ATP2A2
entrez
488
canonical
uniprot
P16615
canonical
ensembl
ENSG00000174437
resolver
ensp
ENSP00000311186
resolver
ensp
ENSP00000440045
resolver
ensp
ENSP00000449454
resolver
ensp
ENSP00000580650
resolver
genesymbol
ATP2A2
resolver
genesymbol_syn
ATP2B
resolver
hgnc
HGNC:812
resolver
uniprot
A0A0S2Z3L2
resolver
uniprot
A6NDN7
resolver
uniprot
B4DF05
resolver
uniprot
P16614
resolver
uniprot
Q86VJ2
resolver
uniprot_entry
A0A0S2Z3L2_HUMAN
resolver
uniprot_entry
AT2A2_HUMAN
resolver
uniprot_sec
A6NDN7
resolver
uniprot_sec
B4DF05
resolver
uniprot_sec
P16614
resolver
uniprot_sec
Q86VJ2
resolver
activity_regulation
ACTIVITY REGULATION: Has different conformational states with differential Ca2+ affinity. The E1 conformational state (active form) shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) affinity. Binding of ATP allosterically increases its affinity for subsequent binding of Ca2+ (By similarity). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. PLN inhibits ATP2A2 Ca(2+) affinity by disrupting its allosteric activation by ATP (By similarity). Inhibited by sarcolipin (SLN) and myoregulin (MRLN). The inhibition is blocked by VMP1 (PubMed:28890335). Enhanced by STRIT1/DWORF; STRIT1 increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (PubMed:33581112). Stabilizes SERCA2 in its E2 state (PubMed:28890335). {ECO:0000250|UniProtKB:O46674, ECO:0000250|UniProtKB:O55143, ECO:0000250|UniProtKB:P04191, ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:33581112}.
uniprot
proteins
amino_acid_sequence
MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSILTGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIAVWIINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQMSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVEKMNVFDTELKGLSKIERANACNSVIKQLMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGVKQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGTAVAICRRIGIFGQDEDVTSKAFTGREFDELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMGSGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMNKPPRNPKEPLISGWLFFRYLAIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMALSVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNYLEPGKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:10441323, ECO:0000269|PubMed:12542527}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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 intellectual disability, 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, ECO:0000269|PubMed:23356892, ECO:0000269|PubMed:28035777}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rhabdomyolysis 2 (RHABDO2) [MIM:621236]: An autosomal dominant disorder characterized by recurrent rhabdomyolysis, triggered predominantly by fever or infection. Rhabdomyolysis is the rapid breakdown of damaged or injured skeletal myofibres and may require intensive care management. Muscle breakdown results in release of myofibrillar content into the extracellular space and circulation, resulting in hyperCKemia (hyperCK) and myoglobinuria. {ECO:0000269|PubMed:39970126}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
7.2.2.10
uniprot
proteins
function
FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:12542527, 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). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}.; FUNCTION: [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) 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 Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. {ECO:0000250|UniProtKB:O55143}.
uniprot
proteins
mass_dalton
114757
uniprot
proteins
mutagenesis
MUTAGEN 256; /note="F->V: No effect on interaction with VMP1."; /evidence="ECO:0000269|PubMed:28890335
uniprot
proteins
post_translational_modification
PTM: Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity. {ECO:0000269|PubMed:16399855}.; PTM: Serotonylated on Gln residues by TGM2 in response to hypoxia, leading to its inactivation. {ECO:0000250|UniProtKB:O55143}.
uniprot
proteins
protein_family
Cation transport ATPase (P-type) (TC 3.A.3) family
uniprot
proteins
protein_family
Type IIA subfamily
uniprot
proteins
pubmed
10080178
uniprot
proteins
pubmed
10441323
uniprot
proteins
pubmed
10441324
uniprot
proteins
pubmed
10441325
uniprot
proteins
pubmed
12542527
uniprot
proteins
pubmed
12659872
uniprot
proteins
pubmed
12804600
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14749390
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16399855
uniprot
proteins
pubmed
16402920
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18971376
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19995371
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22084111
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23356892
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
25996873
uniprot
proteins
pubmed
27502484
uniprot
proteins
pubmed
28035777
uniprot
proteins
pubmed
2844796
uniprot
proteins
pubmed
28890335
uniprot
proteins
pubmed
31735293
uniprot
proteins
pubmed
33581112
uniprot
proteins
pubmed
36523160
uniprot
proteins
pubmed
39970126
uniprot
proteins
sequence_length
1042
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:O55143}; Multi-pass membrane protein {ECO:0000255}. Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:12804600}; Multi-pass membrane protein {ECO:0000255}. Note=Colocalizes with FLVCR2 at the mitochondrial-ER contact junction. {ECO:0000250|UniProtKB:O55143}.
uniprot
proteins
transmembrane_region
TRANSMEM 49..69; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 90..110; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 254..273; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 296..313; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 757..776; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 787..807; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 828..850; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 897..916; /note="Helical; Name=8"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 930..948; /note="Helical; Name=9"; /evidence="ECO:0000250|UniProtKB:P04191"; TRANSMEM 964..984; /note="Helical; Name=10"; /evidence="ECO:0000250|UniProtKB:P04191
uniprot
proteins