InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ATP2A2

Summary

InnateDB Protein

IDBP-588695.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ATP2A2

Protein Name

ATPase, Ca++ transporting, cardiac muscle, slow twitch 2

Synonyms

ATP2B; DAR; DD; SERCA2;

Species

Homo sapiens

Ensembl Protein

ENSP00000440045

InnateDB Gene

IDBG-56943 (ATP2A2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:16402920}.

Subcellular Localization

Endoplasmic reticulum membrane; Multi-pass membrane protein. Sarcoplasmic reticulum membrane; Multi-pass membrane protein.

Disease Associations

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. {ECO:0000269PubMed:12542527}. 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. {ECO:0000269PubMed:10080178, ECO:0000269PubMed:10441323, ECO:0000269PubMed:10441324, ECO:0000269PubMed:10441325, ECO:0000269PubMed:19995371}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:10441324, ECO:0000269PubMed:12659872, ECO:0000269PubMed:16402920}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 48 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	48 [view]
Protein-Protein	48 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0005388	calcium-transporting ATPase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0019829	cation-transporting ATPase activity
GO:0019899	enzyme 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:0006810	transport
GO:0006812	cation transport
GO:0006816	calcium ion transport
GO:0006874	cellular calcium ion homeostasis
GO:0006984	ER-nucleus signaling pathway
GO:0007155	cell adhesion
GO:0007596	blood coagulation
GO:0008152	metabolic process
GO:0008544	epidermis development
GO:0010460	positive regulation of heart rate
GO:0034220	ion transmembrane transport
GO:0045822	negative regulation of heart contraction
GO:0055085	transmembrane transport
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

Cellular Component

GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005887	integral component of plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016529	sarcoplasmic reticulum
GO:0031095	platelet dense tubular network membrane
GO:0033017	sarcoplasmic reticulum membrane
GO:0043231	intracellular membrane-bounded organelle

Protein Structure and Domains

PDB ID

InterPro

IPR001757 Cation-transporting P-type ATPase
IPR004014 Cation-transporting P-type ATPase, N-terminal
IPR005782 Calcium-transporting P-type ATPase, subfamily IIA, SERCA-type
IPR006068 Cation-transporting P-type ATPase, C-terminal
IPR008250 P-type ATPase, A domain
IPR023214 HAD-like domain
IPR023299 P-type ATPase, cytoplasmic domain N

PFAM

PF00690
PF00689
PF00122
PF00702
PF08282
PF13419

PRINTS

PR00119
PR00120

PIRSF

SMART

SM00831

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt