| IED ID | IndEnz0018001253 |
| Enzyme Type ID | peroxidase001253 |
| Protein Name |
Protein phosphatase 3 catalytic subunit alpha EC 3.1.3.16 CAM-PRP catalytic subunit Calcineurin A alpha Calmodulin-dependent calcineurin A subunit alpha isoform CNA alpha Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform |
| Gene Name | Ppp3ca Calna |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MSEPKAIDPKLSTTDRVVKAVPFPPSHRLTAKEVFDNDGKPRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFGNEKTQEHFTHNTVRGCSYFYSYPAVCDFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHPYWLPNFMDVFTWSLPFVGEKVTEMLVNVLNICSDDELGSEEDGFDGATAAARKEVIRNKIRAIGKMARVFSVLREESESVLTLKGLTPTGMLPSGVLSGGKQTLQSATVEAIEADEAIKGFSPQHKITSFEEAKGLDRINERMPPRRDAMPSDANLNSINKALASETNGTDSNGSNSSNIQ |
| Enzyme Length | 521 |
| Uniprot Accession Number | P63328 |
| Absorption | |
| Active Site | ACT_SITE 151; /note=Proton donor; /evidence=ECO:0000250|UniProtKB:Q08209 |
| Activity Regulation | ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:26794871). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:26794871). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:26794871). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:26794871). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By similarity). {ECO:0000250|UniProtKB:P48452, ECO:0000269|PubMed:26794871}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; Evidence={ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:7791792}; CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16; Evidence={ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:7791792}; |
| DNA Binding | |
| EC Number | 3.1.3.16 |
| Enzyme Function | FUNCTION: Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:7791792, PubMed:26794871). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (By similarity). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (By similarity). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (By similarity). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (By similarity). Dephosphorylates and inactivates transcription factor ELK1 (By similarity). Dephosphorylates DARPP32 (By similarity). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (By similarity). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (PubMed:15509543). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (PubMed:16735444). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (PubMed:21435446). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (PubMed:10200317). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (PubMed:19626032). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (PubMed:16286645). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (PubMed:16968888). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (PubMed:12773574). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (PubMed:26029823). Required for antigen-specific T-cell proliferation response (PubMed:8627154). {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63329, ECO:0000250|UniProtKB:Q08209, ECO:0000269|PubMed:10200317, ECO:0000269|PubMed:12773574, ECO:0000269|PubMed:15509543, ECO:0000269|PubMed:16286645, ECO:0000269|PubMed:16735444, ECO:0000269|PubMed:16968888, ECO:0000269|PubMed:19626032, ECO:0000269|PubMed:21435446, ECO:0000269|PubMed:26029823, ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:7791792, ECO:0000269|PubMed:8627154}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (1); Beta strand (15); Chain (1); Compositional bias (1); Helix (16); Initiator methionine (1); Metal binding (7); Modified residue (4); Motif (1); Mutagenesis (5); Region (7); Site (1); Turn (6) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Calmodulin-binding;Cell junction;Cell membrane;Cell projection;Cytoplasm;Direct protein sequencing;Hydrolase;Iron;Membrane;Metal-binding;Nitration;Phosphoprotein;Protein phosphatase;Reference proteome;Synapse;Zinc |
| Interact With | Q3U182 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16286645, ECO:0000269|PubMed:16968888}. Cell membrane {ECO:0000250|UniProtKB:Q08209}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q08209}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P63329}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P63329}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q08209}. Note=Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle. Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation. {ECO:0000250|UniProtKB:P63329, ECO:0000250|UniProtKB:Q08209}. |
| Modified Residue | MOD_RES 2; /note=N-acetylserine; /evidence=ECO:0000250|UniProtKB:Q08209; MOD_RES 224; /note=3'-nitrotyrosine; /evidence=ECO:0007744|PubMed:16800626; MOD_RES 469; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P63329; MOD_RES 492; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21183079 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 4ORB; |
| Mapped Pubmed ID | 10767319; 10839803; 10862698; 11015619; 11062266; 11123943; 11217851; 11257222; 11279073; 11733061; 11782539; 11842093; 11981809; 12370307; 12377773; 12414688; 12466851; 12515860; 12520002; 12574411; 12617961; 12660151; 12808150; 12851457; 1318721; 14610273; 14656927; 14741691; 14767060; 15082723; 15543153; 15590926; 15665106; 15880107; 16024798; 16512683; 16602821; 16615898; 16635246; 16717086; 16793906; 16931796; 17072859; 17114649; 17198697; 17229811; 17428973; 17475677; 17587059; 17640527; 17684059; 17699657; 17785681; 17878357; 17881460; 17967808; 17978097; 18077674; 18086917; 18199592; 18544643; 18586679; 18639592; 18676376; 18815128; 19075228; 19129256; 19188439; 19203999; 19287093; 19351742; 19455133; 19478199; 19527231; 19538478; 19560418; 19710169; 19717566; 19733666; 19747209; 19769983; 19782130; 19799774; 19854199; 19861587; 19879877; 19907005; 19907416; 20032460; 20153290; 20351294; 20359506; 20402674; 20601385; 20647544; 20810903; 20937869; 20970476; 21059644; 21076497; 21233454; 21267068; 21421818; 21540458; 21622531; 21677750; 21689596; 21690297; 21986493; 22060133; 22153079; 22164265; 22239345; 22343722; 22495310; 22560297; 22688515; 22984995; 23261540; 23300663; 23407945; 23638102; 23733189; 23744075; 23825400; 23996002; 24107951; 24161931; 24291696; 24336651; 24448406; 24498049; 24526353; 24657879; 24672054; 24721909; 24835995; 24838101; 24952961; 25051958; 25193101; 2556704; 26031702; 26299309; 26411342; 26430214; 26514267; 26724383; 27009276; 27171192; 27301880; 27307045; 27892464; 28062573; 28126489; 28826478; 29444424; 29457983; 30274399; 30699351; 30995482; 31626368; 31637311; 32376900; 33879538; 8155595; 8187553; 8631904; 9017603; 9084440; 9489697; 9489698; 9515963; 9515964; |
| Motif | MOTIF 307..311; /note=SAPNY motif; /evidence=ECO:0000250|UniProtKB:Q08209 |
| Gene Encoded By | |
| Mass | 58,644 |
| Kinetics | |
| Metal Binding | METAL 90; /note="Iron"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB"; METAL 92; /note="Iron; via tele nitrogen"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB"; METAL 118; /note="Iron"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB"; METAL 118; /note="Zinc"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB"; METAL 150; /note="Zinc"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB"; METAL 199; /note="Zinc; via tele nitrogen"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB"; METAL 281; /note="Zinc; via pros nitrogen"; /evidence="ECO:0000269|PubMed:26794871, ECO:0007744|PDB:4ORB" |
| Rhea ID | RHEA:20629; RHEA:47004 |
| Cross Reference Brenda |