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]

ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:16402920).
Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335).
Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335).
Isoform 2: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca2+ signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca2+ spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca2+ signaling cascades that promote osteoclast differentiation and activation.

Autophagosome assembly Source: UniProtKB
Autophagosome membrane docking Source: UniProtKB
Calcium ion import into sarcoplasmic reticulum Source: BHF-UCL
Calcium ion transmembrane transport Source: BHF-UCL
Calcium ion transport from cytosol to endoplasmic reticulum Source: BHF-UCL
Cardiac muscle hypertrophy in response to stress Source: Ensembl
Cell adhesion Source: ProtInc
Cellular calcium ion homeostasis Source: BHF-UCL
Cellular response to heat Source: Ensembl
Cellular response to oxidative stress Source: Ensembl
Endoplasmic reticulum calcium ion homeostasis Source: BHF-UCL
Epidermis development Source: ProtInc
ER-nucleus signaling pathway Source: Ensembl
Ion transmembrane transport Source: Reactome
Mitochondrion-endoplasmic reticulum membrane tethering Source: UniProtKB
Negative regulation of heart contraction Source: Ensembl
Negative regulation of receptor binding Source: ARUK-UCL
Organelle localization by membrane tethering Source: UniProtKB
Positive regulation of endoplasmic reticulum calcium ion concentration Source: BHF-UCL
Positive regulation of heart rate Source: BHF-UCL
Regulation of calcium ion-dependent exocytosis of neurotransmitter Source: Ensembl
Regulation of cardiac conduction Source: Reactome
Regulation of cardiac muscle cell action potential involved in regulation of contraction Source: BHF-UCL
Regulation of cardiac muscle cell membrane potential Source: BHF-UCL
Regulation of cardiac muscle contraction by calcium ion signaling Source: BHF-UCL
Regulation of the force of heart contraction Source: Ensembl
Relaxation of cardiac muscle Source: BHF-UCL
Response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Response to lipopolysaccharide Source: Ensembl
Sarcoplasmic reticulum calcium ion transport Source: BHF-UCL
Skeletal muscle contraction Source: Ensembl
Transition between fast and slow fiber Source: Ensembl
T-tubule organization Source: Ensembl

Endoplasmic reticulum membrane; Sarcoplasmic reticulum membrane

Acrokeratosis verruciformis (AKV): 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.
Darier disease (DD): 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.

Cytoplasmic: 1-48 aa
Helical: 49-69 aa
Lumenal: 70-89 aa
Helical: 90-110 aa
Cytoplasmic: 111-253 aa
Helical: 254-273 aa
Lumenal: 274-295 aa
Helical: 296-313 aa
Cytoplasmic: 314-756 aa
Helical: 757-776 aa
Lumenal: 777-786 aa
Helical: 787-807 aa
Cytoplasmic: 808-827 aa
Helical: 828-850 aa
Lumenal: 851-896 aa
Helical: 897-916 aa
Cytoplasmic: 917-929 aa
Helical: 930-948 aa
Lumenal: 949-963 aa
Helical: 964-984 aa
Cytoplasmic: 985-1042 aa

Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity.
Serotonylated on Gln residues by TGM2 in response to hypoxia, leading to its inactivation.