATP2A2

Assay Products for ATP2A2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
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	GenScript Custom Assay Services for ATP2A2
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for ATP2A2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

ATP2A2 for domains About GeneDecksing

5/10 InterPro domains/families (see all 10):

IPR023298 ATPase_P-typ_TM_dom

IPR023306 ATPase_cation_domN

IPR023299 ATPase_P-typ_cyto_domN

IPR008250 ATPase_P-typ_transduc_dom_A

IPR005782 ATPase_P-typ_Ca-transp

Graphical View of Domain Structure for InterPro Entry P16615

ProtoNet protein and cluster: P16615

4 Blocks protein families:

IPB000695 H+-transporting ATPase (proton pump) signature

IPB001757 ATPase

IPB006068 Cation transporting ATPase

IPB008250 E1-E2 ATPase-associated region

UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615

Similarity: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615

Function: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium

from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the

contraction/relaxation cycle

Catalytic activity: ATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate + Ca(2+)(Side 2)

Enzyme regulation: Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. Dephosphorylated PLN

decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN

ATPase,Ca++ transporting,expressed in the sarcoplasmic reticullum of the heart (SERCA2A) rate determining factor of

Ca2+ reuptake into the SR,regulated by phospholamban,also expressed in the heart,slow-twitch muscle,highly expressed

in keratinocytes,including two isoforms,a (D12S2026),b (D12S1965). Ca2+ pump,playing a pivotal role in intracellular

Ca2+ signaling

Enzyme Numbers (IUBMB): EC 3.6.3.8¹ ² EC 3.6.3²

miRNA Products:		miRTarBase miRNAs that target ATP2A2: hsa-mir-30a (MIRT005137)

		OriGene 3'-UTR Clone (see all 3): ATP2A2 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ATP2A2
		8/117 QIAGEN miScript miRNA Assays for microRNAs that regulate ATP2A2 (see all 117):
		hsa-miR-579 hsa-miR-576-3p hsa-miR-3152-3p hsa-miR-300 hsa-miR-1258 hsa-miR-200a hsa-miR-30d hsa-miR-138-2*

		SwitchGear 3'UTR luciferase reporter plasmid: ATP2A2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for ATP2A2 (see all 7) OriGene shRNA RFP: ATP2A2 OriGene siRNA: ATP2A2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat ATP2A2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for ATP2A2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
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		GenScript: all cDNA clones in your preferred vector (see all 2): ATP2A2 (NM_170665)
		Browse Sino Biological Human cDNA Clones
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ATP2A2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for ATP2A2
		Search LifeMap BioReagents cell lines for ATP2A2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ATP2A2

Gene Ontology (GO): 5/9 molecular function terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005388	calcium-transporting ATPase activity	TAS	2844796
GO:0005509	calcium ion binding	--	--
GO:0005515	protein binding	--	--
GO:0005524	ATP binding	IEA	--
GO:0008022	protein C-terminus binding	IPI	14749390

ATP2A2 for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for ATP2A2:

Synthetic lethal with Ras

Animal Models:
Mouse knock-outs for ATP2A2: Atp2a2^tm1Fwuy Atp2a2^tm1Ges
12 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Atp2a2):

behavior/neurological	cardiovascular system	digestive/alimentary	growth/size	homeostasis/metabolism
integument	mortality/aging	muscle	renal/urinary system	reproductive system
respiratory system	tumorigenesis

ATP2A2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/26 super-pathways (see all 26) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Ion channel transport

Ion channel transport

1.00

Ion transport by P-type ATPases

0.32

Platelet calcium homeostasis

Platelet calcium homeostasis

1.00

Reduction of cytosolic Ca++ levels

0.53

Signal transduction Calcium signaling

Signal transduction Calcium signaling

1.00

Signal transduction_Calcium signaling

0.97

Calcium Regulation in the Cardiac Cell

Calcium Regulation in the Cardiac Cell

1.00

Myometrial Relaxation and Contraction Pathways

0.43

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

1.00

Arrhythmogenic right ventricular cardiomyopathy

0.99

Pathway sources
See GeneCards unified pathways
Show all pathways

2 EMD Millipore Pathways for ATP2A2

	Signal transduction Calcium signaling
	Development Beta-adrenergic receptors signaling via cAMP

4 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for ATP2A2

	Calcium Mediated T-Cell Apoptosis
	Intracellular Calcium Signaling
	Beta-Adrenergic Signaling
	Dopamine-DARPP32 Feedback onto cAMP Pathway

3 Cell Signaling Technology (CST) Pathways for ATP2A2

	Translational Control
	Ca, cAMP and Lipid Signaling
	Glucose / Energy Metabolism

2 GeneGo (Thomson Reuters) Pathways for ATP2A2

	Development Beta-adrenergic receptors signaling via cAMP
	Signal transduction Calcium signaling

5/6 BioSystems Pathways for ATP2A2 (see all 6)

	Calcium Regulation in the Cardiac Cell
	Myometrial Relaxation and Contraction Pathways
	Arrhythmogenic right ventricular cardiomyopathy
	Endothelin
	Alzheimers Disease

5/7 Reactome Pathways for ATP2A2 (see all 7)

	Hemostasis
	Transmembrane transport of small molecules
	Ion channel transport
	Platelet homeostasis
	Ion transport by P-type ATPases

3 PharmGKB Pathways for ATP2A2

	Antiarrhythmic Pathway, Pharmacodynamics
	Celecoxib Pathway, Pharmacodynamics
	Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics

5/7 Kegg Pathways (Kegg details for ATP2A2) (see all 7):

	Calcium signaling pathway
	Cardiac muscle contraction
	Pancreatic secretion
	Alzheimer's disease
	Hypertrophic cardiomyopathy (HCM)

ATP2A2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for ATP2A2

5/48 Interacting proteins for ATP2A2 (P16615^{2, 3}) via UniProtKB, MINT, STRING, and/or I2D (see all 48)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
OPRD1	P41143²^,³	MINT-7889342 MINT-7889483 MINT-7889371 I2D: score=1
TNFRSF1A	P19438²^,³	MINT-49362 I2D: score=2
TNFRSF1B	P20333²^,³	MINT-49456 I2D: score=2
TRADD	Q15628²^,³	MINT-49496 I2D: score=2
TRAF6	Q9Y4K3²^,³	MINT-49609 I2D: score=2

About this table

Gene Ontology (GO): 5/17 biological process terms (GO ID links to tree view) (see all 17): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002026	regulation of the force of heart contraction	IEA	--
GO:0006754	ATP biosynthetic process	IEA	--
GO:0006810	transport	TAS	2844796
GO:0006816	calcium ion transport	--	--
GO:0006874	cellular calcium ion homeostasis	TAS	--

ATP2A2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

ATP2A2 for compounds About GeneDecksing

EMD Millipore small molecules for ATP2A2:
Small Molecule - inhibitor

Browse drugs & compounds from Enzo Life Sciences

Compounds for ATP2A2 available from Tocris Bioscience About this table

Compound	Action	CAS #
Cyclopiazonic acid	Inhibitor of SERCA ATPase	[18172-33-3]
POM 1	Inhibitor of E-NTPDases	[12141-67-2]
BHQ	Inhibitor of SERCA ATPase	[88-58-4]
Thapsigargin	Potent inhibitor of SERCA ATPase	[67526-95-8]

2 HMDB Compounds for ATP2A2 About this table

Compound	Synonyms	CAS #	PubMed Ids
Calcium	Ca (see all 2)	7440-70-2	--
Magnesium	Magnesium (see all 2)	7439-95-4	--

10/13 Novoseek chemical compound relationships for ATP2A2 gene (see all 13) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
calcium	66.8	179	9244202 (5), 16105684 (4), 2146166 (4), 15840101 (4) (see all 75)
etomoxir	63.1	1	11866664 (1)
ryanodine	62.2	8	11489771 (2), 11576540 (1), 19458227 (1), 15792839 (1) (see all 7)
thapsigargin	52.8	3	18971376 (1), 19556421 (1)
inositol 1,4,5 trisphosphate	19.6	1	19458227 (1)
ribonucleic acid	5.41	1	15582321 (1)
nadh	0	2	10603952 (1), 9833153 (1)
oxygen	0	1	18172601 (1)
nitric oxide	0	1	17257557 (1)
glycogen	0	1	18528823 (1)

Search CenterWatch for drugs/clinical trials and news about ATP2A2 / AT2A2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for ATP2A2 gene (3 alternative transcripts):

NM_001681.3 NM_170665.3 NM_001135765.1

Unigene Cluster for ATP2A2:

ATPase, Ca++ transporting, cardiac muscle, slow twitch 2

Hs.506759 [show with all ESTs]

Unigene Representative Sequence: NM_170665

13 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000552636 ENST00000308664(uc001tql.4) ENST00000377685(uc009zvn.3)

ENST00000539276 ENST00000548169 ENST00000550248 ENST00000547050 ENST00000549840

ENST00000550262 ENST00000547792 ENST00000313432(uc001tqn.4) ENST00000553144

ENST00000395494(uc001tqk.4 uc021rdt.1)

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ATP2A2
		8/117 QIAGEN miScript miRNA Assays for microRNAs that regulate ATP2A2 (see all 117):
		hsa-miR-579 hsa-miR-576-3p hsa-miR-3152-3p hsa-miR-300 hsa-miR-1258 hsa-miR-200a hsa-miR-30d hsa-miR-138-2*

		SwitchGear 3'UTR luciferase reporter plasmid: ATP2A2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for ATP2A2 (see all 6) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for ATP2A2 (see all 3) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): ATP2A2 (NM_170665)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for ATP2A2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ATP2A2

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for ATP2A2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat ATP2A2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat ATP2A2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat ATP2A2

Additional cDNA sequence:

AK000300.1 AK095382.1 AK293877.1 AL117505.1 AY186578.1 BC035588.1 BC065753.1 BX648282.1

M23114.1 M23115.1

24/25 DOTS entries (see all 25):

DT.100038203 DT.95109821 DT.91701524 DT.80100763 DT.121180770 DT.92464965 DT.121180724 DT.100798281

DT.100798282 DT.95264928 DT.121180743 DT.92464936 DT.100798277 DT.121180727 DT.121180816 DT.40192639

DT.91662034 DT.92011905 DT.92464952 DT.95264914 DT.100726768 DT.121180689 DT.40133548 DT.91651181

24/903 AceView cDNA sequences (see all 903):

N42078 CK904992 BM720796 AA281181 BU686170 F06307 AA496781 AA644348

BU430214 CD678529 CD366948 BU147261 N30396 AL046039 C04761 CD678570

N85731 BU676849 BF194756 BQ229918 BF435070 BM145742 BM555252 BM997351

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

ATP2A2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: GTTTCAGGTA

About this image

ATP2A2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Heart

Outer Curvature

Cardiomyocytes

Selective marker (cell-identifying gene)

Myocardium

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See ATP2A2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for ATP2A2

SOURCE GeneReport for Unigene cluster: Hs.506759

UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615

Tissue specificity: Isoform 1 is widely expressed in smooth muscle and nonmuscle tissues such as in adult skin

epidermis, with highest expression in liver, pancreas and lung, and intermediate expression in brain, kidney and

placenta. Also expressed at lower levels in heart and skeletal muscle. Isoforms 2 and 3 are highly expressed in the

heart and slow twitch skeletal muscle. Expression of isoform 3 is predominantly restricted to cardiomyocytes and in

close proximity to the sarcolemma. Both isoforms are mildly expressed in lung, kidney, liver, pancreas and placenta.

Expression of isoform 3 is amplified during monocytic differentiation and also observed in the fetal heart

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for ATP2A2 gene from 8/31 species (see all 31) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	ATP2A2¹	ATPase, Ca++ transporting, cardiac muscle, slow twitch more	81.77(n) 93.95(a)		396446 XM_415130.3 XP_415130.2
lizard (Anolis carolinensis)	Reptilia	ATP2A2⁶	--	93(a)	1 ↔ 1	LGb(2174915-2203709)
tropical clawed frog (Xenopus tropicalis)	Amphibia	Str.10843²	Transcribed sequence with strong similarity to protein more	79.22(n)		BX742414.1
zebrafish (Danio rerio)	Actinopterygii	atp2a2a¹	ATPase, Ca++ transporting, cardiac muscle, slow twitch more	76.15(n) 87.84(a)		393940 NM_200965.1 NP_957259.1
fruit fly (Drosophila melanogaster)	Insecta	Ca-P60A³	calcium ion transport calcium-transporting ATPase	72(a)		60A11 --
worm (Caenorhabditis elegans)	Secernentea	sca-1⁶	SERCA (Sarco-Endoplasmic Reticulum Calcium ATPase)...	67(a)	1 → many	III(10811807-10816746)
thale cress (Arabidopsis thaliana)	eudicotyledons	ECA3⁶ ECA2⁶ (see all 4)	Ca2+-transporting ATPase (see all 4)	54(a) 48(a) (see all 4)	1 ↔ many possible ortholog (see all 4)	1(3310930-3322213) 4(382663-386529)
rice (Oryza sativa)	Liliopsida	-- -- (see all 3)	calcium-transporting ATPase 2, endoplasmic reticul... calcium-transporting ATPase, endoplasmic reticulum... (see all 3)	53(a) 47(a) (see all 3)	possible ortholog possible ortholog (see all 3)	5(1083889-1086151) 3(9631581-9641029)

ENSEMBL Gene Tree for ATP2A2 (if available)
TreeFam Gene Tree for ATP2A2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for ATP2A2 gene

ATP2C1² ATP2A3² ATP1A2² ATP2C2² ATP1A4² ATP2A1² ATP4A² ATP1A3²

ATP12A² ATP1A1²

10 SIMAP similar genes for ATP2A2 using alignment to 8 protein entries: AT2A2_HUMAN (see all proteins):

ATP2A1 DKFZp779G2251 DKFZp779O2152 ATP2A3 ATP1A4 ATP1A3

DKFZp686I0955 ATP2C2 ATP2C1 ATP1A2

ATP2A2 for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for ATP2A2
PGOHUM00000238367

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28929478^1,2	C	pathogenic	107738300(+)	`TACGGG/AGCTGA`	4	/E /G	mis¹ ese³		1		NA	2
rs3847951^1,2	C,F,	--	107735705(-)	`gtcccA/Tgctac`	2	--	us2k¹ tfbs³		1		WA	118
rs113792954^1,2		--	107736805(+)	`GCAAAG/TCATCT`	2	--	us2k¹		1		CSA	2
rs4344555^1,2	C,F,H	--	107736914(+)	`TCCTAG/TCCCAA`	2	--	us2k¹		5		EA NS NA	278
rs3026432^1,2	C	--	107737741(+)	`CTTCGC/TCGCAG`	2	--	ut5¹		0	--	--	--	--
rs3026433^1,2	C,F,	--	107737830(+)	`CCTCGC/GCGCGT`	2	--	ut5¹		1		NA	120
rs113872372^1,2		--	107738806(+)	`TTTCAC/TGCTTA`	2	--	int¹		1		CSA	2
rs111631659^1,2	C,	--	107738965(+)	`AGAAAG/AACGAA`	2	--	int¹		1		CSA	2
rs113009436^1,2	C	--	107739153(+)	`TCTTAA/C/GAGGAA`	2	--	int¹		1		CSA	1
rs55954453^1,2	C	--	107739337(+)	`ATATTC/TGGAGT`	2	--	int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for ATP2A2 (110718561 - 110788898 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for ATP2A2
1 Indel: 71577
Human Gene Mutation Database (HGMD): ATP2A2

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

ATP2A2 for disorders           About GeneDecksing

OMIM gene information: 108740
OMIM disorders: 124200  101900
UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615

Defects in ATP2A2 are a cause of acrokeratosis verruciformis (AKV) [MIM:101900]; also known as Hopf disease.

AKV is a localized disorder of keratinization, which is inherited as an autosomal dominant trait. Its onset is early

in life with multiple flat-topped, flesh-colored papules on the hands and feet, punctate keratoses on the palms and

soles, with varying degrees of nail involvement. The histopathology shows a distinctive pattern of epidermal features

with hyperkeratosis, hypergranulosis, and acanthosis together with papillomatosis. These changes are frequently

associated with circumscribed elevations of the epidermis that are said to resemble church spires. There are no

features of dyskeratosis or acantholysis, the typical findings in lesions of Darier disease

Defects in ATP2A2 are the cause of Darier disease (DD) [MIM:124200]; also known as Darier-White disease (DAR).

DD is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells

(acantholysis) and abnormal keratinization. Patients with mild disease may have no more than a few scattered keratotic

papules or subtle nail changes, whereas those with severe disease are handicapped by widespread malodorous keratotic

plaques. In a few families, neuropsychiatric abnormalities such as mild mental retardation, schizophrenia, bipolar

disorder and epilepsy have been reported. Stress, UV exposure, heat, sweat, friction, and oral contraception

exacerbate disease symptoms. Prevalence has been estimated at 1 in 50000. Clinical variants of DD include

hypertrophic, vesicobullous, hypopigmented, cornifying, zosteriform or linear, acute and comedonal subtypes. Comedonal

Darier disease (CDD) is characterized by the coexistence of acne-like comedonal lesions with typical Darier

hyperkeratotic papules on light-exposed areas. At histopathologic level, CDD differs from classic DD in the prominent

follicular involvement and the presence of greatly elongated dermal villi

20/50 diseases for ATP2A2 (see all 50): About MalaCards

hailey-hailey disease keratosis epidermolysis bullosa simplex with mottled pigmentation acrokeratosis verruciformis

epidermolysis bullosa simplex epidermolysis bullosa cataract hypertension

mitral valve stenosis myotonic dystrophy type 1 major affective disorder myotonic dystrophy

type 2 diabetes mellitus bipolar affective disorder congenital heart defect chronic obstructive pulmonary disease

ventricular fibrillation ischemic heart disease oral squamous cell carcinoma squamous cell carcinoma

4 diseases from the University of Copenhagen DISEASES database for ATP2A2:

Keratosis follicularis Acrokeratosis verruciformis Hailey-Hailey disease Heart disease

10/19 Novoseek disease relationships for ATP2A2 gene (see all 19) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
darier disease	97.5	103	12890216 (4), 12974140 (4), 11244492 (2), 12542527 (2) (see all 68)
hailey-hailey disease	84.5	6	18060195 (1), 15888147 (1), 16029335 (1), 15149492 (1) (see all 5)
acrokeratosis verruciformis	79.6	2	12542527 (2)
skin diseases	66	11	11389134 (1), 15327552 (1), 16397524 (1), 15888147 (1) (see all 9)
heart failure	58.8	14	16902596 (3), 9476544 (1), 10603952 (1), 9244202 (1) (see all 11)
affective disorder major	43.8	2	11986988 (1)
bipolar disorder	43.4	4	11244492 (2), 11986988 (1)
mood disorders	40.1	1	11986988 (1)
cardiac hypertrophy	40.1	4	9587474 (1), 16902596 (1), 8930809 (1), 10750595 (1)
hypertrophy	25.9	2	11489771 (1), 16902596 (1)

Genetic Association Database (GAD): ATP2A2
Human Genome Epidemiology (HuGE) Navigator: ATP2A2 (9 documents)

Export disorders for ATP2A2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for ATP2A2 gene, integrated from 9 sources (see all 299):
(articles sorted by number of sources associating them with ATP2A2)

Utopia: connect your pdf to the dynamic
world of online information

ATP2A2 mutations in Darier's disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. (PubMed id 10441324)^{1, 2, 4, 9} Ruiz-Perez V.L.... Strachan T. (1999)
Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. (PubMed id 10080178)^{1, 2, 3, 9} Sakuntabhai A.... Hovnanian A. (1999)
The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival. (PubMed id 18971376)^{1, 2, 9} Vafiadaki E.... Kranias E.G. (2009)
ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. (PubMed id 10441325)^{1, 2, 9} Jacobsen N.J.O.... Owen M.J. (1999)
Spectrum of novel ATP2A2 mutations in patients with Darier's disease. (PubMed id 10441323)^{1, 2, 9} Sakuntabhai A.... Hovnanian A. (1999)
Exclusion of the Darier's disease gene, ATP2A2, as a common susceptibility gene for bipolar disorder. (PubMed id 11244492)^{1, 4, 9} Jacobsen N.J....Craddock N. (2001)
Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease. (PubMed id 12542527)^{1, 2, 9} Dhitavat J.... Hovnanian A. (2003)
Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c). (PubMed id 16402920)^{1, 2, 9} Dally S....Enouf J. (2006)
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. (PubMed id 17081983)^{1, 2} Olsen J.V....Mann M. (2006)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 488	HGNC: 812	AceView: ATP2A2	Ensembl:ENSG00000174437	euGenes: HUgn488
ECgene: ATP2A2	Kegg: 488	H-InvDB: ATP2A2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for ATP2A2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for ATP2A2	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATP2A2

Intellectual Property for ATP2A2 gene
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Patent Information for ATP2A2 gene:
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GeneCards and IP:
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ATP2A2 Gene

ATPase, Ca++ transporting, cardiac muscle, slow twitch 2

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ATP2A2 Gene

ATPase, Ca++ transporting, cardiac muscle, slow twitch 2

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