MGP Database

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MGP000245

UniProt Annotations

Entry Information
Gene NameATPase, Ca++ transporting, cardiac muscle, slow twitch 2
Protein EntryAT2A2_HUMAN
UniProt IDP16615
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Comment=SERCA2 transcripts differ only in their 3'-UTR region and are expressed in a tissue-specific manner.; Name=1; Synonyms=ATP2A2B, Class 2-4, HK1, SERCA2b; IsoId=P16615-1; Sequence=Displayed; Note=Ubiquitous housekeeping isoform.; Name=2; Synonyms=ATP2A2A, Class 1, HK2, SERCA2a; IsoId=P16615-2; Sequence=VSP_000358; Note=Cardiac/slow twitch, muscle specific isoform. Has a lower affinity for calcium and a higher catalytic turnover rate.; Name=3; Synonyms=SERCA2C; IsoId=P16615-3; Sequence=VSP_039393; Note=May be due to intron retention. Shows a lower apparent affinity for cytosolic calcium than isoform 2 and a catalytic turnover rate similar to isoform 1.; Name=4; IsoId=P16615-4; Sequence=VSP_039392; Note=No experimental confirmation available.; Name=5; IsoId=P16615-5; Sequence=VSP_039394; Note=No experimental confirmation available.;
Catalytic ActivityATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate + Ca(2+)(Side 2).
DiseaseAcrokeratosis 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. {ECO:0000269|PubMed:12542527}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseDarier 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. {ECO:0000269|PubMed:10080178, ECO:0000269|PubMed:10441323, ECO:0000269|PubMed:10441324, ECO:0000269|PubMed:10441325, ECO:0000269|PubMed:19995371}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationReversibly 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). {ECO:0000250}.
FunctionThis 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. {ECO:0000269|PubMed:16402920}.
InteractionP41143:OPRD1; NbExp=3; IntAct=EBI-358933, EBI-2624456;
PtmNitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity. {ECO:0000269|PubMed:16399855}.
Sequence CautionSequence=BAG57266.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily. {ECO:0000305}.
Subcellular LocationEndoplasmic reticulum membrane; Multi-pass membrane protein. Sarcoplasmic reticulum membrane; Multi-pass membrane protein.
SubunitAssociated with phospholamban (PLN) (By similarity). Isoform 1 interacts with TRAM2 (via C-terminus). Interacts with HAX1. Interacts with S100A8 and S100A9 (By similarity). Interacts with SLC35G1 and STIM1. {ECO:0000250, ECO:0000269|PubMed:14749390, ECO:0000269|PubMed:18971376, ECO:0000269|PubMed:22084111}.
Tissue SpecificityIsoform 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. {ECO:0000269|PubMed:10441324, ECO:0000269|PubMed:12659872, ECO:0000269|PubMed:16402920}.
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