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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

ATP2A2 Gene

protein-coding   GIFtS: 71
GCID: GC12P110719

ATPase, Ca++ Transporting, Cardiac Muscle, Slow Twitch 2


(Previous symbols: ATP2B, DAR)
Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
ATPase, Ca++ Transporting, Cardiac Muscle, Slow Twitch 21 2     SERCA22 3
ATP2B1 2 3 5     SR Ca(2+)-ATPase 22 3
Calcium Pump 21 2 3     EC 3.6.3.83 8
DAR1 2 5     DD2
Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 21 2     ATPase, Ca++ Dependent, Slow-Twitch, Cardiac Muscle-22
Calcium-Transporting ATPase Sarcoplasmic Reticulum Type, Slow Twitch
Skeletal Muscle Isoform2 3
     Cardiac Ca2+ ATPase2
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 Gene:
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)

GeneCards Summary for ATP2A2 Gene: 
ATP2A2 (ATPase, Ca++ transporting, cardiac muscle, slow twitch 2) is a protein-coding gene. Diseases associated with ATP2A2 include acrokeratosis verruciformis, and mongolian spot, and among its related super-pathways are Hypertrophic cardiomyopathy (HCM) and Parkinson's disease. GO annotations related to this gene include S100 protein binding and protein C-terminus binding. An important paralog of this gene is ATP2C1.

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 Gene:
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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000012.11  NT_009775.17  NC_018923.2  
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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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 Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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

Explore proteomics data for ATP2A2 at MOPED 

Post-translational modifications:

  • UniProtKB: Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity
  • View modification sites using PhosphoSitePlus
  • 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 MOPED1, PaxDb2 and MAXQB3 :    About this image 

    ATP2A2 Protein Expression
    REFSEQ proteins (2 alternative transcripts): 
    NP_001672.1  NP_733765.1  

    ENSEMBL proteins: 
     ENSP00000447406   ENSP00000311186   ENSP00000366913   ENSP00000440045   ENSP00000449454  
     ENSP00000450407   ENSP00000378872  
    Reactome Protein details: P16615
    Human Recombinant Protein Products for ATP2A2: 
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    Cloud-Clone Corp. Proteins for ATP2A2 

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005789endoplasmic reticulum membrane TAS--
    GO:0005887integral to plasma membrane TAS2844796
    GO:0016020membrane IDA--
    GO:0016021integral to membrane ----
    GO:0016529sarcoplasmic reticulum IDA12804600

    ATP2A2 for ontologies           About GeneDecksing



    ATP2A2 Antibody Products: 
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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    PATP: ATPases / P-type

    IUPHAR Guide to PHARMACOLOGY protein family classification: SERCA2 
    Ca2+-ATPases

    5/9 InterPro protein domains (see all 9):
     IPR023298 ATPase_P-typ_TM_dom
     IPR023299 ATPase_P-typ_cyto_domN
     IPR008250 ATPase_P-typ_transduc_dom_A
     IPR005782 ATPase_P-typ_Ca-transp_IIA
     IPR023214 HAD-like_dom

    Graphical View of Domain Structure for InterPro Entry P16615

    ProtoNet protein and cluster: P16615

    4 Blocks protein domains:
    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


    ATP2A2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    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, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: 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 (By similarity)

         Genatlas biochemistry entry for ATP2A2:
    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

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000166nucleotide binding ----
    GO:0005388calcium-transporting ATPase activity TAS2844796
    GO:0005515protein binding IPI17526652
    GO:0005524ATP binding IEA--
    GO:0008022protein C-terminus binding IPI14749390
         
    ATP2A2 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for ATP2A2:
     Synthetic lethal with Ras 

         15/16 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Atp2a2) (see all 16):
     behavior/neurological  cardiovascular system  cellular  digestive/alimentary  growth/size 
     hematopoietic system  homeostasis/metabolism  immune system  integument  mortality/aging 
     muscle  renal/urinary system  reproductive system  respiratory system  skeleton 

    ATP2A2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for ATP2A2: Atp2a2tm1Fwuy Atp2a2tm1Ges

       inGenious Targeting Laboratory - Custom generated mouse model solutions for ATP2A2 
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ATP2A2 
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    miRNA
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    miRTarBase miRNAs that target ATP2A2:
    hsa-mir-30a (MIRT005137)

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    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 plasmidATP2A2 3' UTR sequence
    Inhib. RNA
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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for ATP2A2 About   (see all 25)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Hypertrophic cardiomyopathy (HCM)
    Hypertrophic cardiomyopathy (HCM)0.75
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Dilated cardiomyopathy0.75
    Arrhythmogenic right ventricular cardiomyopathy0.53
    2Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
    Alzheimer's disease0.46
    Alzheimers Disease0.44
    3Platelet calcium homeostasis
    Platelet calcium homeostasis0.53
    Reduction of cytosolic Ca++ levels0.53
    4Calcium Regulation in the Cardiac Cell
    Calcium Regulation in the Cardiac Cell0.43
    Myometrial Relaxation and Contraction Pathways0.43
    5Ion channel transport
    Ion channel transport0.49
    Ion transport by P-type ATPases0.32

    Pathways by source                                                                                                                                                                 See SuperPaths
    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)
        Myometrial Relaxation and Contraction Pathways
    Calcium Regulation in the Cardiac Cell
    Alzheimers Disease
    Arrhythmogenic right ventricular cardiomyopathy
    Endothelin

    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 CentralTM Interacting Genes and Proteins Network for ATP2A2

    5/54 Interacting proteins for ATP2A2 (P166152, 3) via UniProtKB, MINT, STRING, and/or I2D (see all 54)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    OPRD1P411432, 3MINT-7889342 MINT-7889483 MINT-7889371 I2D: score=1 
    TNFRSF1AP194382, 3MINT-49362 I2D: score=2 
    TNFRSF1BP203332, 3MINT-49456 I2D: score=2 
    TRADDQ156282, 3MINT-49496 I2D: score=2 
    TRAF6Q9Y4K32, 3MINT-49609 I2D: score=2 
    About this table

    Gene Ontology (GO): 5/16 biological process terms (GO ID links to tree view) (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002026regulation of the force of heart contraction IEA--
    GO:0006810transport TAS2844796
    GO:0006812cation transport ----
    GO:0006816calcium ion transport ----
    GO:0006874cellular 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, Ligands according to IUPHAR, 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
    CompoundAction CAS #
    ArtemisininAntimalarial; inhibits P-type ATPase (PfATP6) of P.falciparum[63968-64-9]
    BHQInhibitor of SERCA ATPase[88-58-4]
    Ochratoxin AStimulates SERCA-ATP-dependent Ca2+ pump activity[303-47-9]
    Cyclopiazonic acidInhibitor of SERCA ATPase[18172-33-3]
    ThapsigarginPotent inhibitor of SERCA ATPase[67526-95-8]

    2 HMDB Compounds for ATP2A2    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--
    MagnesiumMagnesium (see all 2)7439-95-4--

    10/13 Novoseek inferred 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 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, 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)
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA 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):

    AA376897 F03943 AK095382 BG370203 BM975793 F25663 CD516017 BQ002535 
    AL117505 AA121434 BM856829 BQ691462 BM983152 BF926806 BM680123 BQ016651 
    BQ631924 BE740334 CA976191 H08318 M23115 BU624756 CO249893 AA644348 

    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)      ATP2A2 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GTTTCAGGTA
    ATP2A2 Expression
    About this image


    ATP2A2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/5 selected tissues (see all 5) fully expand
     
     Brain (Nervous System)    fully expand to see all 15 entries
             Thalamus
             Septum   
     
     Spinal Cord (Nervous System)    fully expand to see all 2 entries
             Dorsal Horn   
     
     Heart (Cardiovascular System)
             Cardiomyocytes Outer Curvature
     
     Eye (Sensory Organs)
             Glycinergic Amacrine Cells Inner Nuclear Layer
     
     Skeletal Muscle (Muscoskeletal System)

    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 10/19 species (see all 19)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Atp2a21 , 5 ATPase, Ca++ transporting, cardiac muscle, slow twitch more1, 5 90.34(n)1
    98.85(a)1
      5 (62.38 cM)5
    119381  NM_001110140.31  NP_001103610.11 
     1224535135 
    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
    Uncharacterized protein
    93(a)
    1 ↔ 1
    LGb(2169271-2203709)
    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
    catp-26
    (see all 5)
    Protein CATP-2
    (see all 5)
    67(a)
    23(a)
    (see all 5)
    1 ↔ many
    possible ortholog
    (see all 5)
    III(10811906-10816845)
    V(4934706-4939085)
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes PMR16
    High affinity Ca2+/Mn2+ P-type ATPase required for...
    30(a)
    1 → many
    VII(187616-190468)
    soybean
    (Glycine max)
    eudicotyledons 444826162   -- 70.25(n)  
    barley
    (Hordeum vulgare)
    Liliopsida AJ310845.12   -- 73.65(n)    AJ310845.1 


    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  ATP2C22  ATP2A12  
    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, 4UniProtKB, 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

    10/1551 SNPs in ATP2A2 are shown (see all 1551)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0086274
    Darier disease (DD)4--see VAR_0086272 A D mis40--------
    VAR_0086264
    Darier disease (DD)4--see VAR_0086262 D N mis40--------
    VAR_0086244
    Darier disease (DD)4--see VAR_0086242 F S mis40--------
    VAR_0086174
    Darier disease (DD)4--see VAR_0086172 C F mis40--------
    VAR_0086224
    Darier disease (DD)4--see VAR_0086222 S F mis40--------
    VAR_0086234
    Darier disease (DD)4--see VAR_0086232 C R mis40--------
    VAR_0175324
    Acrokeratosis verruciformis (AKV)4--see VAR_0175322 P L mis40--------
    VAR_0095084
    Darier disease (DD)4--see VAR_0095082 T K mis40--------
    VAR_0086124
    Darier disease (DD)4--see VAR_0086122 R Q mis40--------
    VAR_0086294
    Darier disease (DD)4--see VAR_0086292 S L mis40--------

    HapMap Linkage Disequilibrium report for ATP2A2 (110718561 - 110788898 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for ATP2A2:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv28186CNV Loss19812545


    Human Gene Mutation Database (HGMD): ATP2A2
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 108740   
    OMIM disorders: 124200  101900  
    UniProtKB/Swiss-Prot: AT2A2_HUMAN, P16615
  • Acrokeratosis verruciformis (AKV) [MIM:101900]: 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. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Darier disease (DD) [MIM:124200]: A skin disorder characterized by warty papules and plaques in
    seborrheic areas (central trunk, flexures, scalp and forehead), palmoplantar pits and distinctive nail
    abnormalities. It is due to 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. Some patients
    present with hemorrhage into acantholytic vesicles on the palms and dorsal aspects of the fingers which gives
    rise to black macules. In a few families affected by Darier disease, 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. Clinical variants of Darier disease include
    hypertrophic, vesicobullous, hypopigmented, cornifying, zosteriform or linear, acute and comedonal subtypes.
    Comedonal Darier disease is characterized by the coexistence of acne-like comedonal lesions with typical Darier
    hyperkeratotic papules on light-exposed areas. At histopathologic level, comedonal Darier disease differs from
    classic Darier disease in the prominent follicular involvement and the presence of greatly elongated dermal
    villi. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 20/43 diseases for ATP2A2 (see all 43):    About MalaCards
    acrokeratosis verruciformis    mongolian spot    mitral valve stenosis    keratosis
    epidermolysis bullosa simplex with mottled pigmentation    hailey-hailey disease    epidermolysis bullosa simplex    myotonic dystrophy type 1
    achalasia    hypertension    aniridia    epidermolysis bullosa
    myotonic dystrophy    bipolar disorder    congenital heart defect    cataract
    ischemic heart disease    scoliosis    acne    hypertrophic cardiomyopathy

    4 diseases from the University of Copenhagen DISEASES database for ATP2A2:
    Keratosis follicularis     Acrokeratosis verruciformis     Hailey-Hailey disease     Heart disease

    ATP2A2 for disorders           About GeneDecksing

    10/19 Novoseek inferred 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 314):
    (articles sorted by number of sources associating them with ATP2A2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. 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)
    2. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. (PubMed id 10080178)1, 2, 3, 9 Sakuntabhai A.... Hovnanian A. (1999)
    3. A724A polymorphism of sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) in hypertensive patients. (PubMed id 17439322)1, 4, 9 Kiec-Wilk B....Kawecka-Jaszcz K. (2007)
    4. Alterations in the ATP2A2 gene in correlation with colon and lung cancer. (PubMed id 17116488)1, 4, 9 Korosec B....Ravnik-Glavac M. (2006)
    5. 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)
    6. 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)
    7. Spectrum of novel ATP2A2 mutations in patients with Darier's disease. (PubMed id 10441323)1, 2, 9 Sakuntabhai A.... Hovnanian A. (1999)
    8. 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)
    9. 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)
    10. 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)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    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
    NameDescription
    PharmGKB entry for ATP2A2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ATP2A2 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATP2A2

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for ATP2A2 gene:
    Search GeneIP for patents involving ATP2A2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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