Human Gene ATP2A2 (ENST00000539276.7) Description and Page Index
  Description: Homo sapiens ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2), transcript variant b, mRNA. (from RefSeq NM_170665)
RefSeq Summary (NM_170665): This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. 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. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019].
Gencode Transcript: ENST00000539276.7
Gencode Gene: ENSG00000174437.17
Transcript (Including UTRs)
   Position: hg38 chr12:110,281,247-110,351,093 Size: 69,847 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg38 chr12:110,281,790-110,346,470 Size: 64,681 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:110,281,247-110,351,093)mRNA (may differ from genome)Protein (1042 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: AT2A2_HUMAN
DESCRIPTION: RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 2; Short=SERCA2; Short=SR Ca(2+)-ATPase 2; EC=3.6.3.8; AltName: Full=Calcium pump 2; AltName: Full=Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform; AltName: Full=Endoplasmic reticulum class 1/2 Ca(2+) ATPase;
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).
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.
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.
PTM: Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity.
DISEASE: 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.
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.
SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
SEQUENCE CAUTION: Sequence=BAG57266.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATP2A2";

-  MalaCards Disease Associations
  MalaCards Gene Search: ATP2A2
Diseases sorted by gene-association score: darier disease* (1714), acrokeratosis verruciformis* (1608), hailey-hailey disease (27), bipolar disorder (17), tinea manuum (16), keratosis (14), pseudomyotonia (12), glomangiomatosis (12), lichen nitidus (11), frey syndrome (11), mitral valve stenosis (9), cardiovascular organ benign neoplasm (9), benign perivascular tumor (9), pompholyx (8), pityriasis rubra pilaris (8), yellow nail syndrome (7), brody myopathy (7), deafness, autosomal dominant 25 (6), dowling-degos disease (6), seborrheic dermatitis (5), bullous skin disease (5), catecholaminergic polymorphic ventricular tachycardia (5), subcorneal pustular dermatosis (4), dilated cardiomyopathy (4), ichthyosis bullosa of siemens (4), norwegian scabies (4), skin disease (3), heart disease (2), cardiomyopathy (2), schizophrenia (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 365.38 RPKM in Muscle - Skeletal
Total median expression: 2471.24 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -347.60543-0.640 Picture PostScript Text
3' UTR -1461.804623-0.316 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR023306 - ATPase_cation_domN
IPR008250 - ATPase_P-typ_ATPase-assoc-dom
IPR005782 - ATPase_P-typ_Ca-transp
IPR006068 - ATPase_P-typ_cation-transptr_C
IPR004014 - ATPase_P-typ_cation-transptr_N
IPR023300 - ATPase_P-typ_cyto_domA
IPR023299 - ATPase_P-typ_cyto_domN
IPR000695 - ATPase_P-typ_H-transp
IPR001757 - ATPase_P-typ_ion-transptr
IPR018303 - ATPase_P-typ_P_site
IPR023298 - ATPase_P-typ_TM_dom
IPR005834 - Dehalogen-like_hydro
IPR023214 - HAD-like_dom

Pfam Domains:
PF00689 - Cation transporting ATPase, C-terminus
PF00690 - Cation transporter/ATPase, N-terminus
PF00122 - E1-E2 ATPase
PF00702 - haloacid dehalogenase-like hydrolase

ModBase Predicted Comparative 3D Structure on P16615
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005388 calcium-transporting ATPase activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008022 protein C-terminus binding
GO:0016787 hydrolase activity
GO:0019899 enzyme binding
GO:0031775 lutropin-choriogonadotropic hormone receptor binding
GO:0044548 S100 protein binding
GO:0046872 metal ion binding
GO:0086039 calcium-transporting ATPase activity involved in regulation of cardiac muscle cell membrane potential

Biological Process:
GO:0002026 regulation of the force of heart contraction
GO:0006811 ion transport
GO:0006816 calcium ion transport
GO:0006874 cellular calcium ion homeostasis
GO:0006984 ER-nucleus signaling pathway
GO:0006996 organelle organization
GO:0007155 cell adhesion
GO:0008544 epidermis development
GO:0010460 positive regulation of heart rate
GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling
GO:0014883 transition between fast and slow fiber
GO:0014898 cardiac muscle hypertrophy in response to stress
GO:0032469 endoplasmic reticulum calcium ion homeostasis
GO:0032470 positive regulation of endoplasmic reticulum calcium ion concentration
GO:0032496 response to lipopolysaccharide
GO:0033292 T-tubule organization
GO:0034220 ion transmembrane transport
GO:0034599 cellular response to oxidative stress
GO:0034976 response to endoplasmic reticulum stress
GO:0045822 negative regulation of heart contraction
GO:0055119 relaxation of cardiac muscle
GO:0070296 sarcoplasmic reticulum calcium ion transport
GO:0070588 calcium ion transmembrane transport
GO:0086036 regulation of cardiac muscle cell membrane potential
GO:0098909 regulation of cardiac muscle cell action potential involved in regulation of contraction
GO:0099132 ATP hydrolysis coupled cation transmembrane transport
GO:1903233 regulation of calcium ion-dependent exocytosis of neurotransmitter
GO:1903515 calcium ion transport from cytosol to endoplasmic reticulum
GO:1903779 regulation of cardiac conduction
GO:1990036 calcium ion import into sarcoplasmic reticulum

Cellular Component:
GO:0005654 nucleoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005887 integral component of plasma membrane
GO:0012506 vesicle membrane
GO:0014801 longitudinal sarcoplasmic reticulum
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016529 sarcoplasmic reticulum
GO:0031095 platelet dense tubular network membrane
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0032991 macromolecular complex
GO:0033017 sarcoplasmic reticulum membrane
GO:0048471 perinuclear region of cytoplasm
GO:0090534 calcium ion-transporting ATPase complex
GO:0097470 ribbon synapse
GO:0014704 intercalated disc


-  Descriptions from all associated GenBank mRNAs
  M23114 - Homo sapiens calcium-ATPase (HK1) mRNA, complete cds.
LP895255 - Sequence 119 from Patent EP3253886.
BC035588 - Homo sapiens ATPase, Ca++ transporting, cardiac muscle, slow twitch 2, mRNA (cDNA clone MGC:45367 IMAGE:5503508), complete cds.
M23115 - Homo sapiens calcium-ATPase (HK2) mRNA, complete cds.
CU690124 - Synthetic construct Homo sapiens gateway clone IMAGE:100020537 5' read ATP2A2 mRNA.
KU177929 - Homo sapiens ATPase Ca++ transporting cardiac muscle slow twitch 2 isoform 1 (ATP2A2) mRNA, partial cds.
KU177930 - Homo sapiens ATPase Ca++ transporting cardiac muscle slow twitch 2 isoform 2 (ATP2A2) mRNA, complete cds, alternatively spliced.
KU177931 - Homo sapiens ATPase Ca++ transporting cardiac muscle slow twitch 2 isoform 3 (ATP2A2) mRNA, complete cds, alternatively spliced.
AK293877 - Homo sapiens cDNA FLJ55676 complete cds, highly similar to Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (EC 3.6.3.8).
BX648282 - Homo sapiens mRNA; cDNA DKFZp686P0211 (from clone DKFZp686P0211).
AY186578 - Homo sapiens sarco/endoplasmic reticulum calcium ATPase 2c (ATP2A2) mRNA, partial cds; alternatively spliced.
JD199052 - Sequence 180076 from Patent EP1572962.
JD083045 - Sequence 64069 from Patent EP1572962.
JD091756 - Sequence 72780 from Patent EP1572962.
JD088633 - Sequence 69657 from Patent EP1572962.
JD155974 - Sequence 136998 from Patent EP1572962.
JD534932 - Sequence 515956 from Patent EP1572962.
JD394521 - Sequence 375545 from Patent EP1572962.
JD224699 - Sequence 205723 from Patent EP1572962.
AK095382 - Homo sapiens cDNA FLJ38063 fis, clone CTONG2015091.
AK000300 - Homo sapiens cDNA FLJ20293 fis, clone HEP05659.
AL117505 - Homo sapiens mRNA; cDNA DKFZp434E1835 (from clone DKFZp434E1835).
BC065753 - Homo sapiens cDNA clone IMAGE:4272109, partial cds.
JD504555 - Sequence 485579 from Patent EP1572962.
JD310360 - Sequence 291384 from Patent EP1572962.
JD193259 - Sequence 174283 from Patent EP1572962.
JD024730 - Sequence 5754 from Patent EP1572962.
JD371009 - Sequence 352033 from Patent EP1572962.
JD030715 - Sequence 11739 from Patent EP1572962.
JD419226 - Sequence 400250 from Patent EP1572962.
JD299857 - Sequence 280881 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04020 - Calcium signaling pathway
hsa04260 - Cardiac muscle contraction
hsa05010 - Alzheimer's disease
hsa05410 - Hypertrophic cardiomyopathy (HCM)
hsa05412 - Arrhythmogenic right ventricular cardiomyopathy (ARVC)
hsa05414 - Dilated cardiomyopathy

Reactome (by CSHL, EBI, and GO)

Protein P16615 (Reactome details) participates in the following event(s):

R-HSA-427910 ATP2A1-3 transport Ca2+ from cytosol to ER lumen
R-HSA-418365 ATP2A1-3 transport cytosolic Ca2+ to dense tubular network lumen
R-HSA-936837 Ion transport by P-type ATPases
R-HSA-5578775 Ion homeostasis
R-HSA-418359 Reduction of cytosolic Ca++ levels
R-HSA-983712 Ion channel transport
R-HSA-5576891 Cardiac conduction
R-HSA-418360 Platelet calcium homeostasis
R-HSA-382551 Transport of small molecules
R-HSA-397014 Muscle contraction
R-HSA-418346 Platelet homeostasis
R-HSA-109582 Hemostasis

-  Other Names for This Gene
  Alternate Gene Symbols: A6NDN7, AT2A2_HUMAN, ATP2B, B4DF05, NM_170665, P16614, P16615, Q86VJ2, uc001tqk.1, uc001tqk.2, uc001tqk.3, uc001tqk.4, uc001tqk.5, uc001tqk.6
UCSC ID: uc001tqk.6
RefSeq Accession: NM_170665
Protein: P16615 (aka AT2A2_HUMAN or ATA2_HUMAN)
CCDS: CCDS9143.1, CCDS9144.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.