P48452
SS
Gene name |
PPP3CA |
Protein name |
Protein phosphatase 3 catalytic subunit alpha |
Names |
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 |
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:286852 |
EC number |
3.1.3.16: Phosphoric monoester hydrolases |
Protein Class |
|
Descriptions
Calcium-dependent, calmodulin-stimulated protein phosphatase calcineurin (CN) plays a role in the transduction of intracellular Ca2+-dependent signals. CN is a heterodimer composed of a catalytic subunit A (CNA) and an essential regulatory subunit B (CNB). <br>CNA contains two autoinhibitory regions, which interfere with the function of the catalytic domain: autoinhibitory segment (AIS) and autoinhibitory domain (AID). The AIS interacts with a hydrophobic intersubunit groove formed at the junction of CNA and CNB, and disruption of the AIS interaction results in partial stimulation of CN activity. In addition, the binding partner calmodulin regulates the orientation of AID with respect to the catalytic core, resulting in incomplete activation of CN.
Autoinhibitory domains (AIDs)
Target domain |
93-293 (Calcineurin-like phosphoesterase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Tokoyoda K et al. (2000) "Synergism between the calmodulin-binding and autoinhibitory domains on calcineurin is essential for the induction of their phosphatase activity", The Journal of biological chemistry, 275, 11728-34
- Li SJ et al. (2016) "Cooperative autoinhibition and multi-level activation mechanisms of calcineurin", Cell research, 26, 336-49
- Rumi-Masante J et al. (2012) "Structural basis for activation of calcineurin by calmodulin", Journal of molecular biology, 415, 307-17
- Kissinger CR et al. (1995) "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex", Nature, 378, 641-4
- Ye Q et al. (2008) "The complex structure of calmodulin bound to a calcineurin peptide", Proteins, 73, 19-27
Autoinhibited structure
Activated structure
4 structures for P48452
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1TCO | X-ray | 250 A | A | 18-392 | PDB |
| 2F2O | X-ray | 217 A | A/B | 389-413 | PDB |
| 2F2P | X-ray | 260 A | A/B | 389-413 | PDB |
| AF-P48452-F1 | Predicted | AlphaFoldDB |
52 variants for P48452
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs436106481 | 2 | S>C | No | EVA | |
| rs465810065 | 2 | S>T | No | EVA | |
| rs469876777 | 17 | V>E | No | EVA | |
| rs437064967 | 19 | K>T | No | EVA | |
| rs436703339 | 37 | N>H | No | EVA | |
| rs467882213 | 45 | I>L | No | EVA | |
| rs439099605 | 82 | D>H | No | EVA | |
| rs447846985 | 96 | F>L | No | EVA | |
| rs450931577 | 169 | K>E | No | EVA | |
| rs719083141 | 173 | R>H | No | EVA | |
| rs469445249 | 182 | F>V | No | EVA | |
| rs799400436 | 183 | D>A | No | EVA | |
| rs433412812 | 189 | A>V | No | EVA | |
| rs472310983 | 200 | G>S | No | EVA | |
| rs451760323 | 202 | L>* | No | EVA | |
| rs434241015 | 204 | P>A | No | EVA | |
| rs452949529 | 204 | P>Q | No | EVA | |
| rs379918899 | 208 | T>S | No | EVA | |
| rs441632256 | 212 | I>S | No | EVA | |
| rs448491927 | 319 | A>D | No | EVA | |
| rs470200492 | 320 | A>P | No | EVA | |
| rs482254840 | 320 | A>V | No | EVA | |
| rs453347690 | 332 | R>S | No | EVA | |
| rs434960586 | 332 | R>T | No | EVA | |
| rs464446639 | 332 | R>W | No | EVA | |
| rs480074592 | 374 | D>A | No | EVA | |
| rs464632979 | 388 | T>A | No | EVA | |
| rs434971501 | 388 | T>K | No | EVA | |
| rs447101418 | 390 | A>P | No | EVA | |
| rs468859496 | 391 | A>P | No | EVA | |
| rs454492123 | 392 | R>G | No | EVA | |
| rs476180358 | 395 | V>A | No | EVA | |
| rs476180358 | 395 | V>E | No | EVA | |
| rs452219971 | 397 | R>K | No | EVA | |
| rs470821530 | 398 | N>K | No | EVA | |
| rs440946510 | 400 | I>T | No | EVA | |
| rs474892142 | 404 | G>R | No | EVA | |
| rs441990444 | 409 | V>G | No | EVA | |
| rs433988707 | 443 | T>I | No | EVA | |
| rs481715632 | 455 | D>V | No | EVA | |
| rs467017405 | 505 | S>P | No | EVA | |
| rs433917389 | 510 | T>P | No | EVA | |
| rs438211361 | 516 | N>K | No | EVA | |
| rs456708605 | 517 | S>R | No | EVA | |
| rs472010091 | 518 | S>G | No | EVA | |
| rs439128325 | 518 | S>R | No | EVA | |
| rs472010091 | 518 | S>R | No | EVA | |
| rs454360602 | 519 | N>K | No | EVA | |
| rs472815842 | 521 | Q>L | No | EVA | |
| rs461700120 | 522 | Q>C | No | EVA | |
| rs439925381 | 522 | Q>G | No | EVA | |
| rs461700120 | 522 | Q>W | No | EVA |
No associated diseases with P48452
13 regional properties for P48452
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| conserved_site | Actinin-type actin-binding domain, conserved site | 34 - 43 | IPR001589-1 |
| conserved_site | Actinin-type actin-binding domain, conserved site | 108 - 132 | IPR001589-2 |
| domain | Calponin homology domain | 32 - 136 | IPR001715-1 |
| domain | Calponin homology domain | 145 - 251 | IPR001715-2 |
| repeat | Spectrin repeat | 276 - 384 | IPR002017-1 |
| repeat | Spectrin repeat | 395 - 499 | IPR002017-2 |
| repeat | Spectrin repeat | 511 - 620 | IPR002017-3 |
| repeat | Spectrin repeat | 633 - 733 | IPR002017-4 |
| domain | EF-hand domain | 747 - 823 | IPR002048 |
| domain | EF-hand, Ca insensitive | 823 - 889 | IPR014837 |
| repeat | Spectrin/alpha-actinin | 278 - 623 | IPR018159-1 |
| repeat | Spectrin/alpha-actinin | 634 - 733 | IPR018159-2 |
| binding_site | EF-Hand 1, calcium-binding site | 760 - 772 | IPR018247 |
Functions
| Description | ||
|---|---|---|
| EC Number | 3.1.3.16 | Phosphoric monoester hydrolases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| calcineurin complex | A heterodimeric calcium ion and calmodulin dependent protein phosphatase composed of catalytic and regulatory subunits; the regulatory subunit is very similar in sequence to calmodulin. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| dendritic spine | A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity. |
| sarcolemma | The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers. |
| Z disc | Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| calmodulin binding | Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states. |
| calmodulin-dependent protein phosphatase activity | Catalysis of the reaction |
| metal ion binding | Binding to a metal ion. |
| myosin phosphatase activity | Catalysis of the reaction |
16 GO annotations of biological process
| Name | Definition |
|---|---|
| calcineurin-NFAT signaling cascade | Any intracellular signal transduction in which the signal is passed on within the cell by activation of a member of the NFAT protein family as a consequence of NFAT dephosphorylation by Ca(2+)-activated calcineurin. The cascade begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin dephosphorylates multiple phosphoserine residues on NFAT, resulting in the translocation of NFAT to the nucleus. The cascade ends with regulation of transcription by NFAT. The calcineurin-NFAT cascade lies downstream of many cell surface receptors, including G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) that signal to mobilize calcium ions (Ca2+). |
| dephosphorylation | The process of removing one or more phosphoric (ester or anhydride) residues from a molecule. |
| epidermis development | The process whose specific outcome is the progression of the epidermis over time, from its formation to the mature structure. The epidermis is the outer epithelial layer of an animal, it may be a single layer that produces an extracellular material (e.g. the cuticle of arthropods) or a complex stratified squamous epithelium, as in the case of many vertebrate species. |
| keratinocyte differentiation | The process in which a relatively unspecialized cell acquires specialized features of a keratinocyte. |
| modulation of chemical synaptic transmission | Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission. |
| negative regulation of signaling | Any process that stops, prevents, or reduces the frequency, rate or extent of a signaling process. |
| positive regulation of activated T cell proliferation | Any process that activates or increases the rate or extent of activated T cell proliferation. |
| positive regulation of glomerulus development | Any process that increases the rate, frequency or extent of glomerulus development, the progression of the glomerulus over time from its initial formation until its mature state. The glomerulus is a capillary tuft surrounded by Bowman's capsule in nephrons of the vertebrate kidney. |
| positive regulation of osteoblast differentiation | Any process that activates or increases the frequency, rate or extent of osteoblast differentiation. |
| positive regulation of osteoclast differentiation | Any process that activates or increases the frequency, rate or extent of osteoclast differentiation. |
| positive regulation of saliva secretion | Any process that activates or increases the frequency, rate or extent of the regulated release of saliva. |
| protein dephosphorylation | The process of removing one or more phosphoric residues from a protein. |
| regulation of cell proliferation involved in kidney morphogenesis | Any process that modulates the frequency, rate or extent of cell proliferation that contributes to the shaping of the kidney. |
| renal filtration | A renal system process in which fluid circulating through the body is filtered through a barrier system. |
| response to calcium ion | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a calcium ion stimulus. |
| skeletal muscle fiber development | The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast. |
13 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P23287 | CNA1 | Serine/threonine-protein phosphatase 2B catalytic subunit A1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q27889 | Pp2B-14D | Serine/threonine-protein phosphatase 2B catalytic subunit 2 | Drosophila melanogaster (Fruit fly) | SS |
| P48456 | CanA1 | Serine/threonine-protein phosphatase 2B catalytic subunit 1 | Drosophila melanogaster (Fruit fly) | SS |
| Q9VXF1 | CanA-14F | Serine/threonine-protein phosphatase 2B catalytic subunit 3 | Drosophila melanogaster (Fruit fly) | SS |
| P16298 | PPP3CB | Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform | Homo sapiens (Human) | EV |
| P48454 | PPP3CC | Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform | Homo sapiens (Human) | SS |
| Q08209 | PPP3CA | Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform | Homo sapiens (Human) | EV |
| P48453 | Ppp3cb | Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform | Mus musculus (Mouse) | SS |
| P48455 | Ppp3cc | Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform | Mus musculus (Mouse) | PR |
| P63328 | Ppp3ca | Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform | Mus musculus (Mouse) | EV |
| P20651 | Ppp3cb | Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform | Rattus norvegicus (Rat) | SS |
| P63329 | Ppp3ca | Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform | Rattus norvegicus (Rat) | SS |
| Q0G819 | tax-6 | Serine/threonine-protein phosphatase 2B catalytic subunit | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSEPKAIDPK | LSTTDRVVKA | VPFPPSHRLT | AKEVFDNDGK | PRVDILKAHL | MKEGRLEETV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| ALRIITEGAS | ILRQEKNLLD | IDAPVTVCGD | IHGQFFDLMK | LFEVGGSPAN | TRYLFLGDYV |
| 130 | 140 | 150 | 160 | 170 | 180 |
| DRGYFSIECV | LYLWALKILY | PKTLFLLRGN | HECRHLTEYF | TFKQECKIKY | SERVYDACMD |
| 190 | 200 | 210 | 220 | 230 | 240 |
| AFDCLPLAAL | MNQQFLCVHG | GLSPEINTLD | DIRKLDRFKE | PPAYGPMCDI | LWSDPLEDFG |
| 250 | 260 | 270 | 280 | 290 | 300 |
| NEKTQEHFTH | NTVRGCSYFY | SYPAVCEFLQ | HNNLLSILRA | HEAQDAGYRM | YRKSQTTGFP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SLITIFSAPN | YLDVYNNKAA | VLKYENNVMN | IRQFNCSPHP | YWLPNFMDVF | TWSLPFVGEK |
| 370 | 380 | 390 | 400 | 410 | 420 |
| VTEMLVNVLN | ICSDDELGSE | EDGFDGATAA | ARKEVIRNKI | RAIGKMARVF | SVLREESESV |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LTLKGLTPTG | MLPSGVLSGG | KQTLQSATVE | AIEADEAIKG | FSPQHKITSF | EEAKGLDRIN |
| 490 | 500 | 510 | 520 | ||
| ERMPPRRDAM | PSDANLNSIN | KALASETNGT | DSNGSNSSNI | Q |