P63329

SS
Gene name
Ppp3ca (Calna)
Protein name
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
Names
CAM-PRP catalytic subunit, Calmodulin-dependent calcineurin A subunit alpha isoform
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:24674
EC number
3.1.3.16: Phosphoric monoester hydrolases
Protein Class

Descriptions

Calcium-dependent, calmodulin-stimulated protein phosphatase (PPP3CA) plays a role in the transduction of intracellular Ca2+-dependent signals. This protein contains two autoinhibitory regions, which interfere with the function of the catalytic domain: autoinhibitory segment(407-414, AIS), autoinhibitory domain(467-487, AUTOINHIBITORY_DOMAIN(AID)). AIS interact with a hydrophobic groove formed at the junction of CNA and CNB subunits, and the predominantly hydrophobic interactions recruiting AIS mainly involve residues from the N-terminal region of BBH and the preceding loop in CNA (352-365), and the C-terminal helix of the third EF-hand motif and the following linker region in CNB(115-123). The subsequent binding of CaM leads to displacement of AUTOINHIBITORY_DOMAIN(AID) from the active site and full CN activation

Autoinhibitory domains (AIDs)

407-414 (Autoinhibitory Segment) SS

Target domain

84-284 (Calcineurin-like phosphoesterase domain)

Relief mechanism

Partner binding

Assay

465-487 (Autoinhibitory Domain) SS

Target domain

84-284 (Calcineurin-like phosphoesterase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

2 structures for P63329

Entry ID Method Resolution Chain Position Source
4IL1 X-ray 300 A A/B/C/D 1-492 PDB
AF-P63329-F1 Predicted AlphaFoldDB

2 variants for P63329

Variant ID(s) Position Change Description Diseaes Association Provenance
rs197342160 274 L>M No Ensembl
rs197342160 274 L>V No Ensembl

No associated diseases with P63329

3 regional properties for P63329

Type Name Position InterPro Accession
domain Calcineurin-like phosphoesterase domain, ApaH type 84 - 284 IPR004843
domain Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase 56 - 347 IPR006186
domain PP2B, metallophosphatase domain 41 - 345 IPR041751

Functions

Description
EC Number 3.1.3.16 Phosphoric monoester hydrolases
Subcellular Localization
  • Cytoplasm
  • Cell membrane ; Peripheral membrane protein
  • Cell membrane, sarcolemma
  • Cytoplasm, myofibril, sarcomere, Z line
  • Cell projection, dendritic spine
  • Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle (PubMed:11114196)
  • Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

14 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.
cytoplasmic side of plasma membrane The leaflet the plasma membrane that faces the cytoplasm and any proteins embedded or anchored in it or attached to its surface.
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.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
mitochondrion A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
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.
Schaffer collateral - CA1 synapse A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.
Z disc Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached.

11 GO annotations of molecular function

Name Definition
ATPase binding Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP.
calcium-dependent protein serine/threonine phosphatase activity Catalysis of the reactions: protein serine phosphate + H2O = protein serine + phosphate; and protein threonine phosphate + H2O = protein threonine + phosphate. These reactions require the presence of calcium ions.
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: protein serine/threonine phosphate + H2O = protein serine/threonine + phosphate, dependent on the presence of calcium-bound calmodulin.
cyclosporin A binding Binding to cyclosporin A, a cyclic undecapeptide that contains several N-methylated and unusual amino acids.
enzyme binding Binding to an enzyme, a protein with catalytic activity.
metal ion binding Binding to a metal ion.
phosphoprotein phosphatase activity Catalysis of the reaction: a phosphoprotein + H2O = a protein + phosphate. Together with protein kinases, these enzymes control the state of phosphorylation of cellular proteins and thereby provide an important mechanism for regulating cellular activity.
protein dimerization activity The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
protein serine/threonine phosphatase activity Catalysis of the reaction: protein serine phosphate + H2O = protein serine + phosphate, and protein threonine phosphate + H2O = protein threonine + phosphate.
protein-containing complex binding Binding to a macromolecular complex.

36 GO annotations of biological process

Name Definition
aging A developmental process that is a deterioration and loss of function over time. Aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Aging includes cellular senescence, but is more inclusive. May precede death and may succeed developmental maturation (GO:0021700).
brain development The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
calcineurin-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell by activation of a transcription factor as a consequence of dephosphorylation by Ca(2+)-activated calcineurin. The process begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase with a conserved function in eukaryotic species from yeast to humans. In yeast and fungi, calcineurin regulates stress signaling and cell cycle, and sporulation and virulence in pathogenic fungi. In metazoans, calcineurin is involved in cell commitment, organogenesis and organ development and immune function of T-lymphocytes. By a conserved mechanism, calcineurin phosphatase activates fungal Crz1 and mammalian NFATc by dephosphorylation and translocation of these transcription factors to the nucleus to regulate gene expression.
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+).
calcium ion transport The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
calcium-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via calcium ions.
cardiac muscle hypertrophy in response to stress The physiological enlargement or overgrowth of all or part of the heart muscle due to an increase in size (not length) of individual cardiac muscle fibers, without cell division, as a result of a disturbance in organismal or cellular homeostasis.
cellular response to glucose stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus.
dephosphorylation The process of removing one or more phosphoric (ester or anhydride) residues from a molecule.
excitatory postsynaptic potential A process that leads to a temporary increase in postsynaptic potential due to the flow of positively charged ions into the postsynaptic cell. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC) and makes it easier for the neuron to fire an action potential.
G1/S transition of mitotic cell cycle The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated.
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.
multicellular organismal response to stress Any process that results in a change in state or activity of a multicellular organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating the organism is under stress. The stress is usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation).
negative regulation of calcium ion-dependent exocytosis Any process that stops, prevents, or reduces the frequency, rate or extent of calcium ion-dependent exocytosis.
negative regulation of chromatin binding Any process that stops or reduces the frequency, rate or extent of chromatin binding. Chromatin binding is the selective interaction with chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
negative regulation of dendrite morphogenesis Any process that stops, prevents, or reduces the frequency, rate or extent of dendrite morphogenesis.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of insulin secretion Any process that stops, prevents, or reduces the frequency, rate or extent of the regulated release of insulin.
negative regulation of production of miRNAs involved in gene silencing by miRNA Any process that stops, prevents or reduces the frequency, rate or extent of maturation of miRNAs.
peptidyl-serine dephosphorylation The removal of phosphoric residues from peptidyl-O-phospho-L-serine to form peptidyl-serine.
positive regulation of cardiac muscle hypertrophy Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division.
positive regulation of cardiac muscle hypertrophy in response to stress Any process that activates or increases the frequency, rate or extent of cardiac muscle hypertrophy in response to stress.
positive regulation of cell adhesion Any process that activates or increases the frequency, rate or extent of cell adhesion.
positive regulation of cell migration Any process that activates or increases the frequency, rate or extent of cell migration.
positive regulation of connective tissue replacement Any process that activates or increases the frequency, rate or extent of connective tissue replacement.
positive regulation of DNA-binding transcription factor activity Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of endocytosis Any process that activates or increases the frequency, rate or extent of endocytosis.
positive regulation of gene expression Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
postsynaptic modulation of chemical synaptic transmission Any process, acting in the postsynapse that results in modulation of chemical synaptic transmission.
protein dephosphorylation The process of removing one or more phosphoric residues from a protein.
protein import into nucleus The directed movement of a protein from the cytoplasm to the nucleus.
response to amphetamine 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 an amphetamine stimulus. Amphetamines consist of a group of compounds related to alpha-methylphenethylamine.
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.
transition between fast and slow fiber The process of conversion of fast-contracting muscle fibers to a slower character. This may involve slowing of contractile rate, slow myosin gene induction, increase in oxidative metabolic properties, altered electrophysiology and altered innervation. This process also regulates skeletal muscle adapatation.

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
P48452 PPP3CA Protein phosphatase 3 catalytic subunit alpha Bos taurus (Bovine) SS
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
P48455 Ppp3cc Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform Mus musculus (Mouse) PR
P48453 Ppp3cb Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform Mus musculus (Mouse) SS
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
Q0G819 tax-6 Serine/threonine-protein phosphatase 2B catalytic subunit Caenorhabditis elegans SS
10 20 30 40 50 60
MSEPKAIDPK LSTTDRVVKA VPFPPSHRLT AKEVFDNDGK PRVDILKAHL MKEGRLEESV
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 SYPAVCDFLQ 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