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
ID:AT2A2_HUMAN DESCRIPTION: RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 2; Short=SERCA2; Short=SR Ca(2+)-ATPase 2; EC=18.104.22.168; 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";
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.
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.
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