Protein detail
AT2A2
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase)
Protein symbol AT2A2 | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count 10 | Protein classification Disease related genesEnzymesEssential proteinsFDA approved drug targetsHuman disease related genesMetabolic proteinsPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase)
Protein Class
Disease related genesEnzymesEssential proteinsFDA approved drug targetsHuman disease related genesMetabolic proteinsPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function
- Predicted intracellular proteins
- Enzymes
- ENZYME proteins
- Human disease related genes:Congenital malformations:Congenital malformations of skin
- Transporters:Primary Active Transporters
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
49..69; Helical; Name=1; 90..110; Helical; Name=2; 254..273; Helical; Name=3; 296..313; Helical; Name=4; 757..776; Helical; Name=5; 787..807; Helical; Name=6; 828..850; Helical; Name=7; 897..916; Helical; Name=8; 930..948; Helical; Name=9; 964..984; Helical; Name=10
Transmembrane Count
10
Ensembl
Entrez Gene Symbol
Gene Synonym
ATP2BDARSERCA2
Gene Description
ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2
Chromosome
12
Position
110280756-110351093
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Enzymes
- ENZYME proteins
- Human disease related genes:Congenital malformations:Congenital malformations of skin
- Transporters:Primary Active Transporters
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
- GO:0005783 endoplasmic reticulum
- GO:0005789 endoplasmic reticulum membrane
- GO:0005886 plasma membrane
- GO:0014704 intercalated disc
- GO:0014801 longitudinal sarcoplasmic reticulum
- GO:0016020 membrane
- GO:0016529 sarcoplasmic reticulum
- GO:0031095 platelet dense tubular network membrane
- GO:0033017 sarcoplasmic reticulum membrane
- GO:0090534 calcium ion-transporting ATPase complex
- GO:0097470 ribbon synapse
Molecular Function
- GO:0005388 P-type calcium transporter activity
- GO:0005509 calcium ion binding
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0019899 enzyme binding
- GO:0044325 transmembrane transporter binding
- GO:0044548 S100 protein binding
- GO:0086039 P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential
- GO:0106222 lncRNA binding
Biological Process
KEGG
- hsa04020 Calcium signaling pathway
- KEGG:hsa04022 cGMP-PKG signaling pathway
- KEGG:hsa04024 cAMP signaling pathway
- KEGG:hsa04148 Efferocytosis
- KEGG:hsa04260 Cardiac muscle contraction
- KEGG:hsa04261 Adrenergic signaling in cardiomyocytes
- KEGG:hsa04380 Osteoclast differentiation
- KEGG:hsa04919 Thyroid hormone signaling pathway
- KEGG:hsa04972 Pancreatic secretion
- KEGG:hsa05010 Alzheimer disease
- KEGG:hsa05017 Spinocerebellar ataxia
- KEGG:hsa05022 Pathways of neurodegeneration - multiple diseases
- KEGG:hsa05410 Hypertrophic cardiomyopathy
- KEGG:hsa05412 Arrhythmogenic right ventricular cardiomyopathy
- KEGG:hsa05414 Dilated cardiomyopathy
- KEGG:hsa05415 Diabetic cardiomyopathy
Reactome
- R-hsa-5576891 cardiac conduction
- R-hsa-109582 hemostasis
- R-hsa-983712 ion channel transport
- R-hsa-5578775 ion homeostasis
- R-hsa-936837 ion transport by p type atpases
- R-hsa-397014 muscle contraction
- R-hsa-418360 platelet calcium homeostasis
- R-hsa-418346 platelet homeostasis
- R-hsa-1912422 pre notch expression and processing
- R-hsa-1912420 pre notch processing in golgi
- R-hsa-418359 reduction of cytosolic ca levels
- R-hsa-157118 signaling by notch
- R-hsa-382551 transport of small molecules
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
8 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| ATP2A2 | CAMK2A | Q9UQM7 | S | 38 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapper | KEA:7929371ProtMapper:7929371SIGNOR:7929371HPRD:7929371 |
| ATP2A2 | CAMK4 | Q16566 | S | 178 | phosphorylation | PhosphoNetworks | |
| ATP2A2 | AURKB | Q96GD4 | S | 663 | phosphorylation | KEA | KEA:15302935KEA:17081983KEA:14722118 |
| ATP2A2 | CAMK2B | Q13554 | S | 38 | phosphorylation | KEA | KEA:7929371 |
| ATP2A2 | CAMK2D | Q13557 | S | 38 | phosphorylation | KEA | KEA:7929371 |
| ATP2A2 | CAMK2G | Q13555 | S | 38 | phosphorylation | KEA | KEA:7929371 |
| ATP2A2 | PRKDC | P78527 | S | 38 | phosphorylation | KEA | KEA:17570479 |
| ATP2A2 | RPS6KA3 | P51812 | S | 38 | phosphorylation | KEA | KEA:17570479 |
Ligand-Receptor Signaling
20 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| transmembrane | transmembrane | UniProt_topology | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_keyword | No | No | No | No | No |
| transmembrane | transmembrane | TopDB | No | No | No | No | No |
| transmembrane | transmembrane | LOCATE | No | No | No | No | No |
| transmembrane | transmembrane | Ramilowski_location | No | No | No | No | No |
| transmembrane | transmembrane | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | Cellinker | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
| transmembrane | transmembrane_predicted | Phobius | No | No | No | No | No |
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Regulatory Interaction Network
8 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| HAX1 | O00165 | AT2A2 | P16615 | Yes | No | Yes | SIGNOR | SIGNOR:18971376 |
| MK09 | P45984 | AT2A2 | P16615 | Yes | Yes | No | SIGNOR | SIGNOR:33334123 |
| SRCH | P23327 | AT2A2 | P16615 | Yes | No | Yes | SIGNOR | SIGNOR:28784772 |
| GSK3B | P49841 | AT2A2 | P16615 | Yes | No | Yes | SIGNOR | SIGNOR:37291092 |
| PPLA | P26678 | AT2A2 | P16615 | Yes | No | Yes | WangKEGG-MEDICUSSIGNORHPRDBioGRIDSPIKE_LC | BioGRID:10809745BioGRID:11854448HPRD:11854448HPRD:11526231SIGNOR:12838339SPIKE_LC:16189514HPRD:10809745 |
| SARCO | O00631 | AT2A2 | P16615 | Yes | No | Yes | KEGG-MEDICUSSIGNOR | SIGNOR:23455424 |
| KCC2A | Q9UQM7 | AT2A2 | P16615 | Yes | Yes | No | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperHPRD-phos | SIGNOR:7929371HPRD-phos:7929371KEA:7929371ProtMapper:7929371HPRD:7929371 |
| PDE3A | Q14432 | AT2A2 | P16615 | Yes | No | Yes | SIGNOR | SIGNOR:25593322 |
Protein Complex Composition
Sequence, Structure & Domains
Sequences
Length
1,042
Mass
114,757
Sequence
MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSILTGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIAVWIINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQMSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVEKMNVFDTELKGLSKIERANACNSVIKQLMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGVKQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGTAVAICRRIGIFGQDEDVTSKAFTGREFDELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMGSGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMNKPPRNPKEPLISGWLFFRYLAIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMALSVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNYLEPGKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS
Alternative Products
Event=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; Name=2; Synonyms=ATP2A2A, Class 1, HK2, SERCA2a; IsoId=P16615-2; Sequence=VSP_000358; Name=3; Synonyms=SERCA2C; IsoId=P16615-3; Sequence=VSP_039393; Name=4; IsoId=P16615-4; Sequence=VSP_039392; Name=5; IsoId=P16615-5; Sequence=VSP_039394
Alternative Sequence
155..181; Missing (in isoform 4); 994..1042; GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS -> AILE (in isoform 2); 994..1042; GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS -> VLSSEL (in isoform 3); 994..1042; GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS -> DIIK (in isoform 5)
3D Structural Models
Turn
20..22; 118..121; 154..156; 178..181; 201..203; 275..277; 429..432; 489..492; 504..506; 648..650; 797..799; 813..817; 921..923
Helix
4..6; 9..15; 26..35; 49..56; 60..77; 86..88; 89..116; 142..144; 227..229; 231..241; 248..274; 278..280; 288..304; 311..328; 337..339; 341..344; 352..356; 404..406; 408..420; 440..451; 464..467; 470..478; 517..523; 538..553; 572..574; 580..586; 606..615; 628..637; 654..658; 662..671; 680..692; 704..706; 707..712; 724..729; 740..780; 788..796; 800..805; 806..808; 830..856; 867..870; 872..874; 888..891; 894..912; 926..928; 930..948; 952..955; 963..973; 975..989; 1016..1030
Beta Strand
78..80; 81..83; 126..131; 134..136; 138..141; 150..153; 161..171; 173..176; 187..189; 206..208; 213..216; 219..225; 281..284; 331..336; 347..350; 362..375; 377..384; 388..391; 395..397; 425..428; 433..438; 460..462; 479..488; 493..500; 511..515; 524..529; 532..535; 554..556; 559..568; 587..599; 619..623; 639..641; 651..653; 674..677; 697..701; 713..719; 731..734; 823..825; 859..861; 875..881; 882..884; 915..919; 949..951
3D Structure
Electron microscopy (12); X-ray crystallography (3)
Domain & Motif Annotations
Domain (CC)
Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation.; DOMAIN: PLN and SLN both have a single transmembrane helix; both occupy a similar binding site that is situated between the ATP2A2 transmembrane helices.
Region
575..594; Interaction with HAX1; 787..807; Interaction with PLN; 788..1042; Interaction with TMEM64 and PDIA3; 931..942; Interaction with PLN
Protein Families
- Cation transport ATPase (P-type) (TC 3.A.3) family
- Type IIA subfamily
Sequence Similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
Clinical Relevance
Disease Involvement
Disease variantEpilepsyFDA approved drug targets
Related Diseases
Biomarker
Phase 2; Discontinued in Phase 1
Drug Targets
FDA approved drug targets
Drugs
Antibody
Interaction Protein
ENSG00000136997ENSG00000164251
Interaction Count
2
Interaction Dataset
intact_biogrid